Federal Court  
Cour fédérale  
Date: 20111206  
Dockets: T-644-09  
T-933-09  
Citation: 2011 FC 1486  
Ottawa, Ontario, December 6, 2011  
PRESENT: The Honourable Mr. Justice Boivin  
Docket: T-644-09  
Plaintiff  
BETWEEN:  
APOTEX INC.  
and  
SANOFI-AVENTIS  
Defendant  
Docket: T-933-09  
BETWEEN:  
SANOFI-AVENTIS AND  
BRISTOL-MYERS SQUIBB SANOFI  
PHARMACEUTICALS HOLDINGS  
PARTNERSHIP  
Plaintiffs  
and  
APOTEX INC.  
APOTEX PHARMACHEM INC.  
AND SIGNA SA de CV  
Defendants  
Page: 2  
PUBLIC REASONS FOR JUDGMENT  
Heard: April 18, 19, 20, 21, 26, 27, 28, 29,  
May 3, 4, 5, 9, 10, 11,  
May 16, 17, 18, 19, 24, 25, 30, 31,  
June 1, 13, 14, 15, 2011  
I
Introduction  
Preliminary Observations  
This case concerns the drug clopidogrel bisulfate, sold in Canada under the brand name  
A.  
[1]  
Plavix and commercialized as an anticoagulant that inhibits platelet aggregation activity in the  
blood. Plavix is the subject of Canadian Patent No. 1,336,777 (the ‘777 Patent) issued on August  
22, 1995.  
[2]  
The ‘777 Patent is a selection patent held by Sanofi-Aventis.1 At the heart of this case lies  
the issue of the validity of the ‘777 Patent. Sanofi submits that the ‘777 Patent is valid and that it  
has been infringed by Apotex2 who manufactures and sells generic clopidogrel. Apotex, on the  
other hand, submits that the ‘777 Patent is invalid and that there has accordingly been no  
infringement.  
[3]  
The application leading to the ‘777 Patent was filed in Canada on February 2, 1988. The  
Court observes at the outset that pursuant to s 78.1-78.2 of the current Patent Act, RSC 1985,  
c P-4, as amended, patent applications, such as the one at issue, filed before October 1, 1989 are  
to be dealt with under the provisions of the Patent Act as they read immediately before that date.  
1 In these reasons, the Court will refer to Sanofi-Aventis and Bristol-Myers Squibb Sanofi Pharmaceuticals  
Holdings Partnership collectively, as “Sanofi”.  
2 In these reasons, the Court will refer to Apotex Inc. and Apotex Pharmachem Inc. collectively, as “Apotex”.  
Page: 3  
Thus, references in these Reasons to the Patent Act (referred to as the Patent Act or the Act),  
unless specifically noted otherwise, will be to the Act as it stood immediately prior to October 1,  
1989.  
[4]  
The Court further notes that this proceeding in fact consists of a consolidation of two  
actions. First, there is the impeachment action undertaken by Apotex (T-644-09) and, second, there  
is the infringement action undertaken by Sanofi (T-933-09). The procedural background in which  
each of these actions was initiated is summarized next.  
B.  
Procedural Background  
[5]  
On March 10, 2003, Apotex served upon Sanofi a Notice of Allegation (NOA) under the  
Patented Medicines (Notice of Compliance) Regulations, SOR/93-133 (PMNOC Regulations) for  
the purpose of obtaining a Notice of Compliance (NOC) from the Minister of Health, pursuant to  
section C.08.004 of the Food and Drug Regulations, CRC 1978, c 870. As part of its NOA, Apotex  
alleged that its manufacture and sale of generic clopidogrel bisulfate tablets would not infringe any  
valid claim in the ‘777 Patent.  
[6]  
In response, Sanofi sought an order prohibiting the Minister of Health from issuing a NOC  
to Apotex in respect of generic clopidogrel bisulfate tablets until the expiry of the ‘777 Patent.  
[7]  
By Order dated March 21, 2005, Justice Shore of the Federal Court granted Sanofi’s  
application. As a result of this Order, the ‘777 Patent prevented Apotex from coming to market with  
its generic clopidogrel bisulfate tablets in Canada. The Federal Court of Appeal and the Supreme  
Page: 4  
Court of Canada upheld this Order. Apotex accordingly did not obtain a NOC from the Minister of  
Health.  
[8]  
Following the Order dated March 21, 2005, and related court challenges, the two present  
actions, now consolidated, were commenced as follows: Apotex’ impeachment action dated April  
22, 2009 (T-644-09); and Sanofi’s infringement action dated June 8, 2009 (T-933-09).  
[9]  
In summary, Apotex’ impeachment action seeks a declaration that the claims of the ‘777  
Patent are invalid, void and of no force and effect. Apotex alleges the following grounds of  
invalidity:  
!
!
!
!
!
inutility;  
lack of demonstrated utility/lack of sound prediction;  
obviousness;  
lack of novelty/anticipation;  
double patenting.  
Apotex further seeks a declaration of non-infringement with respect to its generic clopidogrel  
products.  
[10] Conversely, Sanofi’s infringement action seeks a declaration that Apotex has infringed the  
‘777 Patent by manufacturing clopidogrel – containing products in Canada for export to other  
countries, including the United States and that, as a result, Sanofi is entitled to injunctive relief and  
an accounting of profits or damages.3  
3 The Court notes that, initially, the infringement action was also brought against Signa but was discontinued  
against Signa on September 14, 2009.  
Page: 5  
[11] Apotex’ impeachment action and Sanofi’s infringement action were briefed as follows:  
Impeachment Action  
1. Apotex Statement of Claim dated April 22, 2009;  
2. Apotex Amended Statement of Claim dated May 27, 2009;  
3. Sanofi Statement of Defence dated June 8, 2009; and  
4. Apotex Reply dated June 18, 2009.  
Infringement Action  
1. Sanofi Statement of Claim dated June 8, 2009;  
2. Apotex Second Amended Statement of Defence and  
Counterclaim dated December 14, 2010;  
3. Statement of Particulars dated December 2, 2010 to the  
Amended Statement of Defence and Counterclaim of Apotex;  
4. Statement of Particulars dated December 16, 2010 bis;  
5. Sanofi Reply and Defence to Counterclaim dated January 31,  
2010;  
6. Statement of Particulars dated April 8, 2010 in Reply to  
Defence to Counterclaim of Sanofi; and  
7. Apotex Amended Reply to Defence to Counterclaim dated  
April 15, 2011.  
[12] On or about July 15, 2009, Sanofi filed a motion to consolidate the impeachment and  
infringement actions in order for them to be heard together. Apotex indicated its opposition to  
consolidation in its Statement of Defence and Counterclaim and stated that the infringement action  
should be stayed. By Order dated November 2, 2009, Prothonotary Tabib, acting as the Case  
Management Judge, ordered consolidation. She further ordered bifurcation of the damages issues.  
[13] Both actions were accordingly heard together in a trial that commenced on April 18, 2011.  
During the twenty-six (26)-day trial, a total of twenty-three (23) experts and fact witnesses appeared  
before the Court. A brief overview of the experts and fact witnesses’ testimony is included in  
Appendix A.  
Page: 6  
[14] The key questions to be addressed in this proceeding are as follows:  
A) Does Sanofi have standing to bring its infringement action?  
B) Has Apotex infringed the ‘777 Patent?  
C) Is the ‘777 Patent valid?  
[15] As explained in these Reasons, the Court has concluded that:  
A) Sanofi has standing to bring its infringement action;  
B) The ‘777 Patent was infringed by Apotex; and  
C) The ‘777 Patent is invalid.  
[16] As a result, Apotex’ impeachment action is allowed and Sanofi’s infringement action is  
dismissed.  
II  
Table of Contents  
[17] To assist the reader, the Court has compiled a Table of Contents for these Reasons with page  
numbers for each heading.  
Table of Contents  
Paragraph  
I Introduction  
A Preliminary Observations ...............................................................................  
B Procedural Background ..................................................................................  
1
5
II The Table of Contents  
Table of Contents ..................................................................................................  
III NOC Proceedings  
17  
NOC Proceedings ....................................................................................................  
IV Standing  
18  
29  
29  
29  
30  
33  
40  
47  
57  
A The Parties’ Submissions ...............................................................................  
(1) The Position of Apotex .......................................................................  
(2) The Position of Sanofi ........................................................................  
B Subsection 55.1 of the Patent Act – General Principles ................................  
C The BMS/Sanofi Partnership Agreements .....................................................  
D The Evidence before the Court ......................................................................  
E Conclusion on Standing ..................................................................................  
Page: 7  
V Claims Constrution  
A General Principles ...........................................................................................  
B The Hypothetical Person of Ordinary Skill in the Art (POSITA) ................  
C The Patent Specification .................................................................................  
D The Claims at Issue .........................................................................................  
E Claims 1, 3, 10 and 11 .....................................................................................  
F The Limitations of Claims 6 to 9 ....................................................................  
G What is the Meaning of “Medicine of the Invention”? .................................  
H Page 21 of the ‘777 Patent ..............................................................................  
I The Invention described in the ‘777 Patent ....................................................  
J The Construction of the Promise of the Patent ..............................................  
(1) General Principles .................................................................................  
(2) Summary of Expert Evidence ...............................................................  
(3) What Is the Promise of the ‘777 Patent? ...............................................  
K Summary on Claims Construction .................................................................  
58  
64  
81  
95  
96  
102  
108  
119  
133  
141  
141  
147  
158  
182  
VI Infringement – Background  
184  
184  
185  
194  
198  
211  
214  
232  
233  
239  
240  
259  
293  
A Introduction .....................................................................................................  
B General Principles ...........................................................................................  
C Summary of Sanofi’s Case on Infringement .................................................  
D The Evidence before the Court ......................................................................  
(1) Product Claims: Claims 1, 3, 10 and 11 ...............................................  
(2) Process Claims: Claims 6-9 ..................................................................  
E Potential Exemption from Liability ................................................................  
(1) Apotex’ Alleged Experimental Use ......................................................  
F Apotex’ Defences to Infringement .................................................................  
(1) The Limitation Period ...........................................................................  
(2) The Settlement Agreements and Estoppel Defence .............................  
G Conclusion ......................................................................................................  
VII Validity  
294  
295  
303  
306  
306  
312  
323  
330  
331  
336  
336  
339  
358  
358  
363  
363  
A Overbreadth .....................................................................................................  
B Sufficiency .......................................................................................................  
C Anticipation .....................................................................................................  
(1) General Principles ...................................................................................  
(2) The Posters and the Abstracts .................................................................  
(3) The ‘875 Patent .......................................................................................  
(4) The Conclusion in Anticipation .............................................................  
D Double Patenting .............................................................................................  
E Utility ...............................................................................................................  
(1) The Lack of Utility ..................................................................................  
(2) The Demonstrated Utility .......................................................................  
(3) The Utility – Sound Prediction ...............................................................  
(a) The Promise of the ‘777 Patent .....................................................  
(b) The Prediction ................................................................................  
(i) What is the Utility? ...............................................................  
Page: 8  
(ii) The Promise of the Patent ....................................................  
(iii) Prima Facie Reasonable Inference of Utility ......................  
(c) Factual Basis ..................................................................................  
(i) Summary of Chronology ......................................................  
(ii) Important Events in Factual Basis .......................................  
(iii) Draw-Backs in Factual Basis ................................................  
(iv) Conclusion on Factual Basis .................................................  
(d) Sound Line of Reasoning ..............................................................  
(i) Stereochemistry .....................................................................  
(ii) Toxicology ............................................................................  
(iii) Haematology .........................................................................  
(iv) Pharmacology .......................................................................  
(v) Previous Work on Thienopyridine Compounds ...................  
(vi) Extrapolation from Animals to Humans ..............................  
(vii) Conclusion on Line of Reasoning ........................................  
(e) Disclosure .......................................................................................  
(i) Quid Pro Quo – Principles ...................................................  
(ii) Factual Basis .........................................................................  
(iii) Insufficient Disclosure – Essential Elements of Factual Basis  
Missing .................................................................................  
367  
401  
404  
404  
441  
468  
483  
489  
492  
502  
507  
518  
543  
556  
562  
564  
564  
569  
571  
574  
575  
(a) No Reference to Work Done on Ticlopidine ............  
(b) No Reference to PCR 4099 ........................................  
(c) No Reference to Multiple Animal Models used and  
Knowledge of Convulsions .......................................  
(d) No Recognition of Importance of Metabolism .........  
(4) Conclusion on Disclosure ......................................................................  
F Conclusion on Sound Prediction .....................................................................  
578  
580  
584  
585  
VIII Obviousness  
A General Principles ............................................................................................  
B Date of Invention .............................................................................................  
C Common General Knowledge .........................................................................  
(1) The State of the Art of Science ..............................................................  
(2) The ‘875 Patent .......................................................................................  
(3) The Abstracts and Posters at the July 1985 Conference in San Diego  
and the June 1986 Conference in Jerusalem .........................................  
(4) The 1987 FDA Manufacturing Guidelines ...........................................  
(5) The Ariens Article ..................................................................................  
(6) PCR 4099 ................................................................................................  
D Test for Obviousness .......................................................................................  
(1) Identify the Notional “Person Skilled in the Art” ..............................  
(2) Identify the Relevant Common General Knowledge of that Person..  
(3) Identify the Inventive Concept of the Claim in Question or if that  
Cannot Readily be Done, Construe It .................................................  
(4) Identify what, if any, differences exist between the matter cited as  
forming part of the “State of the Art” and the inventive concept of  
587  
591  
601  
605  
608  
615  
629  
639  
645  
648  
649  
650  
653  
Page: 9  
654  
the claim or the claim as construed .....................................................  
(5) Viewed without any knowledge of the alleged Invention as claimed,  
do those differences constitute steps which would have been obvious  
to the Person Skilled in the Art or do they require any degree of  
invention? ............................................................................................  
E “Obvious to Try” Considerations ...................................................................  
(1) Is it more or less self-evident that what is being tried ought to work?  
Are there a finite number of identified predictable solutions known to  
Persons of Ordinary Skill in the Art? .................................................  
(a) Methods to Separate ....................................................................  
(i) What is the “Pasteur Method”? .........................................  
(ii) Would the Person of Ordinary Skill in the Art turn to this  
Chiral HPLC? ....................................................................  
657  
658  
663  
664  
667  
678  
687  
694  
707  
(iii) Conclusion on Method to obtain Separation ....................  
(b) Methods to Obtain Salt Formation .............................................  
(c) Conclusion: “Ought to Work” ....................................................  
(2) What is the extent, nature and amount of effort required to achieve  
the Invention? Are Routine Trials carried out or is the  
Experimentation prolonged and arduous, such that the trials would  
not be considered routine? ..................................................................  
(a) What is “Routine” in separating the enantiomers of PCR 4099  
and obtaining the salts? ............................................................  
(3) Is There a Motive provided in the Prior Art to find the Solution the  
Patent addresses? ................................................................................  
(a) The Motivation to separate: “the Mumblings”of the mid-  
1980’s ........................................................................................  
Event 1: The Thalidomide Disaster ..............................................  
Event 2: The 1985 Japanese Guidelines .......................................  
Event 3: Dr. Kumkumian’s 1986 Speech .....................................  
Event 4: The 1987 FDA Guidelines Document and the  
709  
709  
721  
722  
725  
727  
729  
Stereoisomer’s Committee .............................................  
733  
735  
738  
741  
743  
750  
752  
783  
Event 5: The 1989 Nature Article and the Pressure for New Drugs  
Event 6: Joint Venture Partner asking about Data on Enantiomer  
Event 7: The 1992 FDA Policy In Force ......................................  
(b) Summary ...................................................................................  
(c) Conclusion “Motivation” ..........................................................  
(4) Actual Course of Conduct that Culminated in Invention ..................  
(5) Conclusion on Obviousness ...............................................................  
IX Overall Conclusions  
Conclusion .......................................................................................................  
785  
Page: 10  
III  
NOC Proceedings  
[18] As noted earlier, the parties’ dispute regarding the ‘777 Patent was the subject of a NOC  
proceeding. Given the circumstances, the Court considers it apposite to provide a brief overview of  
these NOC proceedings.  
[19] Essentially, NOC proceedings consist of a summary procedure for assessing the validity of a  
Canadian patent. Such proceedings are initiated by way of application to the Federal Court of  
Canada (Sanofi-Synthelabo Canada Inc. v Apotex Inc., 2005 FC 390, 39 CPR (4th) 202). In  
particular, there is no viva voce testimony from witnesses, and the evidence is accordingly limited to  
a documentary record. Significantly, the PMNOC Regulations do not allow any determinative  
findings on the validity of the patent per se; the only conclusion to be drawn in the context of NOC  
proceedings is whether the allegations of patent invalidity are “justified” or “not justified”.  
[20] Furthermore, the PMNOC Regulations do not displace the right of a patent holder to bring  
an action for infringement, an interested person to challenge the validity of a patent in an action for  
impeachment (Pharmacia Inc. v Canada (Minister of National Health & Welfare) (1994), [1995] 1  
FC 588, 58 CPR (3d) 209 (FCA) at 217; Bristol-Myers Squibb Co. v Canada (Attorney General),  
2005 SCC 26, 39 CPR (4th) 449 at paras 11-12).  
[21] As part of the NOC proceedings initiated by Apotex, it was alleged by Apotex that a NOC  
should be issued because generic clopidogrel bisulfate did not infringe the ‘777 Patent. In particular,  
Apotex maintained that the ‘777 Patent was invalid on grounds of obviousness, anticipation and  
double patenting.  
Page: 11  
[22] As noted earlier, Apotex was not successful in obtaining a NOC. Justice Shore, the  
Applications Judge, rejected all three (3) of Apotex’ allegations of invalidity on the basis that these  
allegations were not justified.  
[23] Apotex appealed the decision of Justice Shore and, on December 22, 2006, the Federal  
Court of Appeal upheld this decision and accordingly dismissed Apotex’ appeal (Sanofi-Synthelabo  
Canada Inc. v Apotex Inc., 2006 FCA 421, 59 CPR (4th) 46).  
[24] Justice Noël, writing for a unanimous Federal Court of Appeal, concluded that Apotex had  
not shown, on a balance of probabilities, that Justice Shore had committed any reviewable errors in  
arriving at the conclusions on obviousness, anticipation and double patenting.  
[25] Thereafter, Apotex appealed to the Supreme Court of Canada. On November 6, 2008, in  
Apotex v Sanofi-Synthelabo Canada Inc., 2008 SCC 61, 69 CPR (4th) 251 (SCC Plavix), the  
Supreme Court of Canada, in a unanimous judgment written by Justice Rothstein, dismissed  
Apotex’ appeal, again on the issues of obviousness, anticipation and double patenting. In its  
judgment, the Supreme Court of Canada modified the legal tests for the law of obviousness and  
anticipation. A review of the relevant legal principles will be considered later in this decision.  
[26] In the context of the present case, Sanofi relied extensively on the decision of the Supreme  
Court of Canada in the NOC proceedings. However, the NOC proceedings and the fact conclusions  
they may have yielded are of limited assistance when, as here, the evidence adduced and the issues  
differ considerably from those presented in the course of the NOC proceedings. Indeed, unlike the  
Page: 12  
NOC proceedings, the present impeachment and infringement actions, at trial, involved viva voce  
testimony from nine (9) experts and fourteen (14) fact witnesses. Furthermore, these experts and  
fact witnesses were heard on a broader range of issues than those considered as part of the NOC  
proceedings. In particular, many were heard on the issue of sound prediction which, as seen later, is  
a central question before the Court. Yet the issue of sound prediction was not addressed as part of  
the NOC proceedings and there was accordingly no evidenciary record on that issue.  
[27] On the issues of obviousness and anticipation, it is equally clear that the evidentiary record  
before the Federal Court of Canada, the Federal Court of Appeal, and the Supreme Court of Canada  
differed significantly from the record before the Court. Thus, whilst the Court recognizes that the  
legal principles and the questions of law decided by the Supreme Court of Canada in the NOC  
proceedings must necessarily be followed, the Court is not, however, bound by the factual findings  
made in the context of the NOC proceedings because the evidence is not necessarily the same.  
Hence, the NOC proceedings, whilst instructive, are not fact-determinative. As further noted by the  
Federal Court of Appeal, “factual findings are derived from the evidence that is before the court in  
the particular proceeding” and it is “incumbent upon the judge to arrive at his findings on the basis  
of the evidence that was before him” (Ratiopharm Inc. v Pfizer Ltd., 2010 FCA 204, 87 CPR (4th)  
185, at paras 25 and 26).  
[28] It follows that NOC proceedings do not constitute res judicata (Ratiopharm Inc. v Pfizer  
Ltd., 2009 FC 711, 76 CPR (4th) 241, at para 18; Eli Lilly Canada Inc. v Novopharm Ltd., 2009 FC  
235, 73 CPR (4th) 253). To put it another way, NOC proceedings are not the gospel.  
Page: 13  
IV  
Standing  
A.  
The Parties’ Submissions  
(1) The Position of Apotex  
[29] Apotex submits that one of the plaintiffs in this case, namely Bristol-Myers Squibb Sanofi  
Pharmaceuticals Holding Partnership (the Partnership), has no standing to bring the present action  
to the extent it relates to any acts of infringement alleged to have taken place prior to June 12, 2007,  
the date on which the Amendment to Clopidogrel Intellectual Property License and Supply  
Agreement (the Amended IP Agreement) was entered into between Sanofi and the Partnership. It is  
Apotex’ position that the Partnership had no explicit licence prior to the Amended IP Agreement  
and that, furthermore, such an amendment cannot be applied to confer rights retroactively. Apotex  
argues that the Partnership is not the active entity that carries on in the foreign jurisdictions at issue  
and Apotex also argues that the Partnership does not operate in Canada. This, according to Apotex,  
bars the Partnership from seeking recovery in the form of damages in the circumstances.  
(2) The Position of Sanofi  
[30] In response, Sanofi asserts that, on the basis of its ‘777 Patent, there can be no question that  
it has standing to sue for infringement and obtain a remedy. As for the Partnership, Sanofi submits  
that it is an exclusive licensee under the ‘777 Patent and that the Partnership consequently has  
standing to sue for infringement and obtain a remedy as described in ss 55(1) of the Patent Act.  
[31] More particularly, Sanofi argues that the Partnership is a “person claiming under” a patentee  
as stated in ss 55(1) of the Patent Act because the Partnership is assessing a right under the ‘777  
Patent and that can be traced right back to the patentee. According to Sanofi, exclusive and non-  
Page: 14  
exclusive licensees, implied or oral, qualify as a “person claiming under” under a patentee (Jay-Lor,  
below).  
[32] In this regard, Sanofi emphasizes that the Partnership has been given an explicit right to use  
and exploit the subject matter of the ‘777 Patent and clopidogrel bisulfate.  
B.  
Subsection 55(1) of the Patent Act – General Principles  
[33] The term “patentee” is defined in s 2 of the Patent Act to mean “the person for the time  
being entitled to the benefit of a patent”. Because the patentee has monopoly over his patented  
invention, he may on this basis assign, licence or give a right to use his patent either exclusively or  
non-exclusively, in whole or in part. Significantly, ss 55(1) of the Patent Act provides a damages  
remedy and hence standing to claim damages not only to the patentee but also to “all persons  
claiming under the patentee”. Subsection 55(1) provides as follows:  
55. (1) A person who infringes 55. (1) Quiconque viole un  
a patent is liable to the  
patentee and to all persons  
claiming under him for all  
damages sustained by the  
patentee or by any such  
person, by reason of the  
infringement.  
brevet est responsable, envers  
le breveté et envers toute  
personne se réclamant du  
breveté, de tous dommages-  
intérêts que cette violation a  
fait subir au breveté ou à cette  
autre personne.  
[34] The question of who qualifies as a person claiming under a patentee pursuant to ss 55(1) of  
the Patent Act has been analyzed numerous times by Canadian courts. In the 1972 case, American  
Cyanamid Company v Novopharm Limited, [1972] FC 739 (FCA), the Federal Court of Canada  
enlarged the meaning of “persons claiming under” when it held that a non-exclusive licensee of a  
patent is a person claiming under the patentee within the meaning of ss 55(1) of the Patent Act.  
Page: 15  
[35] Along the same lines, in Armstrong Cork Canada Ltd. v Domco Industries Ltd., [1982] 1  
SCR 907, 66 CPR (2d) 46, at p 912, the Supreme Court of Canada adopted the comments of Fry  
L.J. at p 470, in Heap v Hartley, (1889) 42 Ch D 461:  
[…] An exclusive license is only a license in one sense; that is to say,  
the true nature of an exclusive license is this. It is a leave to do a  
thing, and a contract not to give leave to anybody else to do the same  
thing. But it confers like any other license, no interest or property in  
the thing. […]  
[36] Another leading case in this regard is Signalisation de Montréal Inc. v Services de Béton  
Universels Ltée (FCA), [1993] 1 FC 341, 46 CPR (3d) 199, where the Federal Court of Appeal  
analyzed the issue of the rights of someone other than the patentee to maintain an action for  
infringement. In so doing, the Federal Court of Appeal considerably enlarged the pool of “persons  
claiming under the patentee”. It held at pp 210-211 that:  
[…] a person “claiming under” the patentee is a person who derives  
his rights to use the patented invention, at whatever degree, from the  
patentee. The right to use an invention is one the monopoly to which  
is conferred by a patent. When a breach of that right is asserted by a  
person who can trace his title in a direct line back to the patentee, that  
person is “claiming under” the patentee. It matters not by what  
technical means the acquisition of the right to use may have taken  
place. It may be a straightforward assignment or a licence. It may, as  
I have indicated, be a sale of an article embodying the invention. It  
may also be a lease thereof. What matters is that the claimant asserts  
a right in the monopoly and that the source of that right may be  
traced back to the patentee. […]  
[37] More recently, Justice Snider in the case of Laboratoires Servier v Apotex Inc., 2008 FC  
825, 67 CPR (4th) 241, at para 77, found that “[t]he ability of a party to claim under a patentee does  
not necessarily require the existence of an express licence”. She added that “[w]here no express  
Page: 16  
licence exists, each case will be determined on its facts to determine whether an implied licence or  
other right exists that gives rise to a claim “under the patentee”.  
[38] In addition, Justice Snider in Servier, above, at para 70, provided the following guidance:  
[70] The test for who qualifies as a person claiming under a patentee  
is not simply whether the patentee has consented to the person being  
joined as a plaintiff in an action; nor is it enough to demonstrate that  
two parties are related. In each case, the facts must demonstrate a  
credible and legally sufficient basis for claiming under a patentee  
(Jay-Lor International Inc. v. Penta Farm Systems Ltd., (2007), 59  
C.P.R. (4th) 228 at paras 31, 36 (F.C.) [Jay-Lor]).  
[Emphasis added]  
[39] In light of these principles, the Court now turns to the BMS/Sanofi Partnership Agreements  
entered into between Sanofi and the Partnership.  
C.  
The BMS/Sanofi Partnership Agreements  
[40] The Partnership arose from the discovery of clopidogrel and irbesartan, two promising  
drugs. Because Sanofi had very little presence in the United States and Canada, it turned to Bristol-  
Myers Squibb (BMS) to create a partnership in order to commercialize the compounds on a  
worldwide basis. Sanofi and BMS accordingly entered into a Development Agreement in 1993, as  
well as a series of subsequent agreements including a Partnership Agreement, an Alliance Support  
Agreement (Territory A and B), a Product Know-How Licence Agreement and a Clopidogrel  
Intellectual Property License and Supply Agreement, all of which are dated January 1, 1997.  
Page: 17  
[41] In 2007, the parties decided to revise the initial Clopidogrel Intellectual Property License  
and Supply Agreement they had signed in 1997. This revised agreement was meant to address the  
needs of the alliance as the products were moving closer to commercialization and it included  
revisions to […] of the initial agreement listing the patent at issue. Thus, an Amendment to  
Clopidogrel Intellectual Property License and Supply Agreement was signed on December 6, 2007.  
[42] The Court observes that contractual arrangements regarding the Partnership were structured  
around two territories, commonly referred to as Territory A and B. Territory B covers the United  
States, Canada, Mexico, South America, Australia and New Zealand, whereas Territory A includes  
Europe, Africa, the Middle East and Asia. Two territory partnerships were accordingly formed in  
order to manage central expenses, such as marketing, research and development and royalties, and  
to supply the finished product to the individual countries. At the country level, agreements either to  
co-promote or to co-market were also put in place.  
[43] The Court further notes that the Product Know-How Licence Agreement confers rights to  
either party in the Partnership with regards to all technical data, information, material and other  
know-how that relates to the formulation of the products that are developed under the Development  
Agreement.  
[44] As for the Clopidogrel Intellectual Property License and Supply Agreement (1997) as well  
as the Amended Agreement (2007), it grants an exclusive licence to the Partnership in the following  
terms:  
[…] [omitted] .  
Page: 18  
[45] [omitted] .  
[46] Against this background, the Court now turns to the evidence put before it in connection  
with the rights conferred to the Partnership.  
D.  
The Evidence before the Court  
[47] During the trial, Dr. Thierry Saugier, Vice-President Alliance and Partnership at Sanofi-  
Aventis, was called by Sanofi to testify as to the standing of the Partnership. Dr. Saugier testified  
that, since April 2006, he has managed group of alliances for Sanofi-Aventis, including the alliance  
referred to the Territory B Partnership and the Territory A Partnership.  
[48] In particular, Dr. Saugier testified that, in order to structure the alliance, Sanofi granted an  
exclusive licence for clopidogrel to the Partnership, as can be seen in the Partnership Agreements  
which are still in effect today. The various agreements produced into evidence indeed support Dr.  
Saugier’s oral testimony as to the rights granted thereunder.  
[49] [omitted]:  
Q. [omitted]?  
A. [omitted].  
Q. [omitted]?  
A. [omitted].  
Q. [omitted]?  
A. [omitted].  
Q. [omitted]?  
A. [omitted].  
[50] [omitted]:  
Page: 19  
Q. [omitted]?  
A. [omitted].  
Q. [omitted]?  
A. [omitted].  
Q. [omitted]?  
A. [omitted].  
Q. [omitted]?  
A. [omitted].  
Q. [omitted]?  
A. [omitted].  
Q. [omitted]?  
A. [omitted].  
Q. [omitted]?  
A. [omitted].  
Q. [omitted]?  
A. [omitted].  
[51] [omitted].  
[52] [omitted].  
[53] [omitted].  
[54] [omitted]:  
[omitted].  
[55] The Court believes that such a list could not, on a practical point of view, be amended each  
time a development occurred in connection with products under research or in a process of a patent  
application. The terms and scope of the agreement at issue are such that […] must be interpreted to  
encompass newly developed compounds. To conclude otherwise would fly in the face of the very  
purpose of the Partnership Agreements, which was to allow the Partnership to carry out all activities  
Page: 20  
related to the development, manufacturing, sourcing and commercialization of clopidogrel in the  
specified territory known as Territory B, would otherwise be defeated.  
[56] Finally, the Court recalls that counsel for Apotex questioned Dr. Saugier in connection with  
the absence of manufacturing facilities, employees and registered place of business in Canada in  
order to demonstrate the lack of standing. In light of the breadth of the Partnership Agreements, the  
Court finds this line of questioning to be of no assistance for the purposes of the standing issue.  
E.  
Conclusion on Standing  
[57] In sum, considering the broad meaning of “persons claiming under” a patentee as referred to  
under ss 55(1) of the Patent Act, and based on the Court’s review of the Partnership Agreements  
and the testimony given in that regard, the Court finds that the Partnership has a “credible and  
legally sufficient basis” for claiming under a patentee in the circumstances. Indeed, the evidence  
clearly shows that the Partnership was granted an exclusive licence for clopidogrel products through  
the various Agreements as of 1997. It follows that the Partnership has standing to bring the action at  
issue for any infringement that it alleges to have occurred prior to December 6, 2007.  
V
Claims Construction  
A.  
General Principles  
[58] In a patent case such as the one at issue, the Court must first construe the claims of the  
patent in accordance with the principles of claims construction established by the caselaw  
(Whirlpool Corp. v Camco Inc., 2000 SCC 67, 9 CPR (4th) 129; Novopharm Ltd. v Janssen-Ortho  
Page: 21  
Inc., 2007 FCA 217, 59 CPR (4th) 116; Canada (Attorney General) v Amazon.com, Inc., 2011 FCA  
328, [2011] FCJ No 1621).  
[59] The Court observes that claims construction is a question of law and must be addressed with  
a purposive approach in order “to achieve fairness and predictability and to define the limits of the  
monopoly” (Dimplex North America Ltd. v CFM Corp., 2006 FC 586, 54 CPR (4th) 435, at para 49,  
aff'd 2007 FCA 278, 60 CPR (4th) 277). In so doing, the Court is required to read the patent claims  
with “a mind willing to understand” (Whirlpool, above).  
[60] Conceptually, the claims construction analysis focuses on what a hypothetical person of  
ordinary skill in the art (POSITA) would have understood the patent to claim (Whirlpool, above, at  
paras 45, 53). This, in turn, requires that the Court first determine the requisite skills and expertise  
for the POSITA (Aventis Pharma Inc. v Apotex Inc., 2005 FC 1283, 43 CPR (4th) 161; Apotex Inc. v  
Syntex Pharmaceuticals International Ltd, [1999] FCJ No 548, 166 FTR 161, at para 38, (QL)  
(FCTD)).  
[61] Furthermore, as the patent should be read as a whole, the claims should be read in light of  
the description in the specification, assisted by experts as to the meaning of technical terms used  
therein (Shire Biochem Inc. v Canada (Minister of Health), 2008 FC 538, 328 FTR 123, at para 22;  
Whirlpool, above, at para 45).  
[62] The Court further recalls that, because the ‘777 Patent was issued under the old Patent Act,  
all claims are to be construed as of the date the patent was granted and issued (Pfizer Canada Inc. v  
Page: 22  
Canada (Minister of Health), 2005 FC 1725, 285 FTR 1, at para 36). In the case of the ‘777 Patent,  
the relevant date is August 22, 1995.  
[63] With these general principles of claims construction in mind, the Court now turns to its  
assessment of the POSITA.  
B.  
The Hypothetical Person of Ordinary Skill in the Art (POSITA)  
[64] In assessing the hypothetical POSITA, the Court must define the person or group to whom  
the ‘777 Patent is addressed. This person is obviously not a real person. As explained by Justice  
Hughes in Merck & Co v Pharmascience Inc., 2010 FC 510, 85 CPR (4th) 179, at para 42: “[T]hat  
person is to be unimaginative, but that does not mean that the person is slow-witted or graduated (if  
at all) at the bottom of the class. Nor is the person the gold medalist who graduated at the top of the  
class. That person is the average person in the group. Just as a “reasonable man” is expected to be  
reasonable, the POSITA is expected to possess the ordinary skill in the art”.  
[65] The Supreme Court of Canada considered such a person in Whirlpool, above, at para 74,  
where Justice Binnie for the Court wrote that the POSITA refers to the hypothetical “ordinary  
worker” who is reasonably diligent in keeping up with advances in the field to which the patent  
relates.  
[66] In Merck & Co v Pharmascience Inc., above, at para 35, Justice Hughes further referred to  
submissions made by the Canadian Group of AIPPI (Association internationale pour la Protection  
Page: 23  
de la Propriété intellectuelle) and to a summary under Canadian law as to what a POSITA is  
understood to be:  
35. …  
Q.213 Summary  
In Canada, the “person of ordinary skill in the art” is the hypothetical  
person to whom the patent is addressed. This may be a single individual  
or a group representing different disciplines, depending on the nature of  
the invention. The person of ordinary skill in the art is deemed to be  
unimaginative and uninventive, but at the same time is understood to  
have an ordinary level of competence and knowledge incidental the field  
to which the patent relates (i.e. the common general knowledge) and to  
be reasonably diligent in keeping up with advances. The common  
general knowledge is that knowledge generally known by persons  
skilled in the relevant art at the relevant time. Accordingly, it can include  
knowledge passed amongst people in the field, including information  
that is not in published form. Likewise, not everything that has been  
published is within the common general knowledge.  
Evidence Adduced by the Experts on the POSITA  
[67] The Court heard from numerous experts on behalf of both Apotex and Sanofi in connection  
with the POSITA, as set forth next.  
Apotex’ Experts  
[68] Dr. Hirsh stated that the ‘777 Patent is addressed to persons skilled in clinical  
medicine/haematology, biochemistry, chemistry, pharmacology, toxicology, and pharmacy.  
[69] Dr. Adger opined that the ‘777 Patent is addressed to a person with skills in chemistry,  
haematology, toxicology, pharmacology and pharmaceutical formulations. In regard to the issues of  
chemistry, the person would have post-graduate level training in organic chemistry with special  
Page: 24  
focus in synthetic or medicinal chemistry and/or a combination thereof. Such a person would also  
have several years of experience in synthesizing organic pharmaceutical compounds, including  
resolving racemic drugs or otherwise making single enantiomer medicines. This person would  
understand basic concepts of stereochemistry, would be generally familiar with techniques for the  
analysis and separation of enantiomers and would have familiarity with enantiomeric  
pharmaceutical drugs.  
[70] Dr. Levy submitted that the ‘777 Patent covers areas of chemistry, medicine, haematology  
and platelets, pharmacology, toxicology and pharmaceutical formulation. Regarding areas of  
pharmacology, the person the ‘777 Patent addresses is a Ph.D. level pharmacologist with at least  
several years of working as a pharmacologist.  
[71] Dr. Sanders indicated that the patent addresses issues of chemistry, pharmacology,  
mechanisms of platelet aggregation and thrombosis, toxicology, pharmaceutical formulation, and  
medicine. He further opined that the patent engages a variety of disciplines, one of which is  
toxicology. With regard to toxicology, the person to whom the patent is addressed is a trained  
toxicologist having a Ph.D. in pharmacology or toxicology together with two or three years of  
experience in the toxicology of pharmaceutical products. The person could also have a Master’s  
degree in these fields with about five years of practical experience or a bachelor’s degree in these  
fields with approximately ten years of experience.  
Page: 25  
Sanofi’s Experts  
[72] Dr. Byrn stated that the ‘777 Patent is primarily addressed to an ordinary person working in  
the synthesis or formulation of pharmaceutical compounds. Such a person would have at least a  
bachelor’s degree in chemistry or a related discipline and several years of experience working in a  
pharmaceutical laboratory synthesizing or formulating pharmaceutical compounds.  
[73] Dr. Rodricks agreed that the ‘777 Patent is directed to many different areas including  
chemistry, toxicology, pharmacology, salts and pharmaceutical compositions. His understanding is  
that a person skilled in the art as it relates to the toxicology aspects would have an advanced degree  
in toxicology or pharmacology, or in biochemistry, or a related subject with additional specific  
training and experience in the area of toxicology and drug safety, including the evaluation and  
interpretation of toxicology data.  
[74] Dr. Davies opined that a person of ordinary skill in the art is a pharmaceutical chemist  
having a bachelor’s or doctoral degree in chemistry or a related discipline and several years of  
experience working in a pharmaceutical laboratory synthesizing drug compounds. The  
understanding of the invention of the ‘777 Patent is the knowledge and experience of  
stereochemistry, chiral separation, and drug discovery are crucial to the understanding of the  
invention of the ‘777 Patent. Therefore, a pharmaceutical chemist with experience in  
stereochemistry has this background. Dr. Davies disagreed that toxicologists and medical doctors  
are persons to whom the ‘777 Patent is addressed.  
Page: 26  
[75] Dr. Shebuski indicated that the ‘777 Patent is primarily directed to a pharmaceutical  
chemist, but also to a pharmacologist and toxicologist to the extent they are asked by the  
pharmaceutical chemist to conduct testing relating to the compound that the chemist has made.  
The Court’s Findings on the POSITA  
[76] As gleaned from the above, Apotex advances that the POSITA includes not only a  
pharmaceutical chemist but also a toxicologist, haematologist and medical doctor. Sanofi, on the  
other hand, argues that the POSITA is a pharmaceutical chemist.  
[77] While the Court agrees with Sanofi and Dr. Davies that the ‘777 Patent is addressed to a  
pharmaceutical chemist because experience in stereochemistry, chiral separation and drug discovery  
is key to understanding the ‘777 Patent, the Court cannot agree to an interpretation of the POSITA  
limited to a pharmaceutical chemist. This would amount to providing the pharmaceutical chemist  
with the “loudest voice” (Merck and Co v Pharmascience Inc., above). The Court considers that  
there is more to the understanding of the ‘777 Patent than possessing merely the skill of  
pharmaceutical chemistry. The ‘777 Patent contains a variety of aspects as emphasized by both Dr.  
Levy for Apotex and Dr. Rodricks for Sanofi. In that context, the POSITA has to be approached as  
a team of persons as opposed to a single person with all the skills.  
[78] More particularly, the ‘777 Patent addresses identity and chemical structure of the  
enantiomer known as the dextro-rotatory enantiomer of methyl alpha-5 (4,5,6,7-tetrahydro (3,2-C)  
thieno pyridyl) (2-chlorophenyl)-acetate and its racemate and the levo-rotatory enantiomer. The  
patent discusses a method for isolating the two enantiomers from the racemic mixture, methods of  
Page: 27  
forming the pharmaceutically-acceptable salts of the two enantiomers and methods of preparing  
pharmaceutical compositions.  
[79] The ‘777 Patent also addresses comparative pharmacological and toxicological properties of  
the two enantiomers and the racemate. It further makes reference to their respective ability to be  
used as medicines in pharmaceutical compositions of particular dosage strengths with respect to the  
mechanisms of arterial and venous thrombosis that are to be used in treatment of platelet disorders  
due to extracorporeal blood circuits and the complications of atheroma.  
[80] The Court accordingly concludes that the hypothetical person skilled in the art (POSITA) in  
the case at bar consists of a number of skilled individuals; holding a Ph.D in pharmaceutical  
chemistry; with several years of experience working in the fields of pharmacology and toxicology;  
and having good general knowledge of haematology and medicine.  
C.  
The Patent Specification  
[81] Having established the POSITA, the Court must now consider the patent specification at  
issue.  
[82] The Court notes that the ‘777 Patent is a selection patent. It begins, at page 1, with a general  
statement of the invention relating to the compound, its process, its preparation and its composition  
as follows:  
The present invention relates to the dextro-rotatory enantiomer of methyl  
alpha-5 (4,5,6,7-tetrahydro (3,2-c) thieno pyridyl) (2-chorophenyl)-  
acetate, a process for its preparation and pharmaceutical compositions  
containing it.  
Page: 28  
[83] The patent further specifies that the compound of the invention contains a pyridine ring, a  
phenyl ring, a chiral center and an H-bonding group. The compound of the invention corresponds to  
the following formula:  
[84] At page 1 of the Patent, at line 25, the inventors distinguish their invention from the prior art  
and further specify at line 29 that the invention also relates to salts:  
In an unexpected manner only the dextro-rotatory enantiomer Id  
exhibits a platelet aggregation inhibiting activity, the levo-rotatory  
enantiomer Il being inactive. Moreover, the inactive levo-rotatary  
enantiomer Il is the less well tolerated of the two enantiomers.  
The invention also relates to the addition salts of the compounds of  
formula (Id) with pharmaceutically acceptable mineral or organic acids.  
[85] At page 2 of the Patent, the inventors begin a discussion on salts. They mention that some of  
the salts of the dextro-rotatory enantiomer Id are sometimes difficult to handle on an industrial scale  
because they precipitate in an amorphous form and/or they are hygroscopic. However, at page 2, at  
line 10, it is said that salts have been found that crystallize easily, are not hygroscopic and have  
good water solubility:  
Page: 29  
Among the mineral and organic acid salts of the dextro-rotatory  
isomer of the compound of Formula (Id) salts have been found  
which crystallize easily, are not hygroscopic and are sufficiently  
water-soluble as to make their use as active medicinal principles  
particularly advantageous.  
[86] Specifically, the inventors explain that “[t]he present invention thus relates more particularly  
to the hydrogen sulfate, the taurocholate and the hydrobromide of the dextro-rotatory enantiomer of  
methyl alpha-5 (4,5,6,7-tetrahydro (3,2-c) thieno pyridyl) (2-chlorophenyl)-acetate”.  
[87] The Court notes that beginning at the bottom of page 7 through to page 11, the inventors go  
on to provide examples to the reader to illustrate the invention.  
[88] Thereafter, at page 12, the Patent discloses the results of a pharmacological study and sets  
forth another advantage of the invention:  
A description will now be given of the results of this study which  
demonstrates another advantage of the invention, namely that the  
salts of the dextro-rotatory isomer have a better therapeutic index  
than the salt of the racemic mixture; in fact, the levo-rotatory isomer  
exhibits almost no platelet aggregation inhibiting activity and its  
toxicity is markedly higher than that of its dextro-rotatory  
homologue.  
[89] The result of the pharmacological study is described in four (4) distinct Tables:  
!
Table I, at page 14, relates to platelet aggregation inhibiting  
activity assay using ADP. According to the patent, the data  
“demonstrate that the levo-rotatory isomer is inactive and that  
the dextro-rotatory isomer [clopidogrel] is at least as active as  
the racemate”.  
!
Table II, at page 16, relates to platelet aggregation inhibiting  
activity assay using collagen, the results “demonstrate again that  
only the dextro-rotatory isomer [clopidogrel] is active whereas  
the salts have comparable activities”.  
Page: 30  
!
!
Table III, at page 18, relates to the antithrombotic test.  
According to the patent, the results “show that the levo-rotatory  
isomer is inactive in this test, in contrast to the dextro-rotatory  
isomer [clopidogrel] and the racemate”.  
Lastly, Table IV, at page 19, relates to the LD50 test. According  
to the patent, the results “show on the one hand that the toxicity  
of the racemic mixture is similar to that of the levo-rotatory  
isomer whereas the dextro-rotatory isomer [clopidogrel] is  
markedly less toxic, and, on the other hand, that the toxicity  
depends on the nature of the acid used to form the salt”.  
[90] Following the four (4) above-described tables, the ‘777 Patent at pages 12 to 19 sets out  
three (3) different tests performed on female rats:  
Test no. 1: the compounds were administered to groups of five  
female rats of the CD-COBS strain and then blood samples were  
taken from the animals after the compounds have been metabolized  
in the rats for two hours. Platelet rich plasma was then isolated and  
aggregation is induced either with ADP (the ‘777 Patent, Table 1) or  
collagen of type 1 (the ‘777 Patent, Table II). Aggregation of the  
platelets was then monitored and a curve is generated to represent a  
change in optical density. This type of test is known as an ex vivo test  
because although compounds were administered to animals and  
blood removed, the test was performed outside of living animals. The  
results of the tests are reported in Tables I and II.  
Test no. 2: this test was inspired by the test developed by Kumada in  
1980 (Kumada et al. “Experimental model of venous thrombosis in  
rats and effect of some agents” 1980, Thrombosis Research 18; 189-  
203). It is an in vivo test and was performed by inserting a steel wire  
into the inferior vena cava of a rat. After a period of time a  
thrombosis develops on the wire and the weight of the thrombus is  
measured in untreated rats and those treated with the test compound.  
The difference in weight of thrombosis formed with and without the  
administration of various drugs is used as a measure of the  
antithrombotic of the test compound. It is also known as the  
AV/Shunt model. The results of this test are presented in Table III.  
Test no. 3: The third test was the LD50 test. This test is an acute  
toxicity test where the measured endpoint of the experiment is death  
Page: 31  
in 50% of the animals treated. The lethality is a response that occurs  
at very high doses with a single administration. The results are in  
Table IV.  
[91] Then at page 20 at line 4, the Patent explains how the invention can be used:  
The medicine of the invention can be made available for oral  
administration in the form of tablets, sugar-coated tablets, capsules,  
drops, granules or a syrup. It can also be made available for rectal  
administration in the form of suppositories or for parenteral  
administration in the form of an injectable solution.  
[92] Further, at page 20 at lines 15 to 35, the Patent makes reference to some pharmaceutical  
formulations of the medicine of the invention for tablets, sugar-coated tablets, capsules, injectable  
solution and suppositories.  
[93] Finally, at page 21, on which there is a sole paragraph, reference is made to medicine of the  
invention as follows:  
On account of its interesting inhibitory properties towards platelet  
aggregation and its interference in the mechanism of formation of  
arterial and venous thromboses, the medicine of the invention can be  
usefully administered in the treatment and prevention of platelet  
disorders due to extracorporeal blood circuits or the consequence of  
complications in atheroma.  
[94] The Court now turns to the Patent claims at issue.  
D.  
The Claims at Issue  
[95] By way of a preliminary observation, the Court notes that the ‘777 Patent has eleven (11)  
claims and they are set forth at pages 22 and 23 thereof. These claims can be grouped as follows:  
Page: 32  
!
!
!
Claims 1 to 5 relate to clopidogrel and its salts;  
Claims 6 to 9 relate to the process of making clopidogrel;  
Claims 10 and 11 relate to the pharmaceutical compositions.  
The Court observes that there are a number of areas of disagreement between Apotex and Sanofi  
which are the following:  
!
!
!
!
!
The Purity of Claims 1, 3, 10, 11;  
The Limitations of Claims 6 to 9;  
What is the meaning of “Medicine of the Invention”;  
Page 21 of the ‘777 Patent; and  
The Invention described in the ‘777 Patent.  
E.  
Claims 1, 3, 10 and 11  
[96] The only relevant issue with respect to the construction of Claims 1, 3, 10 and 11 concerns  
the degree of enantiomeric purity of the clopidogrel referred to in these claims. Apotex submits that  
the disclosure of the racemate discloses clopidogrel that is 50% pure. The ‘777 Patent contains no  
purity limitation.  
[97] The ‘777 Patent at page 7 discusses the determination of the enantiomer (optical) purity of  
the dextro-enantiomer and the levo-enantiomer. It further states that, under the conditions described,  
the optical purity is at least equal to 96% for the dextro-rotatory enantiomer and at least equal to  
98% for the levo-rotatory enantiomer.  
[98] From this observation, the experts for both parties (Dr. Byrn, Dr. Hirsh and Dr. Adger)  
agreed that the purity of the clopidogrel claimed in the ‘777 Patent - although not 100% pure - is  
“substantially pure”.  
Page: 33  
[99] Furthermore, Dr. Hirsh testified that the number of at least equal to 96% for the dextro-  
rotatory enantiomer, and 98% for the levo-rotatory enantiomer and with respect to the optical purity  
is relative to the limit of detection.  
[100] On this basis, and given that the independent claim has been construed as “substantially  
pure”, the Court concludes that the dependent claims should also be construed as “substantially  
pure”.  
[101] Hence, the Court finds that a POSITA would conclude that Claim 3 encompasses  
“substantially pure” hydrogen sulfate salt of clopidogrel.  
F.  
The Limitations of Claims 6 to 9  
[102] As mentioned above, Claim 6 relates to the general process of making clopidogrel and its  
pharmaceutically acceptable salts. This general process can be summarized as follows:  
!
!
formation of a salt of the racemate with an optically active acid  
in a solvent;  
performing repeated recrystallizations of the salt until a product  
of constant optical rotatory power is obtained;  
liberation of the salt by a base; and, if desired;  
formation of a salt with a pharmaceutically acceptable acid.  
!
!
[103] Apotex’ argument in this regard is articulated as follows:  
Claim 6 claims a general process, the Pasteur method referred to  
by many experts as the classic method, starting with the racemic  
mixture. Claim 7, then, narrows it where it is the levo-rotatory  
camphor-10-sulphonic acid that is used, a standard acid. Claim 8  
then narrows Claim 6 to use the solvent acetone. And Claim 9  
deals with comprising the formation of a salt in acetone. In sum,  
Apotex’ view is that claims should not just be read by themselves,  
Page: 34  
but in conjunction with the disclosure, because the claims on their  
own sometimes fail to tell enough.  
[104] In this case, the Court is not persuaded by Apotex’ argument.  
[105] Rather, a claim comparison and differentiation indicates that Claim 6 of the ‘777 Patent  
should be read, compared and contrasted with Claims 7 to 9. Indeed, Claims 7 to 9 also relate to the  
making of clopidogrel and its pharmaceutically acceptable salts. A reading of Claims 7 to 9  
confirms that they include specifications with respect to the solvent and optically active acid used.  
More particularly, Claim 7 relates to the process as described in Claim 6, but the optically active  
acid is specified as being levo-rotatory camphor-10-sulfonic acid. Claim 8 relates to the process as  
described in Claim 6, but specifies the solvent used in the recrystallization steps as acetone. Claim 9  
relates to the process as described in Claim 6, but specifies the solvent used in the formation of a  
salt as acetone.  
[106] Apotex nonetheless appears to allege that Claim 6 is limited to the acid and solvents  
discussed in Claims 7 to 9. The Court does not agree.  
[107] The Court recalls that the Supreme Court of Canada in Whirlpool, above, at para 49,  
emphasized that patent claims “must be read with a mind willing to understand”. Reading Claim 6,  
as proposed by Apotex, disturbs the flow and distorts the logic of the process claims (i.e. Claims 6  
to 9) and this runs counter to the Supreme Court of Canada’s interpretative guidance. Indeed, what  
would be the purpose and the relevance of the more specific Claims 7 to 9 if the more general  
process Claim 6 was limited in the manner suggested by Apotex? The Court also notes that, at page  
Page: 35  
2, the ‘777 Patent mentions that the levo-rotatory camphor-10-sulfonic acid is “advantageously  
used” and that acetone is “ideally suited”. This wording implies that other acids and solvents could  
be used as well. Hence, bearing in mind the guiding principles enunciated in Whirlpool, above, and,  
upon reading Claims 6 to 9, the Court finds that a person skilled in the art would construe Claim 6  
as not limiting the “optically active acid” to levo-rotatory (R)-camphor-10-sulfonic acid (Claim 7)  
and not limiting the solvent to a particular one. In sum, Claim 6 includes the use of optically active  
acids and solvents that result in the preparation of substantially pure clopidogrel and its  
pharmaceutically acceptable salts following the process described in Claim 6.  
G.  
What is the Meaning of “Medicine of the Invention” ?  
[108] The Court recalls that Apotex argues that the ‘777 Patent addresses matters of medicine,  
whereas Sanofi maintains that the ‘777 Patent refers to clopidogrel as a compound rather than a  
medicine.  
[109] Where there are technical terms in a patent, the Court is assisted by experts as to the  
meaning of such terms. The term the “medicine of the invention” as referred to in the ‘777 Patent is  
one such technical phrase that must be interpreted by the Court (Shire Biochem Inc., above, at para  
22; Whirlpool, above, at para 45). Indeed, the meaning of the phrase “medicine of the invention”  
informs the promise of the patent and must be ascertained at this stage of the analysis before the  
promise of the patent can be determined.  
[110] Central to this debate are also the meaning and use of the phrase “medicine of the invention”  
as well as “compound of the invention”.  
Page: 36  
[111] In order to address this issue, the Court must look to the wording of the ‘777 Patent and  
weigh the experts’ opinions.  
[112] First, the ‘777 Patent. The patent in referring to clopidogrel uses the terms “compound of the  
invention”, “derivative of the invention” and “medicine of the invention”.  
[113] At page 13, the ‘777 Patent, in the context of its discussion on salts, states the following:  
Among the mineral and organic acids salts of the dextro-rotatory  
isomer of the compound of Formula (Id) salts have been found which  
crystallize easily, are not hygroscopic and are sufficiently water-  
soluble as to make their use as active medicinal principles  
particularly advantageous.  
[Emphasis added]  
[114] Also, at page 20, the ‘777 Patent specifies that the medicine of the invention “can be made  
available for oral administration in the form of tablets, sugar-coated tablets ...”. The patent further  
specifies the unit doses for the compositions and the daily doses to be administered to patients to  
treat the disorders addressed by the patent.  
[115] Second, the experts. The experts opined on the significance of the meaning of the terms the  
“medicine of the invention”. For instance, in his report, at para 74, Dr. Davies stated that “[t]he  
invention of the ‘777 Patent improved PCR 4099 molecule by removing the enantiomer that  
contributed toxicity but no activity, thus providing a safer, more effective drug”. (Emphasis added)  
Page: 37  
[116] The exchange between counsel for Apotex and Dr. Shebuski is also instructive as to whether  
the “medicine of the invention” is clopidogrel as described in the ‘777 Patent (Shebuski, cross  
T5281-5294):  
Q. Dr. Shebuski, you will agree with me that clopidogrel is a medicine?  
A. Yes, sir.  
Q. Thank you. I want to ask you about the ‘777 Patent. Could you open it?  
A. I have it open, sir.  
Q. Perfect. You were anticipating my next move.  
A. I’m on page 21.  
Q. If you go to page 23 with me, I want to ask you about claims 10 and 11.  
You talk about those in your paragraphs 41 and 42. Claim 10 begins  
with the words “A pharmaceutical composition.” Am I correct that a  
skilled person reading this would understand that pharmaceutical refers  
to a drug or a medicine?  
A. Yes, sir. Properly formulated.  
Q. Properly formulated. And it’s a drug or medicine that’s intended to be  
given to people?  
A. It could be given to animals, as well, as a veterinary product.  
Q. Okay. You may have just anticipated this. The composition is the  
formulation or the thing that’s going to deliver the medicine to the  
patient?  
A. That’s correct. Composition could include the salt or the carrier or other  
excipients that were involved with the active ingredient, which we call  
the API or active pharmaceutical ingredient.  
Q. If we go forward, we’re told that the pharmaceutical composition  
comprises an effective amount of a compound according to claim 1. I  
want to ask you about the compound according to claim 1. That would  
be understood to be a reference to clopidogrel and its pharmaceutically  
acceptable salts, which are described in claim 1. Correct?  
A. Yes, sir.  
Q. When it says “an effective amount of clopidogrel and its pharmaceutically  
acceptable salts,” I take it the words “effective amount” reveal the concept  
of an amount that’s sufficient to treat whatever it is you're wanting to treat  
with the composition?  
A. Well, my analysis of it is slightly different. The effective amount is the  
amount that inhibits platelet aggression, which relates to the utility of this  
patent.  
Q. What amount of platelet aggregation? In the abstract? Any amount?  
A. Well, an effective amount. As I mentioned earlier in my testimony, we  
look at inhibition levels of 50 percent or greater as an effective amount.  
Q. Where is that said in the patent?  
A. It’s not said in the patent. That’s my own conjecture, sir.  
Page: 38  
Q. Conjecture. Okay. I’m going to suggest to you that, given that we are  
talking about a pharmaceutical composition, when it says, “Such a  
composition comprising an effective amount of clopidogrel and its  
pharmaceutically acceptable salts,” you have already told me clopidogrel  
is a medicine, so I’m going to suggest to you it’s an effective amount of  
the medicine to be able to do what the medicine is supposed to do. Do you  
agree with that?  
A. I have no basic disagreement with that.  
[Emphasis added]  
[117] Dr. Hirsh was also inclined to state that the “medicine of the invention” relates to  
clopidogrel and Dr. Levy was of the view that a compound, when active, can be a medicine even  
before it is formulated.  
[118] Thus, on the basis of the terms used in the ‘777 Patent, as well as the experts’ opinion on  
behalf of both Sanofi and Apotex, the Court agrees with Apotex and concludes that matters of  
medicine in the ‘777 Patent are “inescapable”. The Court accordingly finds that the “medicine of the  
invention”, as referred to in the ‘777 Patent, relates to clopidogrel.  
H.  
Page 21 of the ‘777 Patent  
[119] Another issue in dispute between the parties is the meaning of page 21 of the ‘777 Patent,  
which is an issue the Court needs to address as it will inform the promise of the Patent.  
[120] Page 21 of the ‘777 Patent contains one paragraph and it reads as follows:  
On account of its interesting inhibitory properties towards platelet  
aggregation and its interference in the mechanism of formation of  
arterial and venous thromboses, the medicine of the invention can be  
usefully administered in the treatment and prevention of platelet  
disorders due to extracorporeal blood circuits or the consequence of  
complications in atheroma.  
Page: 39  
[121] The positions of the parties regarding the above could not be further apart. Indeed, Apotex’  
position is that page 21 of the ‘777 Patent guarantees treatment in humans whereas Sanofi’s position  
is that page 21 of the ‘777 Patent does not in any way make reference to treatment in humans or, if it  
does, only to the “potential” for use in humans.  
[122] The expert evidence on this issue has not convinced the Court that the ‘777 Patent  
guarantees treatment of arterial and venous thrombosis as alleged by Apotex. The Court is equally  
unconvinced that the ‘777 Patent may refer to the “potential” for use in humans as alleged by  
Sanofi. A review of the testimony of the experts simply does not support either of the opposite  
views expressed by the parties at trial.  
[123] Whilst the ‘777 Patent does not refer to a guarantee, it does refer to more than a remote  
“potential” in humans. Unable to accept either of the two extreme interpretations of page 21 urged  
by the parties, the Court finds that the ‘777 Patent makes reference to use in humans.  
[124] The Court recalls that Dr. Hirsh, an expert for Apotex, in cross-examination, could not  
firmly conclude that page 21 of the ‘777 Patent promised treatment of venous thrombosis (Hirsh,  
T671-674):  
Q. And to the extent your report says that the patent promises treatment of  
venous thrombosis, that’s a bit of an inflation?  
A. Could I see where I said that?  
Q. Well, yes, sure. I mean if you don’t say it in your report, that’s fine. But  
let me find it.  
Well, for instance in paragraph 188 you are referring to ticlopidine and  
the racemate, but you do use the phrase prevention and treatment in  
Page: 40  
venous thrombosis. That’s paragraph 188, right at the bottom of the  
page, the top of the next page, page 64.  
A. Yes, but that’s a slightly different context isn’t it.  
Q. And that’s why, but when I read that I was saying, “well, why are you  
talking about treatment of venous thrombosis if the triple 7 doesn't  
promise that”?  
A. It’s just a statement of fact.  
Q. Fair enough.  
A. It’s a statement of fact, but I didn’t say it promised it. I was aware it was  
a mechanism. The only reason I would be interested in the mechanism  
would be if it had any utility, but that's implied rather than explicit.  
[Emphasis added]  
[125] However, Dr. Hirsh further testified that clopidogrel has a role in the mechanism of the  
formation of arterial and venous thrombosis (Hirsh, T682):  
Q. Let’s turn to the mechanism of formation of arterial and venous  
thrombosis which are the words that do appear.  
A. Yes.  
Q. I think you have already testified that platelets are involved in the  
formation of arterial and to a lesser degree venous thrombosis?  
A. Were they--yes, I have.  
Q. So if you have an inhibitor of platelet aggregation, its role in the  
mechanism of the formation of arterial and venous thrombosis is to  
prevent aggregation?  
A. Correct.  
Q. And that’s all it’s saying here?  
A. I see, um hmm.  
[Emphasis added]  
[126] Dr. Davies, on behalf of Sanofi, in his report at para 246, opined, with respect to page 21 of  
the ‘777 Patent, that it was not to be understood as a guarantee for use in humans:  
Consequently, when I read the entire paragraph on page 21, what is  
being said is that the improvement in activity and toxicity (based on  
animal testing) means that the medicine of the invention (i.e. if and  
when the compound is used as medicine) can (i.e. has potential) to be  
used for treatment. This is exactly what a skilled pharmaceutical  
chemist would take from the information in the patent. It would not  
be understood to be a promise of clinical approval, or a guarantee of  
use in humans.  
Page: 41  
[127] During the evidentiary phase of the trial, Dr. Davies elaborated on the above (T4425-4426):  
Q. In 246, you give your understanding of the last part of that paragraph  
on page 21. What is your understanding that you’re telling us there?  
A. What I’m saying there is, if you read the whole paragraph, the utility,  
from the first part of the paragraph, is the platelet aggregation  
inhibition. The rest of the paragraph suggests a potential use perhaps  
of that platelet inhibition.  
Q. Thank you. In paragraph 247, you refer to the claims and you make a  
comment that there's no use for treatment in humans. I think we’re all  
aware of that, but you refer then to claims 10 and 11?  
A. Yes.  
Q. What are you telling us in connection with claims 10 and 11?  
A. Claims 10 and 11 talk about pharmaceutical composition involving the  
clopidogrel as the constituent of that composition, but don't imply any  
use of that in humans. It could be in animals, for example.  
[Emphasis added]  
[128] In light of its earlier finding with respect to the meaning of the phrase “medicine of the  
invention”, the Court cannot accept such a restrictive reading down of the meaning of page 21 of the  
‘777 Patent, as suggested by Dr. Davies. The Court refers mutatis mutandis to the comments  
expressed by Justice Snider in Sanofi-Aventis Canada Inc. v Apotex Inc,, 2009 FC 676, 77 CPR (4th)  
99, (Ramipril), (decision affirmed on November 2, 2011 by the Federal Court of Appeal), at para  
128:  
[128] This passage demonstrates that Dr. Bartlett has not construed  
the claims in light of the promised utility; rather he has modified or  
read down the promise of the patent to suit his understanding of the  
claims. I cannot accept this reasoning. Such an approach to the  
question of the promise of the patent excuses the inventors from any  
requirement of precision in their claims or in the patent specification.  
If a patentee promises a particular result, he should be held to that  
promise. In expressing this view, I am not requiring commercial  
success or a certain level of commercial development to have taken  
place. …  
Page: 42  
[129] In the present circumstances, the language used at page 21 of the ‘777 Patent is not clear as  
to whether or not it guarantees that clopidogrel will “prevent” or “stop” the “mechanism of  
formation of arterial and venous thromboses”. There is simply no explicit wording to this effect.  
[130] Yet, the wording in the ‘777 Patent does not make it clear that the purpose is not for humans  
and the Court is not convinced that page 21 of the ‘777 Patent merely describes a “potential” use for  
humans.  
[131] In sum, the Court finds that Apotex is looking to inflate the meaning of page 21 of the ‘777  
Patent, whereas Sanofi is urging that it be read down. It is difficult if not impossible to conclude that  
page 21 of the ‘777 Patent clearly makes reference to a guaranteed treatment in humans. It is  
equally difficult to find that page 21 of the ‘777 Patent does not in any way make reference to  
treatment in humans. The Court is thus not prepared to conclude that page 21 of the ‘777 Patent is  
stripped of all reference to humans as advanced by Sanofi. How could this be when the diseases  
referred to at page 21 of the ‘777 Patent are not in animals but in humans (Hirsh, T391-393)? It  
necessarily means that it has a human purpose of some kind.  
[132] The Court accordingly concludes that the reference at page 21 of the ‘777 Patent that “the  
medicine of the invention can be usefully administered in the treatment and prevention of platelet  
disorders due to extracorporeal blood circuits or the consequence of complications in atheroma”  
confirms that clopidogrel on account of its properties, whilst not a guarantee, promises more than a  
mere potential: it can be used in the treatment of certain human thrombotic diseases.  
Page: 43  
I.  
The Invention described in the ‘777 Patent  
[133] The Court observes that there is no issue between the parties with respect to the inventive  
concept of the ‘777 Patent. The inventive concept was described as follows in the Supreme Court of  
Canada of the ‘777 Patent in the Plavix decision, at para 78:  
[78] In the present case, it is apparent that the inventive concept of  
the claims in the ‘777 patent is a compound useful in inhibiting  
platelet aggregation which has greater therapeutic effect and less  
toxicity than the other compounds of the ‘875 patent and the methods  
for obtaining that compound.  
[134] The ‘777 Patent is a selection patent (i.e. as stated in Plavix it is “one whose subject matter  
(compounds) is a fraction of a larger known class of compounds which was the subject matter of a  
prior patent”). Thus the Court must now address the question of how the inventive concept relates to  
the invention. More particularly, the question is the following: Do the salts and the advantages form  
part of the invention? Sanofi argues that the salts and the advantages could only relate to Claim 3  
and the bisulfate salt, whereas Apotex maintains that the salts and their advantages related to the  
invention described in the ‘777 Patent.  
[135] In Olanzapine, below, at para 78, the Federal Court of Appeal provided helpful guidance  
with respect to selection patents in the following:  
[78] With respect to selection patents, the inventiveness lies in the  
making of the selected compound, coupled with its advantage or  
advantages, over the genus patent. The selection patent must do  
more, in the sense of providing an advantage or avoiding a  
disadvantage, than the genus patent. The advantage or the nature of  
the characteristic possessed by the selection must be stated in the  
specification in clear terms…  
Page: 44  
[136] Thus, whilst in the context of a selection patent, the advantages will often necessarily form  
part of the invention, other scenarios remain possible. For example, the Court could hypothetically  
envisage a selection patent relating to the invention of a new process. In such a case, the new  
process could be found to be a second invention independent of the advantages stated in the  
selection patent. However, this is not the case with the ‘777 Patent because it relates to only one  
invention as discussed later in these reasons:  
!
Firstly, the process of splitting the racemate (PCR 4099) into  
two distinct enantiomers was not achieved through a new  
process. The process leading to the two enantiomers (the  
dextro-rotatory and the levo-rotatory) was performed following  
the Pasteur method.  
!
Secondly, a reading of the ‘777 Patent confirms that there is  
only one invention (pp 1 and 25) :  
At page 1 the patent states that “[t]he present invention  
relates to the dextro-rotatory enantiomer of methyl alpha-5  
(4,5,6,7-tetrahydro (3,2-c) thieno pyridyl) (2-chorophenyl)-  
acetate, a process for its preparation and pharmaceutical  
compositions containing it”.  
In an unexpected manner only the dextro-rotatory  
enantiomer I1 exhibits a platelet aggregation inhibiting  
activity, the levo-rotatory enantiomer I1 being active.  
Moreover, the inactive levo-rotatory enantiomer I1 is the less  
well tolerated of the two enantiomers.  
[Emphasis added]  
[137] Significantly, the ‘777 Patent at page 1 at line 29 refers to the invention mentioned and  
further specifies that: “the invention also relates to the addition of salts of the compound of formula  
(I1) with pharmaceutically acceptable mineral or organic acids”. Furthermore, the ‘777 Patent states  
at page 2 that the advantages provided by these salts include the characteristics of crystallizing  
easily, of not being hygroscopic and, being sufficiently water-soluble.  
Page: 45  
[138] The Court thus concludes from the wording of the ‘777 Patent that there is only one  
invention and the invention relates to salts of the compound and its advantages.  
[139] Therefore, the Court cannot agree with Sanofi’s contention that “there is one invention with  
different aspects, but each claim has to be considered separately within the invention”. The Court  
equally rejects the suggestion that the salts and the advantages may be peripheral to the invention.  
[140] In summary, the ‘777 Patent relates to one invention and that can be described as a  
compound which is useful in inhibiting platelet aggregation, has greater therapeutic effect and less  
toxicity than the other compounds of the ‘875 Patent, has the advantages of the salts (crystallize  
easily, not hygroscopic and sufficiently water-soluble) and the methods for obtaining that  
compound.  
J.  
Construction of the Promise of the Patent  
(1) General Principles  
[141] The promise of the patent is a question of law for the Court to decide, aided by the experts  
and considered through the eyes of the POSITA, as reiterated by the Federal Court of Appeal in Eli  
Lilly Canada Inc. v Novopharm Limited, 2010 FCA 197, 85 CPR (4th) 413, at para 80:  
[80] The promise of the patent must be ascertained. Like claims  
construction, the promise of the patent is a question of law. Generally,  
it is an exercise that requires the assistance of expert evidence:  
Bristol-Meyers Squibb Co. v. Apotex Inc., 2007 FCA 379, [2007]  
F.C.J. No. 1597 at para. 27. This is because the promise should be  
properly defined, within the context of the patent as a whole, through  
the eyes of the POSITA, in relation to the science and information  
available at the time of filing.  
Page: 46  
[142] Recently, Justice Hughes helpfully reviewed the concept of “the promise of the patent” in  
Pfizer Canada Inc. v Mylan Pharmaceuticals ULC, 2011 FC 547, 93 CPR (4th) 81, at paras 212-  
217. More specifically, Justice Hughes emphasized that “[i]n construing the specification of a  
patent, in particular the “promise”, the Court is to look at the specification through the eyes of a  
person skilled in the art, bearing in mind commercial realities, being neither benevolent nor harsh, in  
order to determine fairly the true intent”.  
[143] It is also worth recalling the role of the promise of the patent with respect to utility. On  
behalf of the Federal Court of Appeal, Justice Laydon-Stevenson in Ely Lilly Canada Inc., above,  
(FCA Olanzapine), at para 76, stated the following:  
[76] Where the specification does not promise a specific result, no  
particular level of utility is required; a “mere scintilla” of utility will  
suffice. However, where the specification sets out an explicit  
“promise”, utility will be measured against that promise:  
Consolboard; Pfizer Canada Inc. v. Canada (Minister of Health) ,  
[2009] 1 F.C.R. 253, 2008 FCA 108 (Ranbaxy). The question is  
whether the invention does what the patent promises it will do.  
[Emphasis added]  
[144] At this juncture, the Court recalls that, on the one hand, Apotex submits that the promise of  
the ‘777 Patent relates to humans and, on the other hand, Sanofi submits that it merely relates to  
‘potential use’ in humans.  
[145] For the reasons that follow, the Court finds that the ‘777 Patent makes an explicit promise  
for use of the compound in humans.  
Page: 47  
[146] The Court will first summarize the expert evidence with regard to the promise of the patent.  
(2) Summary of Expert Evidence  
Dr. Hirsh  
[147] Dr. Hirsh, on behalf of Apotex, opined that the ‘777 Patent is directed to the use of the  
dextro-rotatory enantiomer for use as a medicine for oral, rectal or parenteral administration for the  
purpose of treating and preventing platelet disorders due to extracorporeal blood circuits or the  
consequences of complications in atheroma. He also noted that the ‘777 Patent states that the  
dextro-rotatory enantiomer interferes with the mechanisms of arterial and venous thrombosis.  
[148] Dr. Hirsh further explained to the Court that the description of the compound in the ‘777  
Patent as being medicines and “active medicinal[s]” for therapeutic purposes would lead the  
haematologist/clinician to understand that this is a medicine for humans (rather than the laboratory  
rats used for the various tests reported in the ‘777 Patent). He also indicated that the diseases and  
conditions for which these compounds are promised to be useful in treating and preventing are  
clearly human diseases and conditions and that the dose administration section in the ‘777 Patent  
directs that the compound is for use in patients.  
Dr. Byrn  
[149] Dr. Byrn disagreed with Apotex’ experts including Dr. Hirsh’s interpretation of the promise  
of the ‘777 Patent. He stressed that pages 12 and 20 of the ‘777 Patent state that the results of these  
studies “demonstrate” that the “levo-rotatory isomer exhibits almost no platelet aggregation  
inhibiting activity and its toxicity is markedly higher than that of its dextro-rotatory homologue”. He  
Page: 48  
consequently concluded that the improvement in activity and toxicity (based on animal testing)  
means that the medicine of the invention (i.e. if and when the compound is used as medicine) can  
potentially be used for treatment. Dr. Byrn stated that a skilled pharmaceutical chemist would not  
understand the ‘777 Patent to be a promise of clinical approval, or a guarantee of use in humans.  
[150] Dr. Byrn thus rejected the interpretation that the ‘777 Patent made a promise of a specific  
result. He also rejected that there was such a promise of use in humans. He further explained that  
advantages of the dextro-rotatory enantiomer having all of the activity and being better tolerated are  
set out in the patent and are clearly based on the animal test data included. It was his opinion that  
any pharmaceutical chemist would interpret the ‘777 Patent as telling the world that very interesting  
results had been obtained and thus one might expect similar results would be achieved in humans,  
but no clear promise or guarantee that such results would be achieved in humans.  
Dr. Rodricks  
[151] In Dr. Rodricks’ opinion, a person skilled in the art would understand from general  
biological principles that the combination of platelet aggregation inhibiting activity and reduced  
toxicity documented in the ‘777 Patent for the dextro-rotatory enantiomer would suggest that the  
dextro-rotatory enantiomer holds promise as a useful human drug. Such a person would know,  
however, that the ‘777 Patent does not guarantee that the enantiomer would be a successful human  
drug. He or she would know that such a determination would require much more intensive  
investigation of the efficacy and safety of the material of the type required by Health Canada or the  
US Food and Drug Administration than could be expected in a patent. The available  
Page: 49  
pharmacological and toxicological data would indicate to a person skilled in the art that the dextro-  
rotatory enantiomer was a worthy candidate for further investigation and development as a drug.  
Dr. Shebuski  
[152] In Dr. Shebuski’s opinion, a person skilled in the art reading the ‘777 Patent would  
understand that it teaches that clopidogrel has platelet inhibiting activity and that this activity is not  
present in the other enantiomer. He further opined that the ‘777 Patent teaches that clopidogrel is  
better tolerated and less toxic than the other enantiomer and racemate. According to Dr. Shebuski,  
any person skilled in the art reading the ‘777 Patent would understand that these statements were  
based on animal testing. Given the knowledge at the time, he was of the view that a person skilled in  
the art would understand that these results indicate that clopidogrel’s platelet inhibiting activity  
could lead to an antithrombotic effect and that, since a person skilled in the art would understand  
that a compound with platelet inhibiting activity could be a potential antithrombotic agent, it would  
be understood that clopidogrel had potential to be used as an antithrombotic medicine. Furthermore,  
given that the basis for the statements in the ‘777 Patent are the pharmacology studies conducted in  
rats, Dr. Shebuski opined that a person skilled in the art would not understand the teachings of the  
‘777 Patent to be promising a specific result in humans. He therefore disagreed with Apotex’  
experts that the ‘777 Patent is explicitly promising that clopidogrel will be useful in humans in “the  
treatment and prevention of platelet disorders due to extracorporeal blood circuits or the  
consequence of complications in atheroma”.  
[153] In Dr. Shebuski’s opinion, Apotex’ experts’ focus on the human use of clopidogrel is  
inconsistent with how a person skilled in the art would understand the claims and the teachings of  
Page: 50  
the ‘777 Patent. He opined that a person skilled in the art would read the ‘777 Patent and note the  
following: (1) the first page of the ‘777 Patent focuses on the structure of clopidogrel and its  
advantages; (2) almost half of the disclosure (pages 2-11) relates to chemistry (i.e. process  
information and examples); (3) the pharmacological testing was conducted in rats; and (4) based on  
the information before it, page 21 sets out potential uses for clopidogrel.  
[154] Thus, Dr. Shebuski discarded Apotex’ experts’ reliance upon page 21 of the ‘777 Patent and  
their opinion that the ‘777 Patent made a promise that clopidogrel will have utility as a medicine in  
humans for the treatment and prevention of platelet disorders due to extracorporeal blood circuits or  
the consequence of complications in atheroma.  
[155] Additionally, Dr. Shebuski opined that the opening line at page 21 is “On account of its  
interesting inhibitory properties towards platelet aggregation and its interference in the mechanism  
of formation of arterial and venous thromboses….”. He stated that the basis for this statement is the  
interesting properties identified in the pharmacological study conducted in rats and that a person  
skilled in the art would understand that this one (1) paragraph contains an explanation of how  
clopidogrel could be put to therapeutic use. In particular, he opined that the inventors were stating  
that, in light of the interesting pharmacological properties observed in the rat studies, clopidogrel  
has the potential to be used in the treatment and prevention of platelet disorders due to  
extracorporeal blood circuits or the consequences of complications in atheroma.  
[156] Based on his reading of the ‘777 Patent and in particular the testing that is reported in the  
‘777 Patent, Dr. Shebuski concluded that if there were a promise of a specific result, it is that  
Page: 51  
clopidogrel has a platelet aggregation inhibiting activity and is better tolerated than the levo-rotatory  
enantiomer. According to Dr. Shebuski, a person skilled in the art would not have read the ‘777  
Patent as promising a specific result of clinical use in the treatment and prevention of platelet  
disorders due to extracorporeal blood circuits or the consequences of complications in atheroma.  
[157] Having summarized the expert evidence, the Court will now turn to consider the following  
question: What is the promise of the ‘777 Patent?  
(3) What is the Promise of the ‘777 Patent?  
[158] In this case, the question of the promise of the patent is whether the ‘777 Patent promises a  
result in humans, as argued by Apotex, or whether it merely promises potential use in humans, as  
argued by Sanofi. From the outset, the Court observes that neither the word “humans” nor the words  
“potential use in humans” are to be found in the ‘777 Patent.  
[159] In addressing the question of the promise of the patent, the Court will construe the promise  
in a purposive manner in accordance with the approach summarized by the Federal Court of Appeal  
in Olanzapine.  
[160] At this stage, it is also important to reiterate that determining the promise of a patent is a  
question of law (Bristol-Myers Squibb Co. v Apotex Inc., 2007 FCA 379, [2007] FCJ No 1597, at  
para 27).  
Page: 52  
[161] With the guiding principles of the FCA Olanzapine decision in mind and in order to  
determine the promise of the patent, the Court will now consider: (1) the wording in the ‘777 Patent;  
and (2) the relationship to the ‘875 genus Patent.  
(1) The Wording in the ‘777 Patent  
[162] When read as a whole and with a purposive approach, the wording used in the ‘777 Patent  
provides a number of indications that it promises in humans. In this regard, the Court finds the  
expert testimony of Dr. Hirsh, as summarized earlier, to be more persuasive than the expert  
tertimony of Dr. Byrn, Dr. Rodricks and Dr. Shebuski.  
[163] Indeed, the Court finds the wording used throughout the ‘777 Patent as making an explicit  
promise in humans, as argued by Apotex, as opposed to a mere indication of a potential purpose that  
the “medicine of the invention” could be put to use, as argued by Sanofi. The following wording in  
the ‘777 Patent is particularly revealing:  
!
“medicine” – The compounds are described as medicines and  
active medicinals for therapeutic purposes. The Patent indicates  
that clopidogrel has a better therapeutic index than the salt of the  
racemic mixture (p. 12). The Patent explains that clopidogrel is  
to be used for patients by oral, rectal or parenteral  
administration. Based on this wording, it would be reasonable  
for the POSITA to understand that clopidogrel is a medicine for  
humans rather than for rats.  
!
!
“patient” – The dose administration in the patent directs that the  
compound is for use in patients.  
“pharmaceutical compositions” – The ‘777 Patent informs that  
the compound is an oil but that the salts play an important role as  
they allow the transformation of the oil tablets. The ‘777 Patent  
further states that clopidogrel, as an oily product, is more  
difficult to purify and is difficult to use for the preparation of  
pharmaceutical compositions. In addition, it mentions a daily  
Page: 53  
dose range for the tablets varying from 0.0001 to 0.500 grams.  
Significantly, the ‘777 Patent indicates that the dosage will  
depend on the age of the patient and the severity of the disorder  
to be treated.  
!
“Active pharmaceutical index” – is referred to in the ‘777  
Patent which is intended for pharmaceutical use. Typically,  
active ingredients can be said to be given in the powder form but  
instead they are formulated into dosage forms i.e. tablets,  
capsules, and other dosage forms that are useful for  
administration.  
!
!
“medicine of invention” – As the Court concluded earlier,  
“medicine of the invention”, as referred to in the ‘777 Patent,  
relates to clopidogrel.  
“Page 21 of the Patent” – As the Court also concluded earlier,  
the Court’s finding in section H related to page 21 of the ‘777  
Patent that “the medicine of the invention can be usefully  
administered in the treatment and prevention of platelet disorders  
due to extracorporeal blood circuits or the consequence of  
complications in atheroma” confirms that clopidogrel on account  
of its properties can be used in the treatment of certain  
thrombotic human diseases.  
[164] All of the above illustrate that the ‘777 Patent promises in humans. However, in this case, a  
look at the context leading to the selection ‘777 Patent is also informative in reaching this  
conclusion. Thus, the Court turns to the relationship between the ‘875 genus Patent and the ‘777  
selection Patent.  
(2) The Relationship between the ‘875 Genus Patent and the ‘777 Selection Patent  
[165] In order to assess the promise of the ‘777 selection Patent, it is helpful to consider the ‘875  
genus Patent from which the compound in the ‘777 Patent was selected.  
Page: 54  
[166] Canadian Patent No. 1,194,875 (the ‘875 Patent) was filed in Canada on July 8, 1983 and  
issued on October 8, 1985. This patent relates to a large genus consisting of approximately 9.5  
million different compounds. The compounds disclosed in the ‘875 Patent are racemates. The  
general formula in the ‘875 Patent is as follows:  
O
Y
C
CH  
*
N
S
X
[167] Clopidogrel bisulfate is encompassed within the scope of the claims of the ‘875 Patent and  
was selected from this class of compounds.  
[168] The ‘875 Patent specifically mentions the applications of the compounds in human and  
veterinary therapeutics. Of significance is the following paragraph at page 12 of the ‘875 Patent:  
The toxicological and pharmaceutical investigations reported above  
demonstrate the low toxicity of the compounds of the invention, as  
well as their excellent tolerance and their inhibiting properties on  
blood-platelet aggregation, and their antithrombotic activity, which  
make them very useful in human and veterinary therapeutic  
applications.  
[Emphasis added]  
[169] Since the ‘875 Patent is the genus patent to the ‘777 Patent and that the ‘875 Patent  
explicitly refers to humans, the Court cannot accept Sanofi’s contention that the promise of the ‘777  
Patent is a mere potential in humans. Accepting Sanofi’s contention would mean accepting that the  
selection ‘777 Patent promises less than the ‘875 genus Patent. In this regard, the Court recalls the  
Page: 55  
conditions for a valid selection patent as defined in I.G. Farbenindustrie A.G.'s Patents, Re (1930),  
47 R.P.C. 289 (Eng. Ch. Div.), at pp 322-23:  
1. There must be a substantial advantage to be secured or  
disadvantage to be avoided by the use of the selected members.  
2. The whole of the selected members (subject to “a few exceptions  
here and there”) possess the advantage in question.  
3. The selection must be in respect of a quality of a special character  
peculiar to the selected group. If further research revealed a small  
number of unselected compounds possessing the same advantage,  
that would not invalidate the selection patent. However, if  
research showed that a larger number of unselected compounds  
possessed the same advantage, the quality of the compound  
claimed in the selection patent would not be of a special  
character.  
[170] Reading these conditions as a whole, it would be illogical to allow a selection patent to  
promise less than the genus patent – as the basic requirement for a selection patent is that it offers to  
the public a special advantage or character not disclosed by the genus. Although the Court would  
not go so far as to rule out that in some circumstances a selection patent could promise less than its  
genus patent, in the case at bar, the evidence leads the Court to find that this cannot be so.  
[171] In addition, although not determinative for the construction of a promise of a patent, the  
history of the development of the ‘777 Patent leads one to believe that the discovery of the invention  
of the ‘777 Patent was intended for human use. The selection ‘777 Patent does not promise less than  
its genus ‘875 Patent for the following reasons:  
!
!
!
the previous use of ticlopidine was in humans;  
the fact that ticlopidine is part of thienopyridine compounds;  
the work conducted by Sanofi to find a more potent drug than  
ticlopidine with a better risk/benefit ratio leading to the ‘875  
genus Patent;  
Page: 56  
!
!
the ‘875 genus Patent, like ticlopidine, is also part of the  
thienopyride compounds; and  
the ‘875 genus Patent explicitly refers to humans.  
(3) The Court’s Conclusion on the Promise of the Patent  
[172] As noted earlier, the Court is cognizant of the fact that the word “humans” is not explicitly  
found in the ‘777 Patent. However, a purposive interpretation of the ‘777 Patent has led the Court to  
find that the ‘777 selection Patent cannot promise less than the ‘875 genus Patent and this finding is,  
as explained earlier, supported by the wording in the ‘777 Patent.  
[173] In the circumstances, the Court accordingly concludes that the POSITA would understand  
that the promise in the ‘777 Patent is in humans. It follows that the Court cannot accept Sanofi’s  
position regarding the promise of the patent because to do so would totally ignore the work  
conducted prior to the ‘777 selection Patent and would amount to a reading down of the promise.  
This would also be inconsistent with the understanding of a person skilled in the art with respect to  
the well-known ticlopidine drug, the ‘875 Patent and the wording of the ‘777 Patent, including  
medicine, medicinal, patient, dosage, tablets, capsules, and pharmaceutical compositions.  
[174] In summary, the Court concludes that the POSITA would find the promise respecting the  
use of the invention of the ‘777 Patent to be a use in humans.  
[175] Notwithstanding the above, the Court must now consider a final argument advanced by  
Sanofi, referred to as the “matching principle” argument.  
(4) Sanofi’s “Matching Principle” Argument  
Page: 57  
[176] During final arguments, Sanofi raises before the Court the concept of the “matching  
principle” in connection with the promise of the patent.  
[177] More particularly, counsel for Sanofi refers to the Federal Court of Appeal’s recent decision  
in Eli Lilly (Olanzapine), above, which dealt with the ‘113 Patent, a selection patent for the  
compound olanzapine. In that case, Sanofi alleges that the Federal Court of Appeal reminded  
litigants and the lower courts that the construction of the utility of a patent must be consistent with  
the information in a patent and how a POSITA could interpret that information. Sanofi further  
submits that, in Eli Lilly (Olanzapine), the Federal Court of Appeal criticized Teva for taking the  
position that a particular animal model was not predictive of what would occur in humans, but at the  
same time also taking the position that a POSITA would read the patent as promising an effect in  
humans. In support of its argument, Sanofi refers to paras 102 and 103 in Eli Lilly (Olanzapine):  
[102] To illustrate, I refer to an example. In addressing the alleged  
advantages (to which I will return later), the trial judge noted that  
“Novopharm contested on numerous grounds the assertion in the ‘113 Patent  
about olanzapine’s advantage with respect to cholesterol” (para. 80). Among  
other things, Novopharm disputed the viability of using a dog model for  
predicting cholesterol effect in humans. The trial judge briefly reviewed the  
evidence of three experts in this respect. Only one, Dr. Bauer, felt the dog  
was a good model for predicting cholesterol effects in humans. However, his  
theory had been developed after the '113 Patent was filed. He agreed that the  
prevailing view in 1991 was that the dog was not a good model for  
cholesterol studies.  
[103] Therefore, the unanimous opinion (on the basis of the evidence  
referred to) was that the dog was not a good model for cholesterol studies.  
Notwithstanding, the trial judge concludes that “the reference in the ‘113  
Patent to the dog study and the cholesterol findings implies a concern about  
the potential effect in humans” (paras. 37, 38, 52, 93). Query, when the  
unanimous expert opinion was that the dog was not a good model for  
predicting cholesterol effects in humans, how could it be that a POSITA  
would read the reference to cholesterol levels in dogs as implying a concern  
about its potential effect in humans?  
[Emphasis added]  
Page: 58  
[178] The Court understands the “matching principle” argument advanced by Sanofi that states  
that the construction of the promise of a patent must be consistent with the information in a patent  
and how a POSITA would interpret that information. In this case, according to Sanofi, this would  
mean that there are no promises beyond the rats (rodents) because the data in the ‘777 Patent relates  
solely to rats. In support of its argument, Sanofi submits the following options for interpreting the  
promise of the ‘777 Patent:  
! Option 1: If POSITA would understand rat studies in patent to be  
predictive of activity in humans, then patent promises potential  
activity in humans.  
! Option 2: If POSITA would understand rat studies in patent not to be  
predictive of activity in humans, then patent does not promise any  
activity in humans.  
! Option 3 (Sanofi asserted that this was Apotex’ position): POSITA  
would understand rat studies in patent not to be predictive of activity  
in humans, but finds patent promises activity in humans.  
[179] In the Court’s opinion, the problem with Sanofi’s concept of the “matching principle” and  
its possible options would require the Court to look at the information in the ‘777 Patent from the  
prism of the rat studies data and, from that data, provide a construction of the patent that must be  
consistent with that information and how a POSITA would interpret that information.  
[180] However, the Court does not interpret the decision in Eli Lilly (Olanzapine), above, in the  
manner urged by Sanofi. Sanofi would like the Court to look at the rat studies data and construe the  
promise on the basis of that data. But this would lead to the illogical result that the promise of a  
particular patent could never be in humans if there is no human data in the patent itself. The Court’s  
understanding of the guidance stemming from the Federal Court of Appeal in Eli Lilly (Olanzapine)  
above, as enunciated by Justice Layden-Stevenson, is that a reading of the entire patent is necessary  
Page: 59  
to determine whether there is a promise and, only then, to consider whether the data supports the  
promise. The Court does not understand the teaching of the Federal Court of Appeal as reading first  
the data and assessing the promise of the ‘777 Patent in light of that data.  
[181] In light of the above, the Court cannot accept Sanofi’s “matching principle” argument in the  
circumstances.  
K.  
Summary on Claims Construction  
[182] After considering the words of the claims at issue of the ‘777 Patent and also considering the  
expert evidence, the Court concludes that the relevant claims of the patent should be construed as  
follows:  
! Claim 1 relates to substantially pure clopidogrel and its  
pharmaceutically acceptable salts.  
! Claim 3 relates to substantially pure clopidogrel bisulfate.  
! Claim 6 relates to the process for the preparation of the  
clopidogrel and its pharmaceutically acceptable salts including  
the use of “optically active acid” acid and solvents that result in  
the preparation of substantially pure clopidogrel and its  
pharmaceutically acceptable salts following the process  
described in claim 6.  
! Claim 10 relates to the pharmaceutical composition of  
substantially pure clopidogrel and its pharmaceutically  
acceptable salts in an effective amount as active ingredient.  
! Claim 11 relates to the pharmaceutical composition of  
substantially pure clopidogrel and its pharmaceutically  
acceptable salts in an effective amount as active ingredient.  
Page: 60  
[183] Having established the proper construction of the relevant claims of the ‘777 Patent, the  
Court now turns to the question of infringement.  
VI  
Infringement – Background  
A.  
Introduction  
[184] This proceeding consolidates two actions. The first (T-644-09) was the action by Apotex to  
impeach the ‘777 Patent and to declare Apotex’ proposed sale of clopidogrel tablets in Canada to be  
non-infringing of the claims of the ‘777 Patent. The second (T-933-09), which will now be  
determined by the Court, is Sanofi’s action for infringement of the ‘777 Patent. Sanofi argues that if  
the ‘777 Patent is valid, there is no debate that Apotex infringed product Claims 1, 3, 10 and 11 of  
the patent and the process claims – more particularly Claims 6 and 7. In response, Apotex asserts  
that its processes of manufacture do not infringe the product and the process claims of the ‘777  
Patent. Given the Court’s findings that the ‘777 Patent is invalid, which will be discussed in more  
detail later in the decision, the issue of infringement is in principle moot. Nonetheless, the Court will  
address the issue in order to respond to the views advanced by the parties in this regard, in the event  
this could potentially be of assistance.  
B.  
General Principles  
[185] Although the Patent Act does not provide a definition of “infringement”, s 44 of the Act  
(now s 42) outlines the exclusive rights granted to a patentee:  
GRANT OF PATENTS  
CONCESSION DES  
BREVETS  
What patent shall contain and  
Teneur et effet du brevet  
Page: 61  
confer  
44. Every patent granted under 44. Tout brevet accordé en  
this Act shall contain the title or vertu de la présente loi contient  
name of the invention, with a  
reference to the specification,  
and shall, subject to the  
conditions prescribed in this  
Act, grant to the patentee and  
le titre ou nom de l’invention,  
avec renvoi au mémoire  
descriptif, et accorde, sous  
réserve des conditions  
prescrites dans la présente loi,  
his legal representatives for the au breveté et à ses représentants  
term therein mentioned, from  
the granting of the patent, the  
exclusive right, privilege and  
légaux, pour la durée du brevet  
y mentionnée, à partir de la date  
de la concession du brevet, le  
liberty of making, constructing, droit, la faculté et le privilège  
using and vending to others to exclusifs de fabriquer,  
be used the invention, subject to construire, exploiter et vendre à  
adjudication in respect thereof  
before any court of competent  
jurisdiction.  
d’autres, pour qu’ils  
l’exploitent, l’objet de  
l’invention, sauf jugement en  
l’espèce par un tribunal  
compétent.  
GRANT OF PATENTS  
Contents of patent  
OCTROI DES BREVETS  
Contenu du brevet  
42. Every patent granted under  
42. Tout brevet accordé en  
this Act shall contain the title or vertu de la présente loi contient  
name of the invention, with a  
reference to the specification,  
and shall, subject to this Act,  
grant to the patentee and the  
le titre ou le nom de l’invention  
avec renvoi au mémoire  
descriptif et accorde, sous  
réserve des autres dispositions  
patentee’s legal representatives de la présente loi, au breveté et  
for the term of the patent, from à ses représentants légaux, pour  
the granting of the patent, the  
exclusive right, privilege and  
la durée du brevet à compter de  
la date où il a été accordé, le  
liberty of making, constructing droit, la faculté et le privilège  
and using the invention and  
selling it to others to be used,  
subject to adjudication in  
exclusif de fabriquer,  
construire, exploiter et vendre à  
d’autres, pour qu’ils  
respect thereof before any court l’exploitent, l’objet de  
of competent jurisdiction.  
l’invention, sauf jugement en  
l’espèce par un tribunal  
compétent.  
Page: 62  
[186] In Monsanto Canada Inc. v Schmeiser, 2004 SCC 34, 31 CPR (4th) 161, at para 35, the  
Supreme Court of Canada held that in order to determine if there was infringement, the question to  
be asked is the following: Did the defendant’s activity deprive the inventor, in whole or in part,  
directly or indirectly, of full enjoyment of the monopoly conferred by law? That monopoly is the  
exclusive right, privilege and liberty of making, constructing, using, vending and importing the  
invention to others to be used, subject to adjudication.  
[187] It is not disputed that the burden of proving infringement rests on the plaintiffs based on the  
balance of probabilities (see Eli Lilly and Co. v Apotex Inc., 2009 FC 991, 80 CPR (4th) 1,  
[Cefaclor], at para 211; Weatherford Canada Ltd. v Corlac Inc., 2010 FC 602, 84 CPR (4th) 237, at  
para 170; Lubrizol Corp. v Imperial Oil Ltd. (FCA), [1992] FCJ No 1110, 45 CPR (3rd) 449).  
[188] Furthermore, the question of infringement is a mixed question of fact and law, as explained  
in Hughes and Woodley, Patents, 2nd ed (Markham, ON: LexisNexis, 2005) at 375:  
[…] The question of infringement is a mixed question of fact and  
law. The construction and scope of the patent is a matter of law;  
whether the defendant’s activities fall within the scope of the patent  
is a question of fact, the burden being on the patentee to prove  
infringement. […]  
[189] The guiding principles regarding the concept of “use” under s 42 of the Patent Act were  
outlined in a comprehensive manner in Monsanto, above, at para 58, as follows:  
[58] …  
1. “Use” or “exploiter”, in their ordinary dictionary meaning,  
denote utilization with a view to production or advantage.  
Page: 63  
2. The basic principle in determining whether the defendant has  
“used” a patented invention [page 927] is whether the inventor  
has been deprived, in whole or in part, directly or indirectly, of  
the full enjoyment of the monopoly conferred by the patent.  
3. If there is a commercial benefit to be derived from the invention,  
it belongs to the patent holder.  
4. It is no bar to a finding of infringement that the patented object or  
process is a part of or composes a broader unpatented structure  
or process, provided the patented invention is significant or  
important to the defendant’s activities that involve the  
unpatented structure.  
5. Possession of a patented object or an object incorporating a  
patented feature may constitute “use” of the object’s stand-by or  
insurance utility and thus constitute infringement.  
6. Possession, at least in commercial circumstances, raises a  
rebuttable presumption of “use”.  
7.  
While intention is generally irrelevant to determining whether  
there has been “use” and hence infringement, the absence of  
intention to employ or gain any advantage from the invention  
may be relevant to rebutting the presumption of use raised by  
possession.  
[190] It is further recalled that intention is not material to a finding of infringement. However,  
intention plays an important role in determining the nature of the remedy. Punitive damages may be  
affected by whether or not there was knowledge or intent (Monsanto, above, at para 86).  
[191] Justice Gauthier of the Federal Court, as she then was, in Cefaclor provided a full and  
comprehensive analysis on this issue of importation and infringement. At para 318, Justice Gauthier  
reiterated that the monopoly granted to a patentee extends so as to preclude the importation into  
Canada of products made abroad in accordance with processes that would, if practiced in Canada,  
constitute an infringement of the patent:  
Page: 64  
[318] … Importation of products made abroad that are the subject of  
patented process claims in Canada is prohibited. This prohibition is  
widely recognized and is well-settled law in Canada.  
[192] It has also been held that the export from Canada of a patented product to be used abroad is  
considered to be an act of infringement (AlliedSignal Inc. v Du Pont Canada Inc. et al. (1995), 61  
CPR (3d) 417 (FCA).  
[193] When addressing a question of infringement, the Court must first construe the claims. Once  
the construction and scope of the claims have been determined, the Court must then determine if the  
patentee has successfully proven that said claims have been infringed.  
C.  
Summary of Sanofi’s Case on Infringement  
[194] Sanofi argues that Apotex’ activities constitute acts of infringement. According to Sanofi,  
Apotex infringed the ‘777 Patent because Apotex imported, offered for sale, sold, made, possessed  
for commercial purposes, used and exported clopidogrel bisulfate and clopidogrel bisulfate tablets.  
Sanofi asserts that these acts constitute use of the invention of the ‘777 Patent which deprives  
Sanofi, the patentee, and BMS, its exclusive licensee, of the full enjoyment of the monopoly granted  
and the right to exclude others from practicing the invention of the ‘777 Patent. More particularly,  
the alleged infringement results from the following activities:  
!
!
!
!
[omitted];  
[omitted];  
[omitted]; and  
[omitted].  
Page: 65  
[195] In response, Apotex has argued that the process employed by its supplier located in […] […]  
falls outside of Claim 6. Sanofi, on the other hand, maintains that it is clear that the process used is  
within Claim 6 and that Apotex is importing the product of this process. Sanofi further asserts that  
the alleged differences are minor variations from the process literally described in the disclosure of  
the patent and that the process thus still falls within the wording of Claim 6. Sanofi also argues that  
the defences advanced by Apotex, i.e. the limitation period defence and the defence based on the  
Settlement Agreements, estoppel and abuse of process, are unfounded in both fact and law.  
[196] Consequently, Sanofi submits it is entitled to all damages arising from Apotex’ infringing  
acts or disgorgement of the profits unjustly gained by Apotex, as Sanofi may elect. In addition,  
Sanofi seeks an injunction and the delivery up of all bulk clopidogrel and tableted clopidogrel  
within the possession, power or control of Apotex and Pharmachem.  
[197] Given the Court’s finding with respect to utility and obviousness, there is no need at this  
stage to decide on a possible injunction or the award of damages and interest. Therefore, the Court’s  
analysis will focus essentially on infringement, and in light of the foregoing, the Court will now  
determine if the patentee, Sanofi, has met its burden of demonstrating that Apotex infringed the  
claims of the ‘777 Patent.  
D.  
The Evidence before the Court  
[198] The Court recalls that during trial, Dr. Bernard Sherman, the Chair of Apotex, testified that  
the decision had been made to develop a clopidogrel bisulfate product because it was going to be  
commercially successful. [omitted] .  
Page: 66  
[199] [omitted] .  
[200] [omitted] .  
[201] [omitted] .  
[202] According to the evidence, Apotex began acquiring significant quantities of clopidogrel  
bisulfate from […] in early 2004 and continues to receive material to this day. Apotex has received  
over 80,000 kilograms of clopidogrel, which represents a value to Apotex of about 1.6 billion USD  
on the U.S. market at Apotex’ selling price.  
[203] It was also submitted in evidence that the bulk clopidogrel received by Apotex from […]  
was delivered by an agent of […] to Air Canada and delivered to Canada pursuant to an Air Waybill  
issued out of Montreal. Notwithstanding the fact that from February 13, 2006, the shipments were  
indicated to be on a CIF basis and that prior to that date they are indicated to be on a DDU  
(delivered duty unpaid) basis, it can be seen on the Air Waybills and the Canada Customs Coding  
Forms that Apotex is the “importer” for the purposes of Canada customs declarations. Thus, the  
Court finds, as argued by Sanofi, that Apotex’ importation of clopidogrel bisulfate constitutes an act  
of infringement (see Schmeiser, above, at para 44; Cefaclor, above, at paras 270-329).  
Page: 67  
[204] Once the goods clear customs, the bulk clopidogrel imported by Apotex is then trucked to  
Apotex’ manufacturing plant where it is formulated into tablets containing 75 mg of clopidogrel  
bisulfate and henceforth ready for sale.  
[205] In addition to having sold large quantities of clopidogrel bisulfate 75 mg tablets in a variety  
of countries, Apotex sold approximately 500 million tablets to the U.S. market between August 8,  
2006 and August 31, 2006 until it was enjoined to cease these sales by the U.S. District Court  
Southern District of New York on October 23, 2009, in view of the U.S. Patent. During trial, Sanofi  
brought to the attention of the Court that after this injunction was issued, it is not clear what became  
of the unsold material, i.e. whether it was returned to Canada, shipped to other countries or retained  
in the U.S. During cross-examination, [omitted]:  
Q. [omitted]?  
A. [omitted].  
Q. [omitted]?  
A. [omitted].  
Q. [omitted]?  
A. [omitted].  
Q. [omitted]?  
A. [omitted].  
Q. [omitted]?  
A. [omitted].  
Q. [omitted]?  
A. [omitted].  
[206] At an average selling price of $2.00 per tablet, the value to Apotex of the sale of the missing  
tablets would represent approximately 1 billion USD. The lack of evidence regarding these missing  
tablets is certainly perplexing.  
Page: 68  
[207] The evidence further demonstrates that Apotex sold clopidogrel bisulfate to numerous other  
countries. As of January 15, 2011, Apotex had received and filled purchase orders in Canada for  
over 77 million tablets transported to Hong Kong, New Zealand, Iran, Libya, Malaysia, Singapore,  
Oman, Haiti, Moldova, Thailand, Hungary, the Philippines, Ukraine, Sierra, Australia, etc. Sanofi  
submits that the acceptance of purchase orders and manufacture in Canada and sale for export are  
further infringing acts committed by Apotex (see AlliedSignal Inc., above, at paras 72-73). The  
Court, based on the evidence, agrees and so finds.  
[208] Sanofi also submits that the possession of a patented good for a commercial purpose is an  
act of infringement (see Schmeiser, above, at paras 46-58). In support of this claim, Sanofi  
explained to the Court that with respect to the U.S. sales by Apotex to Apotex Corp., the purchase  
orders were received and processed in Canada. Although the commercial invoices for the U.S. sales  
do not indicate any commercial terms, Apotex appropriates the goods in fulfillment of these  
purchase orders and accordingly the transfer of title occurs in Canada. Hence, the Court again  
agrees with Sanofi that, based on the evidence, Apotex committed an act of infringement by  
possessing the patented good at issue for commercial purposes.  
[209] In the customs documentation, Apotex is represented by Apotex’ U.S. customs agent,  
Affiliated Customs Brokers of Detroit, Michigan, as the importer of record. After the goods are  
cleared through U.S. customs by the agent of Apotex, they are shipped to the warehouse of Apotex  
Corp., Apotex’ U.S. marketing entity. The sales by Apotex Corp. are made pursuant to an  
Abbreviated New Drug Application (ANDA) in the name of Apotex and regulatory approval  
obtained by Apotex Inc. with Apotex Corp. acting as its agent.  
Page: 69  
[210] Based on all of these findings of infringing acts, it is clear that Apotex acted in a manner that  
interferes with the full enjoyment of the monopoly that had been granted to Sanofi. The Court  
concludes that Apotex committed acts of infringement by manufacturing, using, importing,  
exporting, possessing and selling a product protected by the ‘777 Patent without the permission of  
Sanofi. The Court will now examine how the infringing acts relate to the product claims and the  
process claims.  
(1) Product Claims: Claims 1, 3, 10 and 11  
[211] The Court recalls Apotex’ pleadings with respect to the issue of the enantiomeric purity of  
the clopidogrel referred to in Claims 1, 3 10 and 11. As concluded earlier, experts on both sides  
have agreed that the purity of the clopidogrel claimed in the ‘777 Patent is substantial purity. Hence,  
there is no issue with respect to the construction of Claims 1 and 3 of the ‘777 Patent, which relates  
to substantially pure clopidogrel bisulfate.  
[212] With respect to Claims 10 and 11, there is no dispute that they relate to pharmaceutical  
compositions containing clopidogrel or its pharmaceutically acceptable salts.  
[213] In light of the evidence that was before the Court, there is no question that the acts  
committed by Apotex infringe Claims 1, 3, 10 and 11 of the ‘777 Patent. The Court agrees with  
Sanofi that the product claims were infringed by virtue of Apotex having made, used, possessed and  
sold clopidogrel bisulfate and pharmaceutical compositions (75mg tablets) containing clopidogrel  
bisulfate for others to be used.  
Page: 70  
(2) Process Claims: Claims 6 to 9  
[214] First and foremost, Sanofi claims that Apotex’ supplier, […], used a process to produce bulk  
clopidogrel which infringes Claim 6 of the ‘777 Patent, and that Apotex furthermore imported the  
product of that process.  
[215] In this regard, Sanofi relies on subsection 39(2) of the Patent Act and contends that where a  
patent claims a process to make a new product, “any substance of the same chemical composition  
and constitution shall, in the absence of proof to the contrary, be deemed to have been produced by  
the patented process” (subsection 39(2) of the Patent Act).  
[216] Subsection 39(2) of the Act therefore imposes the burden of proof on Apotex to demonstrate  
that its supplier’s process does not infringe any of the process claims. The Court observes that  
Sanofi’s infringement argument on process claims principally concerns Claims 6 and 7.  
[217] In Free World Trust v Électro Santé Inc., 2000 SCC 66, 9 CPR (4th) 168, at paras 55-57, the  
Supreme Court of Canada held the following with regards to process infringement:  
[55] It would be unfair to allow a patent monopoly to be breached  
with impunity by a copycat device that simply switched bells and  
whistles, to escape the literal claims of the patent. Thus the  
elements of the invention are identified as either essential elements  
(where substitution of another element or omission takes the  
device outside the monopoly), or non-essential elements (where  
substitution or omission is not necessarily fatal to an allegation of  
infringement). For an element to be considered non-essential and  
thus substitutable, it must be shown either (i) that on a purposive  
construction of the words of the claim it was clearly not intended  
to be essential, or (ii) that at the date of publication of the patent,  
the skilled addressees would have appreciated that a particular  
Page: 71  
element could be substituted without affecting the working of the  
invention, i.e., had the skilled worker at that time been told of both  
the element specified in the claim and the variant and “asked  
whether the variant would obviously work in the same way”, the  
answer would be yes: Improver Corp. v. Remington, supra, at p.  
192. In this context, I think “work in the same way” should be  
taken for our purposes as meaning that the variant (or component)  
would perform substantially the same function in substantially the  
same way to obtain substantially the same result. In Improver  
Corp. v. Remington, Hoffmann J. attempted to reduce the essence  
of the Catnic analysis to a series of concise questions, at p. 182:  
(i) Does the variant have a material effect upon the  
way the invention works? If yes, the variant is  
outside the claim. If no: --  
(ii) Would this (i.e.: that the variant had no material  
effect) have been obvious at the date of publication  
of the patent to a reader skilled in the art? If no, the  
variant is outside the claim. If yes: --  
(iii) Would the reader skilled in the art nevertheless  
have understood from the language of the claim  
that the patentee intended that strict compliance  
with the primary meaning was an essential  
requirement of the invention? If yes, the variant is  
outside the claim.  
[56] The three questions are not exhaustive but they encapsulate  
the heart of Lord Diplock’s analysis, and have been endorsed in  
subsequent English cases.  
[57] In AT & T Technologies, supra, at p. 257, Reed J. derived a  
series of interpretive principles from Catnic, supra, O'Hara, supra,  
and other cases. Her third principle is as follows:  
(3) if a variant of an aspect of a claim has no material  
effect on the way the invention works there is a  
presumption that the patent is infringed and that the  
patentee intended that that variant falls within the  
scope of the claim... [Emphasis in original]  
[Emphasis added]  
Page: 72  
[218] In sum, if modifications are brought into a claimed process but the essential elements  
remain, there is still infringement.  
[219] Apotex maintains that the bulk clopidogrel bisulfate used in its Apo-clopidogrel tablets is  
manufactured by the process outlined in […] U.S. and Canadian Drug Master File. Sanofi submits  
that the steps in this process that are relevant to the infringement of Claim 6 are described in  
[omitted].  
[220] Turning to Claim 6, as previously explained in the section on the construction of claims, this  
claim identifies a three (3) step process for the preparation of clopidogrel.  
[221] Apotex’ position is that Claim 6 should be read as limited to acetone as the solvent and to  
(R)-camphorulfonic acid as the optically active acid. Sanofi argues that this is too narrow a  
construction.  
[222] The two relevant expert witnesses who testified on this issue were Dr. Adger, for Apotex  
and Dr. Byrn, for Sanofi. Dr. Adger opined that neither of the processes he was provided with by  
Apotex have the essential elements of Claim 6. Dr. Adger appeared to suggest that because the  
[omitted], it does not fall within the scope of any of the process claims of the ‘777 Patent.  
[223] On the other hand, Dr. Byrn in his Expert Report, at para 173, concluded as follows:  
Thus in my opinion, the process described in these documents  
not only uses the teachings of the ‘777 Patent, but is within  
Page: 73  
claim 6. The process described is a simple variation of what is  
specifically set out in the examples. [omitted]. The process  
though is within the words of claim 6. The product of the  
process is within claims 1 and 3.  
[224] In support of his opinion, Dr. Byrn submitted a table to help the Court visualize the slight  
variation between Claim 6 and the […]. It is clear to the Court that the only difference is that the  
[omitted] :  
Claim 6 Process  
[omitted]  
Formation of a salt of the racemate with an  
optically active acid in a solvent,  
[omitted]  
[omitted]  
[omitted]  
Repeated recrystallization of the salt, are  
carried out until a product of constant  
optical rotatory power is obtained,  
Liberate clopidogrel from its optically  
active salt using a base  
[omitted]  
[omitted]  
If  
desired,  
add  
pharmaceutically  
acceptable acid to make clopidogrel salt  
[225] In order to visually depict the two processes, Dr. Byrn submitted the following drawings:  
Page: 74  
Page: 75  
Apotex’ Documents  
[omitted]  
[226] In cross-examination, Dr. Adger, the expert for Apotex, agreed there was only a slight  
variation between Claim 6 and the […]. In fact, when asked to compare the two diagrams above, he  
characterized them as being “black and white” and agreed that they were almost mirror images of  
each other (Adger, cross T1781-1782):  
Q. The process described taking the right hand side of the diagram  
on page 5 and switching it to the left?  
A. It’s like black and white.  
Q. Or the reverse?  
A. Right.  
Q. It’s like mirror images?  
A. Almost.  
Q. If you look at claim 6 and keep your tab 8, or the more detailed  
description that wasn’t provided to you in front of you, you’d  
agree, following the resolution in tab 8, Clopidogrel is made?  
A. Yes.  
Q. [omitted]?  
A. [omitted].  
Q. [omitted]?  
A. [omitted].  
Q. [omitted]?  
A. [omitted].  
[227] Although Dr. Adger nuanced his answer in re-examination, Sanofi contends that Dr.  
Adger’s only argument with respect to infringement is limited to the following aspect of Claim 6:  
the salt that is recrystallized to form the clopidogrel salt must be the same as the precipitate that  
forms initially from the addition of the optically acid salt to the racemic mixture.  
Page: 76  
[228] Dr. Byrn’s testimony was useful in explaining that when the optically active salt is added to  
the racemic mixture, in both the Claim 6 process and the […], two optically active salts are formed,  
one of which stays in the solution (Byrn Report, para 171):  
[171] Dr. Adger’s statement in paragraph 266 that “the salt did not  
arise from the racemic mixture but rather from an enantiomerically  
enriched sample” is simply pedagogical nonsense. The salt is the salt  
in solution and any synthetic or solid state chemist who understands  
salt formation would understand that claim 6 covers any separation  
regardless of whether the desired salt precipitates or remains in  
solution. The act of the precipitation enantiomerically enriches both  
the broth and the precipitated salt.  
[229] In light of this evidence, the Court finds the testimony of Dr. Byrn to be more persuasive  
than the testimony of Dr. Adger. As clearly explained by Dr. Byrn, the only difference between the  
two processes is that an additional step is included in the [omitted]. This amounts to a mere  
tweaking of the process. Consequently, the Court considers that Apotex has infringed Claim 6 of the  
‘777 Patent.  
[230] As for Claim 7, which relates to the process described in Claim 6, it specifies levo-CSA as  
the optically active solid. [omitted]. Therefore, Apotex argues that the […] does not fall within the  
scope of Claim 7. As Sanofi pointed out, [omitted] and the Court accepts this argument.  
[231] Finally, with regards to Claims 8 and 9, Apotex submits that the […] does not employ  
acetone. As already indicated in the discussion in connection with Claim 6, the Court does not  
accept that these claims should be read as limiting acetone as the solvent. Thus, in light of the  
evidence, the Court concludes that Apotex infringed the process Claims 6 to 9 of the ‘777 Patent.  
Page: 77  
E.  
Potential Exemption from Liability  
[232] The common law has long recognized an exemption from liability for infringement known  
as the experimental use exemption. More particularly, an experimental user, without a licence, in  
the course of a bona fide experiment with a patented article is not, in law, an infringer. This  
exception, set out in s 55.2(1) of the Patent Act (post-October 1, 1989), provides that it is not an  
infringement to use the invention solely for uses reasonably related to the development and  
submission of information required by law:  
Exception  
Exception  
55.2 (1) It is not an  
55.2 (1) Il n’y a pas contrefaçon  
infringement of a patent for any de brevet lorsque l’utilisation, la  
person to make, construct, use  
or sell the patented invention  
solely for uses reasonably  
related to the development and  
submission of information  
required under any law of  
fabrication, la construction ou  
la vente d’une invention  
brevetée se justifie dans la seule  
mesure nécessaire à la  
préparation et à la production  
du dossier d’information  
Canada, a province or a country qu’oblige à fournir une loi  
other than Canada that regulates fédérale, provinciale ou  
the manufacture, construction,  
use or sale of any product.  
étrangère réglementant la  
fabrication, la construction,  
l’utilisation ou la vente d’un  
produit.  
(1) Apotex’ Alleged Experimental Use  
[233] Canadian courts have consistently held that the use of a patented invention for the purpose  
of submission to regulatory authorities was exempt from infringement (see Smith Kline & French  
Inter-American Corp. v Micro Chemicals Ltd., [1972] SCR 506; Merck & Co. Inc. v Apotex Inc.,  
2006 FC 524, [2006] FCJ No 671, at paras 157-161, rev’d on other grounds, 2006 FCA 323, [2006]  
FCJ No 1490). Apotex relies on this exception to argue that it should not be held liable for any  
infringement relating to its experimental and regulatory uses of clopidogrel.  
Page: 78  
[234] In support of its position, Apotex relies on the testimony of Mr. Fahner who reviewed the  
documents relating to Apotex’ use of clopidogrel for regulatory purpose. Mr. Fahner prepared  
charts which identified the amount of raw material from each lot it received that Apotex used for the  
various research and development activities involved in the formulation development process, and  
charts which identified the amounts of clopidogrel from each lot Apotex received that were sampled  
and retained for ongoing regulatory purposes, or consumed in complying with the regulatory  
requirements for in-process quality controls.  
[235] Notwithstanding the fact that Sanofi did not challenge the application of the exception,  
Sanofi did object in respect of certain specific lots on the basis that no documents were provided  
that would show that the material was used solely for regulatory purposes.  
[236] In the present case, the evidence shows that there has been a use of clopidogrel that should  
be considered in the circumstance of "fair dealing". However, the Court is not convinced that  
Apotex met its burden of proving that such an exception applies. Apotex failed to provide the Court  
with evidence relating to what was ultimately done with the bulk material or tablets. Accordingly,  
[omitted] :  
Q. [omitted]?  
A. [omitted].  
Q. [omitted]?  
A. [omitted].  
Q. [omitted]?  
A. [omitted].  
Page: 79  
[237] Mr. Barber also testified about which records would be available within Apotex’ SAP  
system (Apotex’ inventory system) (Barber, cross T1064-1065). The evidence demonstrates that  
Apotex does not keep a record of inventory of tablets made for regulatory purposes:  
Q. And the SAP system we are looking at here, it’s supposed to  
collect all information for inventory purposes; that’s one of its  
purposes?  
A. I guess it depends what you mean by “all information”, I am  
not sure.  
Q. Well, it would record receipt of bulk material?  
A. Yes, it would.  
Q. It would record transfer of bulk material to the formulation  
department?  
A. Yes, it would.  
Q. It would record how many tablets had been created from that  
material?  
A. It would if it’s a commercial product. Formulation development  
tablets are not in the SAP system.  
Q. Okay.  
A. So the raw material aspect of what formulation development  
does is captured there, but anything we turn into trials is not in  
SAP.  
Q. Let’'s deal with the commercial side.  
A. Okay.  
Q. It would also include sales of the tablets?  
A. I believe it would, yes.  
Q. And would it also include material that might have to be  
destroyed for any purpose; stale-dated product, let’s say?  
A. It would reconcile it somehow. I don’t know if it would show it  
was destroyed. There would be a record, a paper record of the  
destruction and some way of reconciling that amount in SAP.  
Q. Okay. And are you aware that Apotex on occasion, has  
transferred regulatory material into commercial material?  
A. No, I am not aware that’s ever happened.  
Q. You are not aware of that ever occurring?  
A. I am not aware that’s ever happened.  
Q. Okay. If that did happen, the SAP system would record that?  
A. I don’t think we have any other way of selling it if it’s not  
within the system, so I think it would have to be.  
Q. Do you keep inventory of bulk that’s left on hand?  
A. Bulk of what?  
Q. Bulk clopidogrel bisulphate.  
A. Of formulation development trials, or...  
Page: 80  
Q. Does the SAP system, if you punched in whatever numbers,  
could you get the amount of bulk sitting in the warehouse  
today?  
A. Of raw material, yes.  
Q. Okay, could you also plug in and figure out how many tablets  
were sitting in the warehouse today?  
A. Commercial tablets, yes.  
Q. Yes. What about regulatory?  
A. No.  
Q. So you don’t keep a record of inventory of, let’s say, hundreds  
of thousands of tablets that was made for regulatory purposes?  
A. No, the regulatory aspect doesn’t require anything to happen in  
SAP. Again, formulation development makes our batches  
outside of SAP system. At the time when a product is being  
developed, SAP is not structured necessarily to receive all that  
information, and we go through so many iterations of  
formulations and that would all require a separate development  
of codes and stuff to manage that, and it's just not practical for  
us to do that.  
Q. Are records kept as to what happens to regulatory material?  
A. We would have records, yes.  
Q. And those records would include how it was utilized, and you  
have included some of those here?  
A. Yes. And executed batch records would be one of the records  
we’d have in terms of how much we produced.  
Q. And would you have an inventory record of what happened to  
that material after it was utilized?  
A. We don’t have inventory records per se, but we do keep the  
inventory and, we would have it on file there and we could  
verify the amount that's present at any given point in time. Also  
if we destroy it, there would be a destruction record that shows  
how much we destroyed.  
Q. Okay, so there should be destruction records if things were  
destroyed?  
A. Yes.  
[238] In light of the absence of records regarding inventory of regulatory material and given  
Apotex’ failure to tender evidence as to the alleged destruction records of the disputed lots, the  
Court cannot rule out the possibility that all or some of the raw material or the actual formulations  
that were made in the course of that development process were ever sold or used for commercial  
purposes. Thus, the Court concludes that Apotex failed to demonstrate that the exception of  
Page: 81  
experimental use found in s 55.2(1) of the Act with respect to the disputed lots applies.  
Consequently, Apotex must be found liable for the infringement of the regulatory material it  
developed.  
F.  
Apotex’ Defences to Infringement  
[239] In this proceeding, Apotex raises the following defences as to non-infringement on the  
following basis: (i) limitation period, and (ii) estoppel and abuse of process. As such, it is important  
to note that Apotex bears the burden of proof as to each of these defences.  
(1) The Limitation Period  
[240] Apotex asserts that Sanofi is statute-barred from seeking any relief in respect of activities  
taking place more than two years from the commencement of the action in T-933-09, namely before  
June 9, 2007. Apotex relies on section 39(1) of the Federal Courts Act, RSC 1985, c F-7, which  
provides default limitation provisions in the event that there is no express limitation provision  
provided in any other federal statute. This provision, as discussed in more detail later, directs that  
where the cause of action arises in a province, one applies the laws of prescription and limitation in  
force in that province.  
[241] Thus, because Apotex asserts that the cause of action arose entirely in the province of  
Ontario, it relies on section 4 of the Limitations Act (Ontario), RSO 1990, c L-15, which provides a  
two-year limitation period.  
Page: 82  
[242] Apotex further argues that while the current Patent Act contains an explicit limitation  
provision at section 55.01, it cannot be applied in the present case because the transitional  
provisions relating to this section could arguably be read as excluding from its application actions  
for infringement of patents issued under the “Old Act”.  
[243] Pursuant to the transitional provision in section 78.2 of the Act, “any matter” in relation to  
its validity or infringement falls to be determined under the provisions of the Act as it read  
immediately before October 1, 1989. Thus, Apotex maintains that such provision is not applicable  
to the present case because none of those provisions contained a limitation period.  
[244] On this basis, Apotex asserts that the provincial limitation period of two years applies so as  
to bar any claims being asserted in connection with the manufacture and sale of the Apotex  
clopidogrel that was sold in the U.S. in August 2006 (more than two years before the  
commencement of Sanofi’s action in June 2009).  
[245] In response, Sanofi argues that section 55.01 of the Patent Act, which provides for a six-year  
limitation period, should apply. This section reads as follows:  
Limitation  
Prescription  
55.01 No remedy may be  
awarded for an act of  
infringement committed more  
than six years before the  
commencement of the action  
for infringement.  
55.01 Tout recours visant un  
acte de contrefaçon se prescrit à  
compter de six ans de la  
commission de celui-ci.  
Page: 83  
[246] Alternatively, Sanofi claims that subsection 39(2) of the Federal Courts Act, which also  
provides for a six-year limitation period, could also apply because the cause of action arose  
otherwise than in a province. Subsection 39(1) and 39(2) of the Federal Courts Act provide as  
follows:  
Prescription and limitation on  
proceedings  
Prescription - Fait survenu dans  
une province  
39. (1) Except as expressly  
39. (1) Sauf disposition  
provided by any other Act, the  
contraire d’une autre loi, les  
laws relating to prescription and règles de droit en matière de  
the limitation of actions in force prescription qui, dans une  
in a province between subject  
and subject apply to any  
proceedings in the Federal  
Court of Appeal or the Federal  
province, régissent les rapports  
entre particuliers s’appliquent à  
toute instance devant la Cour  
d’appel fédérale ou la Cour  
Court in respect of any cause of fédérale dont le fait générateur  
action arising in that province.  
est survenu dans cette province.  
Prescription and limitation on  
Prescription - Fait non survenu  
proceedings in the Court, not in dans la province  
province  
(2) A proceeding in the Federal (2) Le délai de prescription est  
Court of Appeal or the Federal  
Court in respect of a cause of  
de six ans à compter du fait  
générateur lorsque celui-ci n’est  
action arising otherwise than in pas survenu dans une province.  
a province shall be taken within  
six years after the cause of  
action arose.  
[247] Sanofi’s position is based on the contention that Apotex’ global enterprise in respect of  
clopidogrel resulting in the infringement of the ‘777 Patent cannot be said to be confined to a single  
province. Moreover, Sanofi contends that Apotex arranged for and imported bulk clopidogrel  
bisulfate from […] and exported clopidogrel bisulphate tablets to numerous countries, including the  
U.S.  
Page: 84  
[248] While the current Patent Act contains an explicit limitation provision at section 55.01 of the  
Patent Act, the ‘777 Patent is an “Old Act” patent. Under the transitional provisions in s 78.2 of the  
Act “any matter” in relation to validity or infringement falls to be determined under the provisions  
of the Act as it read immediately before October 1, 1989 and none of these provisions contains a  
limitation period. As emphasized by Apotex, section 55.01 of the Patent Act does not apply to an  
“Old Act” patent and does not therefore apply in the present case. In the present case, the default  
provisions of section 39 of the Federal Courts Act are applicable.  
[249] As a result, the Court must now determine if the cause of action took place only in the  
province of Ontario or if it took place elsewhere. This will allow the Court to establish which of  
subsection 39(1) or subsection 39(2) applies in the circumstances. The Court recalls that in order for  
subsection 39(1) of the Federal Courts Act to apply, all of the elements of the cause of action must  
have arisen in the subject province, in this case, Ontario.  
[250] In Apotex Inc. v Pfizer Canada Inc., 2004 FC 190, 31 CPR (4th) 143, the Federal Court  
provided an indication as to what could be considered “otherwise than in a province”. It observed at  
paras 14 and 15 that “both the damages suffered as well as the act that caused the damage must  
necessarily have arisen in the particular province: Markevich v. Canada (2003), 223 D.L.R. (4th)  
17, at 35 and 36 (S.C.C.); Kirkbi A.G. v. Ritvik Holdings Inc. (2002), 20 C.P.R. (4th) 224 at 284  
(F.C.T.D.); Canada v. Maritime Group (Canada) Inc. (1995), 185 N.R. 104 at 106 (F.C.A.);  
Gingras v. Canada (1994), 113 D.L.R. (4th) 295 at 319 (F.C.A.)”. It further observed that in that  
case “the proceeding allegedly led to lost sales and the inappropriate continuation of a monopoly in  
Pfizer’s favour throughout Canada, and not within any particular province”.  
Page: 85  
[251] In the present case, Sanofi submits that Apotex arranged for and imported bulk clopidogrel  
bisulfate from […] and exported clopidogrel bisulphate tablets to numerous countries, including the  
U.S. Moreover, Sanofi emphasizes that to carry out this enterprise, Apotex employed numerous  
agents including Apotex Corp, Apotex Australia, Apotex New Zealand, Apotex India and Apotex  
Pharmachem. In addition, Sanofi points to the fact that Apotex Pharmachem acted as agent for […]  
for filings in many countries including Hungary, Canada, Australia, New Zealand and the U.S. In  
support of its position, Sanofi further relies on the testimony of Mr. John Hems, Director of  
regulatory intelligence at Apotex, who testified about the various agency relationships at issue. The  
evidence demonstrates that there have been submissions made to different regulatory agencies  
abroad, including the FDA in the U.S. (Hems, cross T1148-1149, 1161-1162).  
[252] Sanofi also relies on the testimony of Mrs. Antoniette Walkom, VP of Quality Assurance  
and Regulatory Affairs at Apotex Pharmachem, [omitted]:  
Q. [omitted]?  
A. [omitted].  
Q. [omitted]?  
A. [omitted].  
Q. [omitted]?  
A. [omitted].  
Q. [omitted]?  
A. [omitted].  
Q. [omitted]?  
A. [omitted].  
Q. [omitted]?  
A. [omitted].  
[253] As previously noted, the evidence before the Court reveals that Apotex arranged for and  
imported bulk clopidogrel bisulfate from […] and exported clopidogrel bisulfate to numerous  
countries. This evidence on its own is sufficient to conclude that infringement in this case was not  
Page: 86  
limited to the confines of a single province and it is well established that importation into Canada of  
a patented product constitutes infringement (see Schmeiser, above, at para 44).  
[254] The Court further notes that for customs purposes, the importer is the party who has title to  
the goods at the time the goods are transported into Canada. In the case at bar, the evidence  
demonstrates that Apotex represented itself as the “importer” in respect of the goods acquired from  
[…] and as an “exporter” with regards to the international sales.  
[255] In addition, the Court also agrees with Sanofi that because […] manufactures exclusively for  
Apotex and to Apotex’ specifications, title in the goods passed once they were in a deliverable state.  
Indeed, title may pass upon manufacture but passes at the latest at the time of delivery to the first  
carrier in […] (W. Tetley, Marine Cargo Claims, 4th Ed., Éditions Yvon Blais, 2008, pp. 400-40).  
In this regard, the Court recalls the cross-examination of Jose Miguel Lazcano Seres, Technical  
Director at […], who testified about contracts and shipping documents between […] and Apotex.  
According to Sanofi, the use of the term CIF is a further indication of the passing of title and risk no  
later than delivery to the first carrier.  
[256] It is also relevant that Apotex did not show what became of any remaining goods once the  
injunction was issued in the U.S. and whether these goods were shipped back to Canada.  
[257] Finally, the following additional elements demonstrate that Apotex’ activities and the  
resulting cause of action, in this case, cannot be confined to a single province:  
!
Apotex conducts business and has places of business in other  
provinces;  
Page: 87  
!
!
!
Pharmachem advertises the sale of clopidogrel on its website  
which reaches beyond Ontario;  
Apotex entered into agreements and accepted purchase orders in  
Canada from foreign entities; and  
Apotex has engaged an Indian manufacturer to assist in the  
manufacture of its product and has shipped bulk API to India.  
[258] In light of the foregoing, the Court concludes that the damages suffered as a result of  
Apotex’ infringement cannot be limited to a particular province as the cause of action arose  
otherwise than in a single province. This proceeding will allegedly lead to lost sales and the  
inappropriate continuation of a monopoly in Sanofi’s favour throughout Canada, and not within any  
particular province. The factual elements put forward by Sanofi in this regard cannot be considered  
as purely incidental factors. Thus, subsection 39(2) of the Federal Courts Act applies and none of  
the claims in respect of Apotex’ activities are statute barred.  
(2) The Settlement Agreements and Estoppel Defence  
[259] A further defence raised by Apotex concerns the Settlement Agreements signed in March  
and May 2006. Assessing the merits of this defence requires an examination of these Settement  
Agreements.  
The Circumstances having led to the Settlement Agreements  
[260] The circumstances in which the March and May 2006 Settlement Agreements were reached  
can be summarized as follows.  
[261] On November 21, 2001, Apotex filed an ANDA for Apo-clopidogrel with the U.S. Food and  
Drug Administration (FDA) and an accompanying certification that the U.S. counterpart to the ‘777  
Page: 88  
Patent, U.S. Patent No. 4,487,265 (the ‘265 Patent), was invalid and would not be infringed by the  
Apo-clopidogrel formulation. Because Apotex was the first generic company to so certify, under  
U.S. law, it was entitled to sell its drug without other generic competition for 180 days upon  
receiving approval.  
[262] On March 21, 2002, Sanofi/BMS commenced an action against Apotex in the U.S. District  
Court (File No. 02-CV-2255) for infringement of the ‘265 Patent (the “U.S. Clopidogrel Action”).  
With the commencement of the U.S. Clopidogrel Action, there was a statutory stay which  
prohibited the FDA from granting final approval to Apotex’ ANDA before May 17, 2005, unless  
the U.S. Clopidogrel Action was determined against Sanofi/BMS before that time.  
[263] On October 24, 2005, given that the statutory stay had expired and the action had not  
reached trial, Apotex wrote to Sanofi/BMS to confirm Apotex’ intention to launch immediately  
upon regulatory approval. In its letter, Apotex also confirmed that it had been investing and  
continued to invest heavily in production for launch.  
[264] On January 20, 2006, the FDA approved Apotex’ ANDA. Around the same time, the parties  
commenced settlement discussions. The commercial context of these negotiations was explained by  
Dr. Sherman in his testimony. At the time, the U.S. clopidogrel market for Plavix was worth $4  
billion per annum. Accordingly, a launch by Apotex coupled with an adverse ruling as to the  
validity of the ‘265 Patent put Sanofi/BMS at risk of losing in excess of $25 billion over the  
remaining life of the ‘265 Patent. From Apotex’ perspective, the risks were significant too: It had  
already invested significantly in inventory in preparation for launch and, despite having advised  
Page: 89  
Sanofi of this, no motion for an interlocutory injunction had been brought. A launch at risk by  
Apotex, coupled with a successful motion for an interlocutory injunction would have the immediate  
effect of precluding further sales by Apotex, while dissipating the enormous value to Apotex of the  
one hundred and eighty (180)-day exclusivity period (which period would continue to run despite  
any interlocutory injunction). Furthermore, if Apotex launched at risk and ultimately lost at trial, it  
would face the prospect of treble damages that are available under U.S. law.  
[265] These factors are significant for the purpose of properly understanding the Settlement  
Agreements that ultimately ensued. Clearly, both sides faced enormous risks going into the  
negotiations and clearly each side would be interested in attenuating those risks.  
[266] Accordingly, during the initial negotiations, the primary focus of both parties was to  
conclude a settlement whereby Sanofi/BMS would conserve the value of its unexpired patent for as  
long as possible while Apotex would defer its one hundred and eighty (180)-day exclusivity until  
the end of the patent term. This was to be accomplished by a six (6)-month license in favour of  
Apotex at the end of the patent term.  
[267] However, during the negotiations, Sanofi/BMS advised Apotex that they were under consent  
decrees with the Federal Trade Commission (FTC) and the Attorneys General of some of the states  
in the U.S. that prevented them from entering into patent settlements without prior approval. As a  
result of this, Apotex demanded and Sanofi/BMS agreed to concessions to Apotex if the settlement  
was submitted to the regulators but was not approved by them. The concessions were, first, that, in  
the event of regulatory denial, Apotex would have a period of time within which to sell off its  
Page: 90  
inventory (i.e. without facing the prospect of a motion for an interlocutory injunction) and, second,  
that, in the event that the action proceeded to trial with Apotex having launched at risk, Apotex  
would be guaranteed a profit in respect of its sales by way of an agreement to a fixed level of  
damages that would be less than Apotex’ profits.  
The March 2006 Agreement  
[268] The March 2006 Agreement was signed on March 17, 2006, wherein Sanofi and Apotex  
agreed to settle the litigations between them involving the ‘265 U.S. Patent. The main terms of the  
agreement were the following:  
!
that the pending litigations between Apotex and Sanofi be  
terminated and that Apotex release all claims that it brought or  
could have brought against Sanofi in connection with these  
litigations;  
!
that Apotex be granted an exclusive six-month license under the  
‘265 Patent, effective September 17, 2011, to make, use, import,  
sell and offer for sale its clopidogrel bisulfate ANDA product in  
the United States, without the right to grant sub-licenses,  
provided that Sanofi obtain pediatric exclusivity for the product  
by March 1, 2011;  
!
!
that Apotex’ license could be triggered at an earlier date  
depending on Apotex’ sole market exclusivity for clopidogrel  
bisulfate under 21 U.S.C. § 355(j)(5);  
that Apotex inform Sanofi of any event that could constitute a  
trigger of every basis on which Apotex would have sole  
clopidogrel bisulfate under the Hatch-Waxman Act, in which  
case Sanofi could elect to accelerate the effective date of  
Apotex’ license;  
!
!
that Apotex pay to Sanofi a royalty of 1% of its net sales on all  
sales of its clopidogrel bisulfate product in the United States  
during the period of Apotex’ exclusivity;  
that Apotex refrain from selling any clopidogrel product in the  
United States prior to the date its license under the ‘265 Patent  
Page: 91  
became effective; that Sanofi reimburse Apotex for their  
investment in inventory;  
!
!
that Sanofi attempt to obtain a release of any claims that […]  
could have against Apotex pursuant to the contract signed  
between […] and Apotex dated June 30, 2000; and  
that Sanofi compensate Apotex in the event that certain  
minimum annual U.S. sales of Plavix could not be met and the  
understanding that no other license was to be granted under any  
other patent owned or controlled by Sanofi.  
[269] The parties also agreed that the agreement was subject to a regulatory review and provided  
for alternate terms in the event of any regulatory denial by the FTC and state Attorneys General.  
[270] On or about May 4, 2006, the parties were advised by the state Attorneys General that  
approval of the March 2006 Agreement was denied.  
[271] Notwithstanding the failure to secure regulatory approval, both parties confirmed, by their  
actions and words, their continuing desire to mitigate their commercial risks as they engaged in  
further negotiations in an attempt to modify the March 2006 Agreement to deal with the provisions  
that were understood to be of concern to the regulators.  
The May 2006 Agreement  
[272] Following further negotiations, the parties signed a second Settlement Agreement dated May  
26, 2006, with a number of amendments, including a modification in the damages stipulation from  
70% to 50% of Apotex’ net sales. Sanofi and Apotex agreed to settle the litigations between them  
involving the ‘265 U.S. Patent. The main terms of the agreement were the following:  
Page: 92  
!
!
that the pending litigations between Apotex and Sanofi be  
terminated and that Apotex release all claims that it brought or  
could have brought against Sanofi in connection with these  
litigations;  
that Apotex be granted a license, under the ‘265 Patent, effective  
June 1, 2011 to make, use, import, sell, and offer for sale its  
clopidogrel bisulfate ANDA product in the United States,  
without the right to grant sub-licenses; in the event that Sanofi  
could not obtain pediatric exclusivity for its clopidogrel bisulfate  
product by March 15, 2011, Apotex’ license would become  
effective on April 1, 2011;  
!
that in the event that Sanofi launched a drug product other than  
Plavix (with an antiplatelet aggregation agent as an active  
ingredient) in the United States prior to the effective date of  
Apotex’ license under the ‘265 Patent, that Apotex be granted a  
license under that drug product as well;  
!
!
that Apotex’ license could be triggered at an earlier date  
depending on Apotex’ sole market exclusivity for clopidogrel  
bisulfate under 21 U.S.C. § 355(j)(5);  
that Apotex inform Sanofi of any event that could constitute a  
trigger of every basis on which Apotex would have sole  
clopidogrel bisulfate under the Hatch-Waxman Act, in which  
case Sanofi could elect to accelerate the effective date of  
Apotex’ license;  
!
that Apotex refrain from selling any clopidogrel product in the  
United States prior to the date that its license under the ‘265  
Patent becomes effective;  
!
!
that Sanofi reimburse Apotex for their investment in inventory;  
that Sanofi attempt to obtain a release of any claims that […] had  
against Apotex pursuant to the contract signed between […] and  
Apotex dated June 30, 2000; with the parties’ understanding that  
no other license was to be granted under any other patent owned  
or controlled by Sanofi.  
[273] Again, the parties also agreed that the agreement was subject to a regulatory review and  
provided for alternate terms in the event of any regulatory denial by the FTC and state Attorneys  
Page: 93  
General. As such, regulatory approval was not forthcoming. On or about the end of July 2006,  
Apotex declared regulatory denial pursuant to paragraph 13 of the May 2006 Agreement.  
[274] Apotex accordingly proceeded to launch Apo-clopidogrel in the U.S. on or about August 8,  
2006. Sanofi/BMS responded by attempting to obtain a temporary restraining order on August 4,  
2006 which was refused by Stein J. of the United States District Court – Southern District of New  
York – because of the provisions of paragraph 15 of the May 2006 Agreement.  
[275] However, Sanofi/BMS was successful in its subsequent attempt to secure a preliminary  
injunction pending trial on August 31, 2006. After a trial, Justice Stein rendered a judgment  
upholding the validity of the ‘265 Patent. In subsequent proceedings, Justice Stein fixed on October  
19, 2010 Sanofi/BMS’ damages in respect of sales of the U.S. Apo-clopidogrel in the amount of  
U.S. $442,209,362, which represents 50% of the net sales of the U.S. Apo-clopidogrel. In  
November 2010, Apotex paid into the Court a net amount of U.S. $556,000,000 in respect of the  
judgment, plus interest and cost.  
The Case at Bar  
[276] Apotex submits that Sanofi/BMS is precluded from recovering in respect of any of the U.S.  
Apo-clopidogrel found to be infringing because of these two agreements and more particularly  
because of paragraph 14 of the May 2006 Agreement which fixed Sanofi’s damages in connection  
with any sale of the U.S. Apo-clopidogrel at 50% of Apotex’ net sales of same. Thus, Apotex  
claims that subparagraph 14(ii) prevents any further recovery in this case. In other words, Apotex  
claims that the Settlement Agreements preclude Sanofi/BMS from circumventing the bargain they  
Page: 94  
struck in March and May 2006 by coming to Canada to sue Apotex and recover a second time for  
the same Apo-clopidogrel in respect of which they have already secured judgment and payment in  
the U.S. Apotex’ understanding of the Agreement is that the “Liability Exposure Provision” (para  
14 ii) of the May 2006 Agreement) expressly precludes any claim outside the U.S. litigation for  
relief in respect of the U.S. sales of infringing clopidogrel bisulfate.  
[277] In contrast, Sanofi argues that this alleged defence on the part of Apotex hinges on the  
incorrect premise that the U.S. litigation and U.S. Settlement Agreements extend to this action and  
the ‘777 Patent. Assessing the merits of this defence requires an examination of the Settlement  
Agreements between Apotex and Sanofi and their submissions.  
[278] Sanofi considers that there is no ambiguity and that the Agreements are clear that they are  
expressly limited to the U.S. litigation under the U.S. Patent.  
[279] Based on the terms of the Settlement Agreements, and in particular the Liability Limitation  
Provision, the Court is of the view that Apotex is not absolved of any liability arising from the  
infringement of the ‘777 Patent. The Court considers that there is no ambiguity in the Settlement  
Agreements and that the parties’ intentions are clear on the face of these Agreements. In the absence  
of any ambiguity in the terms of a written contract, the parties must be held to the literal meaning of  
such terms (Eli Lilly & Co. v Novopharm Ltd., [1998] 2 SCR 129 at pp 166-167; G.H.L. Fridman,  
“The Law of Contract in Canada”, (Thomson Canada Limited, 2006) at 454).  
Page: 95  
[280] In the case at bar, there is simply no mention of the words “ ‘777 Patent ” or “Canada” in the  
Settlement Agreements nor can any implied term to this effect be read into the Settlement  
Agreements, given that they are expressly limited to the U.S. litigation under the ‘265 U.S. Patent.  
Indeed, page one of both the Settlement Agreements leaves no room for doubts in this regard:  
Sanofi and Apotex agree to settle the litigations between them involving  
the U.S. Patent No. 4,847,265. 02CV-2255 and 05CV-3965, on the  
following terms: […]  
(May 2006 U.S. Settlement Agreement  
March 2006 U.S. Settlement Agreement)  
[281] Further, the Agreements make explicit references to the ‘265 Patent (U.S. Patent) whilst  
remaining void of any explicit reference to the ‘777 Patent or to Canada (e.g. paras 4 and 14). In the  
face of such clear and unambiguous references, the Court does not consider it apposite to assess  
extrinsic evidence on this point (Eli Lilly v Novopharm, at para 166).  
[282] Whilst Apotex may not be satisfied with the outcome of the Settlement Agreements, it is not  
open to Apotex to ask the Court to depart from the clear language of these Agreements and to read  
into them the words “ the ‘777 Patent” or “Canada” into the Agreements. Query: Does Apotex’  
logic means that Settlement Agreements of March and May 2006 also make implied reference to  
other patents in other foreign jurisdiction?  
[283] The fact that, from Apotex’ point of view, the Agreements may produce undesirable effect is  
not sufficient to allow the Court to decide otherwise (General Motors of Canada Ltd. v Canada,  
2008 FCA 142, 292 DLR (4th) 331 [General Motors]). The Court would add that Apotex, a  
Page: 96  
sophisticated party in the field of pharmaceutical litigation and negotiations, must be held to the  
clear terms of the bargain it reached under the Settlement Agreements.  
[284] Finally, the Court further recalls that Apotex also raised the defences of estoppel and abuse  
of process in reference to the Settlement Agreements.  
[285] With respect to estoppel, Apotex submits that, under this principle, Sanofi is precluded from  
pursuing in this action what is, according to Apotex, a second claim for compensation in respect of  
the very same manufacture and sale of the U.S. APO-clopidogrel.  
[286] Moreover, Apotex argues that the monetary judgment in the U.S. Clopidogrel Action was  
secured on the basis of a contractual arrangement between the parties pursuant to which they  
stipulated as to what is essentially a factual matter (the measure of Sanofi’s “actual damages” in the  
event of a launch at risk by Apotex in the U.S. and subsequent finding that the ‘265 Patent was valid  
and infringed). It follows, says Apotex, that Sanofi would be claiming damages in Canada on the  
same pills that were sold in the U.S. and were the subject of a damages award by Justice Stein of the  
United States District Court – Southern District of New York.  
[287] Apotex also submits that if Sanofi is able to obtain an accounting of profits, they will be able  
to recoup the 50% that they negotiated away in the March and May 2006 Agreements. Because  
Apotex claims to have proceeded to act in reliance of that stipulation, Apotex argues that Sanofi  
should be estopped from attempting to circumvent that stipulation.  
Page: 97  
[288] An estoppel defence operates to preclude a party from relitigating the same cause of action  
twice (Danyluk v Ainsworth Technologies Inc., 2001 SCC 44, [2001] 2 SCR 460, at paras 18 and  
54). In Toronto (City) v Canadian Union of Public Employees (C.U.P.E.), Local 79, 2003 SCC 63,  
[2003] 3 SCR 77, at para 23, the Supreme Court of Canada held that three (3) preconditions must be  
met for estoppel to be successfully invoked:  
[23] …(1) the issue must be the same as the one decided in the prior  
decision; (2) the prior judicial decision must have been final; and (3) the  
parties to both proceedings must be the same, or their privies (Danyluk v  
Ainsworth Tech., 2001 SCC 44, [2001] 2 SCR 460, 2001 SCC 44, at para  
25, per Binnie J.) The final requirement, known as “mutuality”, has been  
largely abandoned in the United States and has been the subject of much  
academic and judicial debate there as well as in the United Kingdom and, to  
some extent, in this country. (See G.D. Watson, “Duplicative Litigation:  
Issue Estoppel, Abuse of Process and the Death of Mutuality” (1990), 69  
Can. Bar. Rev. 623 at pp. 648-51.) …  
[289] Res judicata is essentially premised on the notion that a matter has already been adjudged  
and is founded on the principles that a party shall not be vexed twice for the same complaint and  
that there is a societal value in the finality and conclusiveness of judicial decisions (see Angle v  
Canada (Minister of National Revenue), [1975] 2 SCR 248, at para 267; CPU Options, Inc. v  
Milton (2006), 79 OR (3d) 365, at para 15 (SCJ)).  
[290] Against this background, the Court is not able to accede to Apotex’ alleged estoppel defence  
because the U.S. litigation and the Agreements simply did not deal with infringement or the validity  
of the ‘777 Patent. It is therefore not open for the Court to conclude that the issue is the same as the  
one decided in the Agreements. The Court accordingly agrees with Sanofi that, where the legal  
rights upon which a cause of action is based were not adjudicated in the previous proceeding, the  
estoppel principle does not apply.  
Page: 98  
[291] Apotex has also raised the issue of abuse of process. In common law, judges have an  
inherent and residual discretion to prevent an abuse of the Court’s process (CUPE, above, at para  
35). However, the Court has not been convinced that this case boils down to a question of abuse of  
process. On the basis of the evidence and for the reasons mentioned above, the Court remains  
unpersuaded that Sanofi is using the courts for an improper use and that the integrity of the court’s  
process is at issue in this case.  
[292] Thus, for all of these reasons, the defences raised by Apotex fail.  
G.  
Conclusion  
[293] Subject to the validity of the patent and the defences that were pleaded by Apotex, there can  
be no question that Apotex has infringed the claims of the ‘777 Patent. However, there is no need at  
this time for the Court to assess and award damages as the Court has found the ‘777 Patent to be  
invalid for lack of utility and obviousness. The Court will now proceed to the issue of validity of the  
‘777 Patent.  
VII  
Validity  
[294] Section 45 of the Patent Act provides that a patentee benefits from a presumption of validity.  
The burden in this case is on Apotex to convince the Court, on a balance of probabilities, that the  
‘777 Patent is invalid. The question of the validity of the ‘777 Patent raises, in this case, the  
following issues:  
Page: 99  
!
!
!
!
!
overbreadth;  
sufficiency;  
anticipation;  
double patenting; and  
utility.  
A.  
Overbreadth  
[295] If a claim encompasses more than what the inventor actually accomplished or what the  
inventor actually disclosed, such a claim is invalid. The claims cannot be broader that the invention  
disclosed (Apotex Inc. v Hoffmann-La Roche Ltd. (FCA), [1989] FCJ No 321, 24 CPR (3d) 289).  
[296] On the basis of this principle, Apotex alleges that Claim 6 of the ‘777 Patent is overbroad  
because it encompasses processes that were not invented.  
[297] In order to determine whether Claim 6 of the ‘777 Patent is overbroad, the Court must first  
look at the claims at issue.  
[298] The Court observes that Claim 6 of the ‘777 Patent states the process to obtain clopidogrel.  
Apotex argues that Claim 6 contains no restriction to a particular resolving agent or solvent. The  
Court recalls that Claim 6 includes the use of optically active acids and solvents that result in the  
preparation of substantially pure clopidogrel and its pharmaceutically acceptable salts following the  
process described in Claim 6 (para 107). The Court therefore cannot agree with Apotex because  
Claim 6 cannot be dissociated from Claims 7, 8 and 9 (see construction of Claim 6 in section F).  
The Court cannot therefore agree with Apotex that Sanofi has claimed every possible chiral agent  
and solvent.  
Page: 100  
[299] Apotex also alleges the issue of purity and the lack of a purity limitation relating to the  
dextro-rotatory and the levo-rotatory.  
[300] The Court recalls that one of the derivatives claimed in the ‘875 Patent is PCR 4099 which  
is composed from 50% of dextro-rotatory clopidogrel and 50% levo-rotatory clopidogrel. Hence,  
Apotex argues that the claims of the ‘777 Patent do not contain a purity limitation. According to  
Apotex’ submission, it would follow that if someone makes PCR 4099 it would be clopidogrel with  
a 50% impurity and, as a result, this would fall within the claims of the ‘777 Patent, absent a  
limitation for purity. Apotex accordingly submits that the specification of the ‘777 Patent does not  
distinguish in sufficient terms the subject matter of the invention and, for this reason, is thus invalid  
for overbreadth.  
[301] It is significant that no witnesses testified to the fact that the claim is broad enough to  
encompass PCR 4099. The evidence does not indicate that clopidogrel would encompass the  
racemate. The disclosure of the ‘777 Patent indicates a purity of at least 96% for the dextro-rotatory  
enantiomer and at least 98% for the levo-rotatory enantiomer. Moreover, the testimony of Dr.  
Adger, Dr. Hirsh, and Dr. Byrn further confirms that expert witnesses agree to construe the claim as  
substantially pure. The Court accordingly cannot find overbreadth in relation to the purity of the  
claims in the ‘777 Patent.  
[302] For all of these reasons, the Court finds that a person skilled in the art would construe the  
claims of the ‘777 Patent as substantially pure. The Court accordingly concludes that Apotex’  
allegations of overbreadth are unfounded.  
Page: 101  
B
Sufficiency  
[303] “Sufficiency” means that the patent’s disclosure meets the requirements set out in section 34  
of the Patent Act. The specification in the patent application must allow a person skilled in the art to  
replicate the invention, as claimed.  
[304] Apotex alleges that the ‘777 Patent does not disclose sufficient information for the POSITA  
to put the invention into practice. Yet, in the case at bar, there was no evidence at trial that supported  
this position in a substantial manner. The invention exists and it can be put into practice with the  
information contained within the patent.  
[305] In sum, Apotex’ allegation of insufficiency is rejected by the Court.  
C.  
Anticipation  
(1) General Principles  
[306] In his decision in Abbott Laboratories v Canada (Minister of Health), 2008 FC 1359, 71  
CPR (4th) 237, at para 75, Justice Hughes sets out the legal requirements to be considered for  
anticipation:  
[75] To summarise the legal requirements for anticipation as they apply to the  
circumstances of this case:  
1. For there to be anticipation there must be both disclosure and  
enablement of the claimed invention.  
2. The disclosure does not have to be an “exact description” of the  
claimed invention. The disclosure must be sufficient so that when  
read by a person skilled in the art willing to understand what is being  
said, it can be understood without trial and error.  
Page: 102  
3. If there is sufficient disclosure, what is disclosed must enable a  
person skilled in the art to carry out what is disclosed. A certain  
amount of trial and error experimentation of a kind normally expected  
may be carried out.  
4. The disclosure when carried out may be done without a person  
necessarily recognizing what is present or what is happening.  
5. If the claimed invention is directed to a use different from that  
previously disclosed and enabled then such claimed use is not  
anticipated. However if the claimed use is the same as the previously  
disclosed and enabled use, then there is anticipation.  
6. The Court is required to make its determinations as to disclosure  
and enablement on the usual civil burden of balance and probabilities,  
and not to any more exacting standard such as quasi-criminal.  
7. If a person carrying out the prior disclosure would infringe the  
claim then the claim is anticipated.  
[307] In the present case, the threshold issue is whether the “publications” presented to the Court  
can be considered in the anticipation analysis.  
[308] The relevant date for anticipation is two (2) years prior to the filing date. The filing date is  
February 8, 1988 and, therefore, the relevant date for whether prior art can be considered in the  
anticipation analysis is February 8, 1986. In order for the Court to find anticipation, it needs to look  
back and see if the invention is disclosed.  
[309] Under the Old Patent Act, the law of anticipation is based upon the former section 27 of the  
Patent Act. As correctly indicated by Sanofi, under section 27 of the Old Act, the invention must not  
have been described in any patent or in any publication printed in Canada or in any other country  
more than two (2) years before the Canadian patent application filing. According to Apotex,  
subsection 27(1)(b) of the Old Act is the provision relevant for the case at bar. Subsection 27(1)(b)  
of the Old Patent Act states the following:  
Page: 103  
27. (1) Subject to this section,  
27. (1) Sous réserve des autres  
any inventor or legal  
dispositions du présent article,  
representative of an inventor of l’auteur de toute invention ou le  
an invention that was  
représentant légal de l’auteur  
d’une invention peut, sur  
…
présentation au commissaire  
(b) not described in any patent d’une pétition exposant les  
or in any publication printed  
in Canada or in any other  
country more than two years  
before presentation of the  
faits, appelée dans la présente  
loi le « dépôt de la demande »,  
et en se conformant à toutes les  
autres prescriptions de la  
petition hereunder mentioned, présente loi, obtenir un brevet  
and  
qui lui accorde l’exclusive  
propriété d’une invention qui  
n’était pas :  
…
may, on presentation to the  
Commissioner of a petition  
setting out the facts, in this Act,  
termed the filing in the  
application, and on compliance  
with all other requirements of  
this Act, obtain a patent  
[…]  
b) décrite dans un brevet ou  
dans une publication  
imprimée au Canada ou dans  
tout autre pays plus de deux  
ans avant la présentation de la  
pétition ci-après mentionnée;  
granting to him an exclusive  
property in the invention.  
[…]  
[310] Thus, only that which is described in printed publications more than two years before the  
Canadian filing date can be considered.  
[311] In this regard, Apotex alleges that there were several posters and abstracts that “anticipated”  
the invention in the ‘777 Patent. In addition, Apotex alleges that the ‘875 Patent disclosed the  
invention in the ‘777 Patent.  
(2) The Posters and the Abstracts  
Page: 104  
[312] A number of exhibits were filed before the Court by Apotex with respect to anticipation of  
the ‘777 Patent. These exhibits relate to abstracts presented at international conferences as well as  
posters.  
[313] The Court will first address the issue of the posters.  
[314] In the case at bar, the evidence overwhelmingly demonstrates that the posters referred to by  
Apotex were not published in the books of abstracts or in any other publication. Therefore, they do  
not meet the requirements of subsection 27(1)(b) as they do not constitute publications. Dr. Hirsh  
confirmed that posters would not be in the book of abstracts because an individual will normally  
bring a poster to a conference meeting. He also testified that posters would not end up in a scientific  
library. Dr. Sanders agreed that posters were not part of the abstracts. Dr. Colman stated that unless  
posters were given out, a participant would not have a copy and Dr. Byrn confirmed that posters  
were not printed. Dr. Shebuski confirmed that abstracts were published but not posters. Dr.  
Shebuski also added that “as soon as you’re done presenting the poster, you throw it in the trash can  
and you leave town”. On the basis of this evidence before the Court in the present case, posters are  
therefore discarded as part of the anticipation analysis.  
[315] The Court will now focus on the pertinent published abstracts.  
Abstract #1  
[316] The first abstract is from Maffrand et al entitled “Animal Pharmacology of PCR 4099, A  
New Thienopyridine Compound” published in “Thrombosis and Haemostasis” – the Journal of the  
Page: 105  
International Society of Haemostasis and Thrombosis. It is dated January 10, 1986. Thus, it meets  
the requirements of subsection 27(1)(b).  
[317] This abstract makes reference to PCR 4099. It provides the chemical name and indicates that  
it has been evaluated in rats and baboons. There is mention of three (3) types of thrombosis induced  
in rats and that PCR 4099 exhibits the same broad spectrum of antiaggregating effect as ticlopidine  
in animals but it is forty (40) times more potent in rats and ten (10) times in baboons.  
[318] It is worthy of note that the abstract does not mention the word “enantiomers” and there is  
no mention of chirality. There is no compound structure to be found either. There is no drawing in  
this abstract. There is no information concerning differential activity or differential toxicity. Further,  
the abstract does not specifically disclose or teach the hydrogen sulfate salt of clopidogrel, or how to  
obtain the dextro-rotatory enantiomer, or their unique and valuable combination of properties. There  
is nothing in this abstract that would lead a skilled person in the art to resolve PCR 4099  
enantiomers, prepare the hydrogen sulfate salt of clopidogrel, or suspect that it had unique  
advantages over other salts, the racemate, and the other enantiomer. As noted by Dr. Byrn, and the  
Court agrees, the comments regarding the potency of PCR 4099 as compared to that of ticlopidine  
would lead a skilled chemist away from looking for new compounds with unknown properties such  
as the enantiomers.  
[319] Thus, this abstract does not disclose the invention in the ‘777 Patent.  
Page: 106  
Abstract #2  
[320] The second abstract is from Thebault et al entitled “PCR 4099 – A New Thienopyridine  
Derivative with Potent Anti-Platelet Activity in Man”. It is dated July 14, 1985. The abstract does  
not contain any process information related to the contents of the ‘777 Patent. It states that the  
racemate PCR 4099 works well. Again, there is no reference to the specific structure of PCR 4099.  
The abstract states that PCR 4099 exhibits potent antiplatelet activity in man, provides certain test  
data and indicates that PCR 4099 was well-tolerated both clinically and biologically. It indicates  
that further studies are planned in order to assess the dose effect relationship to the compound. The  
abstract is silent with regard to the salts.  
[321] Thus, this abstract does not disclose the invention in the ‘777 Patent.  
Abstract #3  
[322] The third abstract, entitled “PCR 4099 – A New Antithrombotic drug – Evaluation of  
Tolerance and of Pharmacological Activity”, is dated June 1986. It is published less than two (2)  
years prior to the date of filling (February 8, 1988) and cannot be relied upon by the Court for the  
purposes of anticipation.  
(3) The ‘875 Patent  
[323] The Court will now address the ‘875 Patent in the context of anticipation.  
[324] The Court recalls that the ‘875 Patent was filed in Canada on July 8, 1983 and issued on  
October 8, 1985.  
Page: 107  
[325] The ‘875 Patent discloses as part of its general teaching a very broad class of thienopyridine  
derivatives defined by a general formula. In addition, the ‘875 Patent discloses twenty-one (21)  
specific compounds within this general formula. Dr. Byrn and Dr. Davies testified that clopidogrel  
or its bisulfate salt is not one of these compounds. Upon reading the patent, the Court agrees with  
Dr. Byrn and Dr. Davies that the ‘875 Patent does not disclose a method for preparing any  
enantiomers nor does it disclose its advantages or the bisulfate salts. The claimed invention of the  
‘777 Patent is not disclosed by the ‘875 Patent.  
[326] More specifically, the ‘875 Patent does not:  
!
disclose clopidogrel or any pharmaceutically acceptable salt of  
clopidogrel of Claim 1;  
!
!
!
!
!
!
disclose the bisulfate salt of clopidogrel of Claim 3;  
disclose any of the specific salts of Claims 2-5;  
disclose the process of Claims 6-9;  
disclose the pharmaceutical compositions of Claim 10-11;  
disclose the beneficial properties of clopidogrel;  
disclose the beneficial properties of the claimed salts of  
clopidogrel; and  
!
teach how to make the invention of the ‘777 Patent.  
[327] Thus, the ‘875 Patent does not disclose the invention in the ‘777 Patent.  
[328] Consequently, on this issue, the Court arrives at the same conclusion as the Supreme Court  
of Canada’s decision in Plavix, at para 41:  
[41] Since the ‘875 patent did not disclose the special advantages of  
the dextro-rotatory isomer and of its bisulfate salt, as compared to the  
levo-rotatory isomer or the racemate and their salts, or the other  
compounds made and tested or otherwise referred to in the ‘875  
patent, the invention of the ‘777 patent cannot be said to have been  
disclosed and therefore it cannot be said to have been anticipated.  
Page: 108  
[329] In light of the above, it is not necessary to consider enablement since anticipation requires  
proof of both disclosure and enablement (Plavix, para 42).  
(4) The Conclusion on Anticipation  
[330] Neither the abstracts (Maffrand et al entitled “Animal Pharmacology of PCR 4099, A New  
Thienopyridine Compound”, Thebault et al entitled “PCR 4099 – A New Thienopyridine Derivative  
with Potent Anti-Platelet Activity in Man”) nor the ‘875 Patent disclose the invention of the ‘777  
Patent. A POSITA would not be able to come up with the invention of the ‘777 Patent through  
reliance on any of these documents. The Court accordingly finds that the invention of the ‘777  
Patent was not disclosed and was therefore not anticipated.  
D.  
Double Patenting  
[331] On the basis of the principle that there can only be one patent for one invention (Whirlpool,  
above, para 63), Apotex alleges that the ‘777 Patent is invalid upon the basis of double patenting.  
[332] In Whirlpool, above, the Supreme Court of Canada explained the following in connection  
with the prohibition against double patenting, at para 63 :  
[63] It is clear that the prohibition against double patenting involves  
a comparison of the claims rather than the disclosure, because it is  
the claims that define the monopoly.  
[333] In Plavix, the Supreme Court of Canada indicated that although Whirlpool, above, was not a  
selection patent case, the above statement applies to selection patents (SCC Plavix paras 107-108).  
Page: 109  
[334] It was further decided in Plavix that the claims of the ‘777 Patent and the claims of the ‘875  
Patent were not identical or coterminous (SCC Plavix, para 101). The compounds claims in the ‘777  
Patent are distinct from the compounds claimed in the ‘875 Patent.  
[335] No new or convincing evidence has persuaded the Court of Apotex’ allegation that Sanofi  
engaged in double patenting with the ‘875 Patent and the ‘777 Patent. The allegation of double  
patenting is thus rejected by the Court.  
E.  
Utility  
(1) The Lack of Utility  
[336] The lack of utility has been raised by Apotex with respect to the venous thrombosis issue  
which is referred to at page 21 of the ‘777 Patent.  
[337] The Court has already found that the promise of the ‘777 Patent does not guarantee a  
treatment of venous thrombosis. Rather, as concluded earlier by the Court, clopidogrel (the  
compound) can have a use in the treatment of humans. In that context, the issue of whether venous  
thrombosis is a treatment guaranteed by the promise as argued by Apotex is irrelevant.  
[338] In any event, the Court agrees with Sanofi that this issue did not form part of Apotex’  
pleadings. Apotex’ pleadings broadly referred to “humans” but they do not concern any specific  
mention of a lack of utility argument for venous thrombosis.  
Page: 110  
(2) The Demonstrated Utility  
[339] The next issue to be addressed is whether the ‘777 Patent demonstrates utility in humans. In  
this regard, there is evidence that a clopidogrel human study entitled P-1062 was conducted by  
Sanofi for purposes of assessing, among other things, any platelet pharmacological activity. The  
Court shall accordingly consider whether the human study P-1062 demonstrated the utility of the  
‘777 Patent.  
[340] The human study P-1062 report provides summary information. It states that the human  
study P-1062 was a randomized, double-blind study in comparison to placebo with ten (10) healthy  
volunteers.  
[341] As part of the the human study P-1062, each subject was to receive four (4) doses of  
clopidogrel and one (1) dose of placebo with a seven (7)-day interval free of treatment between two  
doses. Phase I studies were mainly conducted to determine the doses for Phase II clinical studies, as  
well as in this case, clinical tolerability and laboratory safety, pharmacological activity (aggregation  
and bleeding), pharmacokinetic profile and drug analysis.  
[342] The human study P-1062 was performed from December 1987 to March 1988. As a result,  
this study was completed after February 1988 – i.e. the date of the filing of the ‘777 Patent. Since  
the human study P-1062 was a double-blind study, the results would not have been available to  
Sanofi or to Sanofi’s inventors until the blind was broken, after the end of the study in March 1988.  
Page: 111  
[343] Dr. Hirsh explained to the Court that in a double-blind study neither the patient – volunteers  
in this case – nor the investigator know whether the placebo or the drug is administered and which  
dose of the drug is administered until the study is completed. Upon completion of the study, the  
blind is broken. When the blind is broken, someone in the statistical department would know  
whether the volunteer received a placebo or the drug. In the event that the volunteer received the  
drug, that person in the statistical department would know the dosage administered. This is called  
the “code” and Dr. Hirsh testified that this “code” would be unknown to the investigators and  
unknown to anyone else – except one or two people in the statistics department – until the study is  
over, the code is broken and the results are presented.  
[344] The evidence adduced at the trial exposed a number of issues and concerns related to the  
human study P-1062.  
[345] Dr. Sanders and Dr. Levy testified that Sanofi would not likely have known the results of the  
study until the blind was broken, i.e. after February 8, 1988. While Dr. Hirsh stated that it was a  
question as to whether the blind study had been broken, Dr. Levy mentioned during the trial that the  
disclosure of parts of the results prior to the completion of the human study P-1062 in March 1988 –  
i.e. after the filing of the ‘777 Patent – may have breached the protocol and might raise concerns as  
to the legality of the process. This would impact whether the results were reliable.  
[346] Further, Dr. Sanders was of the view that even if the results of the clopidogrel study in  
humans completed after February 8, 1988 were known to Sanofi by February 8, 1988, the only  
conclusion that could be drawn was that both compounds were non-toxic at therapeutic doses. There  
Page: 112  
was no demonstration that the toxicity of clopidogrel in humans was superior (had a better toxicity  
profile) to the toxicity of PCR 4099 in humans.  
[347] The Court also observes that Dr. Maffrand confirmed that the studies were conducted on  
healthy volunteers as opposed to patients. In that regard, Dr. Levy was of the opinion that the results  
obtained by Sanofi could not be conclusive. The human study P-1062 had been done mostly on  
healthy subjects and only on very few patients. Hence, for Dr. Levy, Sanofi lacked information and  
it was too early in the process to draw any conclusions that would demonstrate utility and the  
promise of the patent. Dr. Shebuski, an expert for Sanofi, also testified that the data collected by  
Sanofi beginning in February 1988 might not have been sufficient to draw conclusions with respect  
to clopidogrel and its activity on humans (Shebuski, T5125-5126):  
Q.  
In 134, based upon the work you reviewed, what can you say about  
activity in humans? Had that been established?  
No.  
By February 8, 1988?  
No.  
A.  
Q.  
A.  
Q.  
A.  
What more work would have to be done?  
Sanofi was aware of some preliminary data that had been generated  
prior to February 8, 1988. To continue that development, obviously  
they would need to expand that data set in humans.  
The expanded data set, why would that be required?  
That would be required to gain approval of the drug, demonstrating  
safety and efficacy with FDA or other regulatory bodies in the EU.  
Q.  
A.  
[348] On the basis of the evidence and the testimony of the expert witnesses – Dr. Levy, Dr.  
Shebuski, Dr. Hirsh – and the testimony of Dr. Maffrand (fact witness), the Court draws the  
following conclusions:  
!
!
the human study P-1062, a double-blind study was started in  
December 1987 and ended in March 1988;  
the study was performed mostly on healthy volunteers;  
Page: 113  
!
!
some of the results were known by Sanofi prior to the end of the  
double-blind study and at the time of the filing of the ‘777 Patent  
(February 8, 1988);  
the evidence is unclear and a doubt remains as to whether the  
results obtained by Sanofi in January and February of 1988 -  
prior to the end of the study in March 1988 - breached the  
double-blind study protocol; and  
!
in any event, the expert evidence demonstrates that the early  
results of the studies obtained by Sanofi did not provide  
sufficient information to be conclusive.  
[349] For all of these reasons, the Court remains unconvinced that the human study P-1062  
demonstrated the utility of the ‘777 Patent.  
[350] The other issue relevant to the demonstrated utility pertains to Dr. Fréhel (a co-inventor of  
the ‘777 Patent with Mr. Badorc). This issue is the following: Was Dr. Fréhel informed of the  
activity in humans before the filing of the ‘777 Patent? Although the Court has already concluded  
that this issue is not determinative of whether there was demonstrated utility at the time that the  
patent was filed, this issue was nonetheless the subject of much argument and will be addressed by  
the Court, particularly in light of the memo related to the January 28, 1988 meeting.  
[351] Sanofi argued that Dr. Fréhel was informed of the activity in humans and was thus involved  
in the decision-making process. In closing arguments, Sanofi alleged that (i) the results of the  
human study P-1062 were discussed at a meeting held on January 28, 1988, (ii) the minutes of that  
meeting demonstrate that Dr. Fréhel was present at that meeting as an invitee, (iii) some results were  
obtained on the human study P-1062 and, while the study was not yet completed and had not fully  
been analyzed, Sanofi’s view is that inhibition of platelet activation in humans was known and was  
demonstrated prior to the relevant date, i.e. February 8, 1988.  
Page: 114  
[352] Dr. Fréhel did not testify at trial. Mr. Badorc did not assert any knowledge of the results of  
the human study P-1062 prior to February 8, 1988. While Dr. Maffrand gave evidence to the effect  
that Dr. Fréhel was involved in the strategy and was informed of the study (human clinical results),  
a closer look at the documentary evidence raises serious doubts on the participation and  
involvement of Dr. Fréhel in a relevant portion of the January 28, 1988 meeting.  
[353] More particularly, exhibit D-194, Tab 138, confirms that Dr. Fréhel received the memo  
related to the January 28, 1988 meeting. Exhibit D-194, Tab 139, relates specifically to the setting  
up of the January 28 meeting. On the second page there is a list of the invitees for the January 28,  
1988 meeting. There were in fact two parts to the January 28, 1988 meeting. The first part of the  
meeting, meeting A, was held in the morning and related to the mode of action of thienopyridines.  
The other part of the meeting, meeting B, was held in the afternoon and related to the strategy for  
phases 2 and 3 of clopidogrel. The names of the participants in the morning meeting appear on List  
A. The names of the participants attending the afternoon meeting appear on List B.  
[354] However, Dr. Fréhel’s name does not appear on List B. According to the document, Dr.  
Fréhel was not an invitee to the afternoon meeting. It therefore appears that, according to the  
documentary evidence, Dr. Fréhel was not involved in the relevant afternoon meeting where the  
strategy for phases 2 and 3 of clopidogrel was discussed.  
[355] The Court accordingly cannot conclude with certainty that Dr. Fréhel participated in the  
afternoon meeting held on January 28, 1988, and that he was therefore privy to the information  
regarding the activity in humans.  
Page: 115  
[356] For this reason, the Court reiterates that it has not been persuaded that the utility in humans  
has been demonstrated.  
[357] The next step for the Court is to analyze whether the promise for use in humans was soundly  
predicted (Wellcome, below, Olanzapine).  
(3) The Utility – Sound Prediction  
(a) The Promise of the ‘777 Patent  
[358] As the Court has found that the utility of the patent was not demonstrated as of the filing  
date of the ‘777 Patent, the Court must now turn to the issue of whether, as of the filing date, Sanofi  
had a sound prediction for the invention in the ‘777 Patent.  
[359] In Olanzapine, the Federal Court of Appeal stated that “the promise of the patent is  
fundamental to the utility analysis” (para 93). In the case at bar, the Court has already found in that  
there was an explicit promise for use of the compound in humans.  
[360] As such, the utility of the Patent will be measured against that promise (Olanzapine, para  
76).  
[361] The relevant date for sound prediction is the filing date. In this case, the relevant date is  
February 8, 1988.  
Page: 116  
[362] The Supreme Court of Canada in Apotex Inc . et al v Wellcome Foundation Ltd, 2002 SCC  
77, [2002] 4 SCR 153, explained that the doctrine of sound prediction encompasses three (3)  
components. In order to have a sound prediction, there must be: (i) a factual basis, (ii) a sound line  
of reasoning, and (iii) proper disclosure.  
(b) The Prediction  
(i) What is the Utility?  
[363] Sanofi argued that the conditions of a selection patent, such as the ‘777 Patent, apply  
differently to utility compared with novelty, obviousness and double patenting. More particularly,  
during final arguments at trial, counsel for Sanofi appeared to infer that the Federal Court of Appeal  
in Olanzapine distinguished utility from the other invalidity allegations in the context of a selection  
patent. Further, Sanofi argued that the “advantages” of a selection Patent do not apply to the utility  
analysis. For the purpose of recalling what the Federal Court of Appeal held in Olanzapine, the  
Court sets forth the pertinent paragraphs below:  
[27] …[t]he conditions for a valid selection patent serve to  
characterize the patent and accordingly inform the analysis for the  
grounds of validity set out in the Act – novelty, obviousness,  
sufficiency and utility. …  
[28] …It only stands to reason that in undertaking an analysis of  
novelty, obviousness, sufficiency and utility, one should know the  
nature of the beast with which one is dealing.  
[31] …Rothstein J. incorporated his inquiry regarding the alleged  
advantages of clopidogrel bilsulfate (Plavix) into his analyses of  
anticipation, obviousness and double patenting. …  
[32] …Of course, as stated by Lilly, obviousness is relevant to the  
validity of a selection patent and, as Novopharm asserted, so is  
utility. The notion of selection permeates the entire analysis in  
relation to each of the grounds of alleged invalidity.  
Page: 117  
[56] …The invention must be self-evident from the prior art and  
common general knowledge in order to satisfy the "obvious to try"  
test.  
[145] In the context of a selection patent, the obviousness  
analysis considers the species properties of the compound,  
along with its alleged advantages, as described in the  
selection patent disclosure, for it is there that the  
inventiveness of the selection lies.  
…
[75] To establish lack of utility, the alleged infringer must  
demonstrate “that the invention will not work, either in the sense that  
it will not operate at all or, more broadly, that it will not do what the  
specification promises that it will do” …  
[76] However, where the specification sets out an explicit  
“promise”, utility will be measured against that promise” …  
[78] With respect to selection patents, the inventiveness lies in the  
making of the selected compound, coupled with its advantage or  
advantages, over the genus patent. The selection patent must do  
more, in the sense of providing an advantage or avoiding a  
disadvantage, than the genus patent. The advantage or the nature of  
the characteristic possessed by the selection must be stated in the  
specification in clear terms (Sanofi, para. 114). In other words, the  
selection patent must promise an advantage in the sense that, if the  
advantage is not promised, the patentee will not be able to rely on the  
advantage to support the patent’s validity.  
[81] Ultimately, for the purpose of utility regarding a selection  
patent, the question to be determined is whether, as of the date of  
filing, the patentee had sufficient information upon which to base the  
promise. …  
[87] The above-noted inquiries (promise of the patent, information  
upon which to base the promise and information to soundly predict  
the promise) are discrete inquiries. Each requires a separate analysis.  
[88] …It reiterated its position that the advantages are relevant to  
obviousness and have no bearing on whether olanzapine meets the  
utility criteria. …  
[90] …I do not accept Lilly’s position that the advantages are  
relevant only to obviousness. …  
Page: 118  
[93] I have stated earlier that the promise of the patent is to be  
ascertained at the outset of analysis with respect to utility. The  
promise is to be construed by the trial judge within the context of the  
patent as a whole, through the eyes of the POSITA in relation to the  
science and information available at the time of filing. The promise  
of the patent is fundamental to the utility analysis.  
[364] Based on the above-quoted paragraphs from the Federal Court of Appeal’s reasoning in  
Olanzapine, it is clear that the advantages of a selection patent are relevant to the entire inquiry of  
patent validity – obviousness, novelty, utility and sufficiency.  
[365] In addition, for the ‘777 selection Patent, the promise of the patent is the utility for which the  
patent must be measured. As stated by the Federal Court of Appeal in Olanzapine at para 87:  
“The above-noted inquiries (promise of the patent, information upon  
which to base the promise and information to soundly predict the  
promise) are discrete inquiries. Each requires a separate analysis.”  
[Emphasis added]  
[366] With the above in mind, the Court will now turn to the promise of the patent and how it is  
applied to the analysis on sound prediction.  
(ii) The Promise of the Patent  
[367] The promise as construed by the Court is for the use of the invention in humans.  
[368] As the invention encompasses a number of advantages, the manner in which the advantages  
relate to the promise of the patent was a pivotal issue in this case. Hence, the following question:  
Does the Court consider all of the advantages as a whole in the sound prediction analysis, or does  
Page: 119  
the Court consider each of the advantages separately when determining whether the inventor had a  
proper basis for a sound prediction for the promise of the patent?  
[369] Apotex argues that each of the advantages must be individually scrutinized for purposes of  
determining whether there was a sound prediction (i.e. the prediction that it was less toxic and more  
active in humans).  
[370] Yet the Federal Court of Appeal in Olanzapine, at paras 105-106 and 110-112, cautioned  
against separately analyzing each specific advantage to the level of the promise of the patent.  
Apotex’ contention to the contrary must accordingly be rejected.  
[371] More generally, the issue of the promise of the patent is inextricably linked to Apotex’  
argument regarding the relative activity and toxicity of clopidogrel. Thus, the Court turns to this  
next question: How are the advantages of a selection Patent linked to the promise of the Patent?  
Advantages vs Promise of the Patent  
[372] Apotex contends that the promise of the ‘777 Patent was for the relative activity and toxicity  
of clopidogrel in humans. As indicated above, the Court does not consider that each of the  
advantages of the invention is to be assessed independently but Apotex argues that the ‘777 Patent  
promised that each advantage would be substantial. For the reasons stated below, the Court is of the  
opinion that the ‘777 Patent does not promise relative activity, toxicity and tolerability compared to  
the l-clopidogrel or PCR 4099. Rather, the patent only promises that there is a difference.  
Page: 120  
[373] First, one of Apotex’ main arguments is that there is no factual basis or sound line of  
reasoning for the prediction that clopidogrel was less toxic/better tolerated in humans than PCR  
4099 or l-clopidogrel as of February 8, 1988. Apotex refers to Table IV in the ‘777 Patent in this  
regard. Apotex contends that Table IV shows that the LD50 for the racemate PCR 4099 was 1615,  
for clopidogrel bisulfate it was 2591, and for the levo-rotatory it was 1702. The range is from  
highest to lowest calculated at 1.6 and amounts to a range that provides only a slight difference.  
According to Apotex, a skilled person, based on what is in the patent, would have no reasonable  
basis of predicting the difference in toxicity between the compounds.  
[374] Second, Apotex makes a similar argument with respect to relative activity. For Apotex, the  
promise is not merely about activity but rather relative activity. This promise is that clopidogrel is at  
least as active as the racemate PCR 4099, and that the levo-rotatory is inactive or almost inactive.  
Apotex contends that the promise of the ‘777 Patent deals with therapeutic administration of the  
medicine to treat. It follows, according to Apotex, that this is where the promise of comparative  
activity has to be determined.  
[375] Having considered the two (2) arguments above, the Court is of the view that Apotex misses  
the point. Indeed each advantage described in the ‘777 Patent is not to be scrutinized on its own, but  
rather in conjunction with the entire invention as described in the ‘777 Patent.  
[376] In reality, Apotex is asking the Court to reach the very conclusion against which the Federal  
Court of Appeal warned in the Olanzapine decision. The point is that there is one invention and one  
promise of the patent in the case of the ‘777 Patent, and the Federal Court of Appeal accordingly  
Page: 121  
cautioned against separately analyzing each specific advantage referred to in the patent’s disclosure.  
Otherwise, each advantage would be required to reach the level of a promise of the patent. The  
Federal Court of Appeal indicated that this approach amounted to “putting the cart before the horse”  
(para 105).  
[377] The Federal Court of Appeal explained in Olanzapine, at para 106, the following:  
[106] Also of concern in relation to the analysis of each specific  
advantage is whether the trial judge had an appreciation of the  
distinction between the promised advantage (if the specific  
advantage was indeed promised) and the data upon which it is based.  
Ranbaxy addresses this distinction and has been referred to earlier.  
Finally, the approach taken, in the manner in which it was taken,  
precludes the possibility that any number of seemingly less  
significant advantages (when considered separately) may suffice  
when considered cumulatively, provided that the cumulative  
advantage is substantial.  
[378] If Apotex’ line of reasoning were followed, each one of the advantages would not hold up to  
the standard, and thus there would be no sound prediction.  
[379] In particular, if the Court accepted Apotex’ argument regarding the method of relative  
activity, the Court would have to ignore the fact that when the seemingly less significant advantages  
are considered cumulatively, as in the ‘777 Patent, there is a substantial advantage.  
[380] Likewise, Apotex argues that the ‘777 Patent promised a substantial difference between the  
activity, toxicity and tolerability of clopidogrel when compared with l-clopidogrel or PCR 4099.  
Page: 122  
[381] In this regard, the Court recalls that the promise of the patent, as determined earlier in these  
reasons, can be described as the use of the invention in humans. And also as explained earlier, the  
invention of the ‘777 Patent is a compound which is useful in inhibiting platelet aggregation, has  
greater therapeutic effects and less toxicity than the other compounds of the ‘875 Patent, has the  
advantages of the salts (crystallizes easily, not hygroscopic and sufficiently water-soluble) and the  
methods for obtaining that compound.  
[382] As the promise of the patent is the use of the invention for treatment in humans, and the  
invention only specifies “greater” or “lesser” values, the Court will not scrutinize the degree of  
difference as argued by Apotex, but it will inquire into whether there was a sound prediction that  
there would be some degree of activity, tolerability and toxicity difference that would occur in  
humans.  
[383] This is similar to the situation in Servier, above, where Justice Snider found that the promise  
of the ‘196 Patent was that all of the compounds claimed would have some level of inhibition.  
Justice Snider stated at paras 358-359:  
[358] To reiterate my earlier finding, the promise of the ‘196 Patent  
was that all of the compounds claimed would have some level of ACE  
inhibition when measured in vitro and that some of the compounds  
would have sufficient activity to treat hypertension and cardiac  
insufficiency. There was no prediction or promise that all of the  
compounds of claims 1, 2 and 3 would be capable of treating  
hypertension or cardiac insufficiency. It follows that there was no  
prediction that any of the compounds with an all R-configuration on  
the backbone would necessarily be capable of treating hypertension or  
cardiac insufficiency.  
[359] While admittedly demonstrating that compounds with the R-  
configuration had a low level of activity as compared to those with the  
S-configuration, the conclusion I draw from the prior art relied on by  
Page: 123  
Apotex is that compounds with the R-configuration at various  
positions of the backbone would be expected to have some level of  
ACE inhibition. Indeed, this was not disputed by Apotex's experts,  
Drs. Marshall, McClelland, and Thorsett, who agreed that some  
activity was recorded in the prior art when stereoisomers with the R-  
configuration had been used. For example, in his affidavit, Dr.  
Thorsett writes:  
By the filing date of the ‘093 Application... it had been  
established as part of the common knowledge of the person  
skilled in the art that certain stereochemical configurations at  
centers 1-3... namely one or more of them being “R” was  
readily associated with an extremely poor and non-useful  
inhibitor activity against ACE in vitro.  
[Emphasis added]  
[384] Thus, the Court will now turn to the factual basis for asserting the activity, tolerability and  
toxicity differences in animal models. This is the foundation for the prediction that it would have  
use in humans.  
i.  
Information to Base Toxicity and Tolerability Advantages  
[385] The ‘777 Patent contains LD50 results in Table IV. These results are a measure of toxicity  
and tolerability. Sanofi points out that the results contained in Table IV not only demonstrated a  
differential LD50 and LD10 between clopidogrel and the levo-rotatory enantiomer, but also that there  
were convulsions observed with the levo-rotatory enantiomer. The LD50 value is a measure of  
lethality in the test species after a single administration of the compound.  
[386] On this point, Apotex relies on Dr. Sanders’ opinion and contends that the LD50 test was  
conducted in female rats and that it is “obsolete”, “toxicologically inadequate, and misleading”,  
would have “no place in modern pharmaceutical and chemical research” and would not be at all  
predictive of a low repeated dose of toxicity in humans. Thus it would not provide the skilled reader  
Page: 124  
with information about the toxicity that would be expected on administration in the course of  
treatments of the same compounds to humans. Apotex further argues that the skilled person could  
not make a prediction regarding the relative toxicity of clopidogrel, PCR 4099 and I-clopidogrel.  
Finally, Apotex also disputes that clopidogrel has a larger therapeutic index than PCR 4099.  
[387] On this issue, the Court heard from two (2) toxicology experts: Dr. Sanders and Dr.  
Rodricks.  
[388] While the Court favoured Dr. Sanders’ objective background on toxicology, the Court  
recalls that the testimony of both Dr. Sanders and Dr. Rodricks revealed a number of discrepancies.  
[389] Dr. Sanders admitted in cross-examination to having referred to the number 1550 when the  
correct number was in fact 155. Furthermore, with respect to production 234, Dr. Sanders referred  
to the LD as being 1,250 to 5,000 instead of 1,250 to 2,500. The Court does not accept that these  
differences were insignificant and the Court views these mistakes as more than mere typographical  
errors. Although the Court is aware that Sanofi translated these reports with the numbers relied on  
by Dr. Sanders, the fact is that Dr. Sanders relied on incorrect numbers for his opinion. In these  
circumstances, the reliability of Dr. Sanders’ report and testimony were questionable.  
[390] Similarly, Dr. Rodricks claimed during cross-examination to have performed a given  
calculation but failed to provide it in support of his related conclusions. Also disconcerting to the  
Court was the fact that Dr. Rodricks tendered an expert report in another proceeding, described as  
the Levaquin Report which reviewed a series of preclinical tests on levofloxacin as well as the  
Page: 125  
racemate ofloxacin. During cross-examination, it was revealed that Dr. Rodricks borrowed and  
imported identical paragraphs from the Levaquin Report into his report in the case at bar and hence  
provided selective information to the Court. Again, the reliability of Dr. Rodricks on this issue is  
questionable.  
[391] Thus, whilst the Court found the testimonies of Dr. Rodricks and Dr. Sanders to be of some  
assistance on the issue of toxicity, it has given them limited weight.  
[392] In terms of persuasive evidence given on this point, the Court notes that a Sanofi study (D-  
136, Tab-122 – SA361) demonstrated a differential LD50 and LD10 and that convulsions were a  
problem with PCR 4099 and the levo-rotatory enantiomer but not with clopidogrel. On this basis, it  
can be concluded that there was a differential toxicity as well as the better tolerability of  
clopidogrel.  
[393] The Court also notes that Dr. Sanders testified that a comparative toxicity between two (2)  
compounds could be demonstrated by a two (2)-week repeated dose toxicity study in two (2)  
species. Such a study was in fact conducted by Sanofi.  
[394] In addition, the Court reviewed the numerous previous toxicological studies in different  
species of both sexes (rat, mouse and baboon) prior to February 8, 1988, including:  
(a) acute oral toxicity studies in male and female rats with both  
enantiomers and racemate (SA361, SA234, SA409, SA388,  
SA528);  
(b) acute oral toxicity studies in male and female mice with both  
enantiomers and racemate (SA234, SA409, SA528); based upon  
review of the ‘777 Patent and Sanofi internal reports;  
Page: 126  
(c) one-week dose ranging study in male and female rats with PCR  
4099 (SA236);  
(d) two-week oral toxicity study in male and female rats with  
SR25989C (SA407);  
(e) two-week oral dose range finding study in male and female rats  
with SR25990C (SA404);  
(f) two-week oral toxicity study in male and female baboons with  
SR25989C (SA408);  
(g) two-week oral toxicity in male and female baboons with SR25990C  
(SA526);  
(h) one-year toxicity study in male and female baboons with PCR 4099  
(SA412);  
(i) six-month toxicity study in male and female baboons with PCR  
4099 (SA277);  
(j) four-week oral toxicity in male and female baboons with PCR 4099  
(SA227);  
(k) one-week dose range finding study in male and female baboons  
with PCR 4099 (SA238); and  
(l) numerous other toxicology studies on PCR 4099.  
[395] On the basis of this evidence, the Court finds that Sanofi has demonstrated the differential  
toxicity as well as the better tolerability of clopidogrel.  
ii.  
Information to Base Activity Advantage  
[396] In connection with the tests performed by Sanofi scientists in order to demonstrate the  
activity difference between the D and the L enantiomers in animal models, the Court recalls the  
following comments made by Dr. Hirsh:  
Q. Okay, then it describes:  
“The enantiomers were synthesized and tested in animals in order  
to assess their ex vivo antiplatelet activity and antithrombotic  
activity.”  
[as read]  
That’s consistent with your review of the papers?  
A. Yes, yes.  
Q. Then it says:  
“The L enantiomer has no ex vivo antiplatelet activity in rats.”[as read]  
A. Correct.  
Q. Consistent with what you have seen before?  
Page: 127  
A. Yes.  
Q. “And enantiomer D alone has antiplatelet activity and is therefore  
twice as active as PCR 4099.”[as read]  
A. That’s what it says, yes.  
Q. A little bolder than what the patent said?  
A. Yes.  
Q. But certainly an understanding at the time?  
A. That’s what they said, yes.  
Q. “Enantiomer D alone has antithrombotic properties with dose response in  
rats.”[as read]  
And that would have been based on the various antithrombotic testing  
that had been done?  
A. Right.  
Q. And it says:  
“These results, together with the first results obtained on acute toxicology  
showing that the inactive L enantiomer toxicity was more marked than the  
active enantiomer D, probably even more than the racemic, led us to develop  
active enantiomer, the D enantiomer.”[as read]  
(Hirsh, T688-690)  
[397] Dr. Hirsh further discussed the advantages of the D compared to the L enantiomer and how  
they were identified:  
A. The D has advantages over the L when it comes to activity, yes.  
Q. Yes.  
And how was that advantage identified?  
A. The advantage was identified in three ways. It was identified in the  
aggregation tests. It was identified in the single model of the screw  
in the vena cava, and it was identified in the LD-10, 50, 90 studies.  
(Hirsh, cross T598)  
[398] The Court also observes that the inventors of the ‘777 Patent made it clear that they had  
demonstrated the differential activity in rat model. The ‘777 Patent states:  
!
!
The levo-rotatory isomer is inactive and the dextro-rotatory  
isomer is at least as active as the racemate (page 13).  
The results shown in Table II demonstrate again that only the  
dextro-rotatory isomer is active whereas the salts have  
comparable activities (page 15).  
!
The results which are presented in Table III show that the levo-  
rotatory isomer is inactive in this test, in contrast to the dextro-  
rotatory isomer and the racemate (page 17).  
Page: 128  
[399] Based on the evidence above, the Court accordingly finds that Sanofi has demonstrated the  
differential activity of clopidogrel.  
[400] It follows that Sanofi has established the foundation for the promise of the patent. The Court  
must now determine whether Sanofi has established a prima facie reasonable inference that the  
invention could be used in humans. To this end, the Court must assess whether there was a prima  
facie reasonable inference of utility.  
(iii) Prima Facie Reasonable Inference of Utility  
[401] The Federal Court of Appeal in Olanzapine emphasized that the threshold required to  
support a line of reasoning is “that a sound prediction requires a prima facie reasonable inference of  
utility” (para 112).  
[402] What is a prima facie reasonable inference of utility? The answer is evidence which on its  
face allows it to be reasonable to conclude, based on the facts, that the invention is useful and does  
what the patent says it will do.  
[403] It is thus relevant at this juncture to consider more closely the factual basis underlying the  
sound prediction/utility.  
(c) Factual Basis  
(i) Summary of Chronology  
Page: 129  
[404] The Court will now consider all of the advantages of the invention of the ‘777 Patent as a  
whole and will determine whether there was a factual basis for the prediction that the invention  
could be used in humans.  
[405] The starting point for this analysis is to assess the chronology of events that lead up to the  
discovery of clopidogrel bisulfate and the work that was done at Sanofi before the filing date of the  
‘777 Patent.  
[406] Although there was a substantial amount of evidence presented at trial regarding the “factual  
basis for the prediction”, a few of the studies that were disclosed in the ‘777 Patent stand out as  
critical to the foundation, including:  
!
!
!
!
!
PCR 4099 was a racemate that was active;  
PCR 4099 was toxic in a one (1) year study of baboons;  
L-clopidogrel is inactive in vivo;  
D- clopidogrel is at least as active as the racemate; and  
L-clopidogrel was toxic, but the D was not toxic.  
In vitro – Ex vivo – In vivo  
[407] Before assessing the work on ticlopidine and PCR 4099, it is helpful to recall that platelet  
function and aggregation responses can be monitored in a number of ways that are usually referred  
to as in vitro, ex vivo or in vivo:  
!
!
!
In vitro refers to studying blood platelets from a sample of  
blood, obtained by venipuncture or other means from a human or  
an animal, in a test tube;  
Ex vivo refers to studying blood platelets from a sample of blood  
in which the human or animal subject was previously  
administered an antiplatelet medication; and  
In vivo refers to studying platelet function and resulting  
thrombus formation in a human or an animal model which  
mimics the thrombotic process which occurs in human beings.  
Page: 130  
[408] It is also recalled that the ‘777 Patent describes ex vivo testing and in vivo testing.  
[409] In this case, the Court had the benefit of hearing from Dr. Maffrand, the inventor of the ‘875  
genus Patent as well as from Mr. Badorc, a named inventor of the ‘777 Patent. Both testified on the  
’777 selection Patent. Dr. Maffrand and Mr. Badorc provided insightful testimony regarding the  
history and the work conducted by Sanofi that eventually led to clopidogrel. Also, in their final  
arguments, counsel for Sanofi provided the Court with a very helpful summary of the work  
conducted by Sanofi in the 1970s and 1980s. This background evidence is relevant to the issue of  
sound prediction of utility and is accordingly reviewed next.  
Ticlopidine  
[410] In the early 1970s, Sanofi was conducting research on a class of compounds called  
thienopyridines. Thienopyridines have a two-ring structure consisting of a five (5) membered ring  
containing a sulphur atom fused to a six membered ring containing a nitrogen atom:  
[411] One of the compounds identified during this research was ticlopidine, which was  
synthesized in about July 1972. Ticlopidine has the following formula:  
Page: 131  
[412] Given ticlopidine’s unfavourable side effect profile, there was a need for a drug that was as  
effective or as more effective than ticlopidine, without the risk of rare but potentially fatal blood  
disorders. Therefore, Sanofi continued its research on this class of compounds.  
[413] While hundreds of racemates were made, Sanofi only worked on separating three (3)  
racemates: PCR 1033, PCR 3549 and PCR 4099.  
PCR 1033  
[414] In 1975, the methyl analog of ticlopidine was synthesized, which was referred to as PCR  
1033. PCR 1033 has the following formula:  
[415] PCR 1033 differs in structure from ticlopidine. Thus, unlike ticlopidine, PCR 1033 is a  
racemate.  
Page: 132  
[416] PCR 1033 was tested for antiplatelet aggregation activity and it appeared that PCR 1033  
could be considered as a candidate for development as an antiplatelet aggregation agent. However,  
based on pharmacological studies, the observed toxicity appeared to be worse than that of  
ticlopidine. Therefore, it was concluded that PCR 1033 was not a good candidate for further  
development.  
PCR 3071 and PCR 3072 – The Enantiomers of PCR 1033  
[417] At this point, Dr. Maffrand asked Mr. Badorc to try to obtain the enantiomers of PCR 1033  
to see whether the enantiomers of PCR 1033 would have different properties and whether either  
enantiomer might have a better risk/benefit ratio than PCR 1033.  
[418] In March 1978, using a technique known as diastereomeric salt formation, Mr. Badorc  
separated the enantiomers of PCR 1033.  
[419] However, testing showed that PCR 3071 exhibited antiplatelet activity while PCR 3072 was  
inactive.  
[420] PCR 3071 was never tested in humans. Based upon the results of toxicology testing, PCR  
3071 was tolerated less well than ticlopidine and could not be administered to humans. The decision  
was made to cease development of PCR 3071.  
Page: 133  
PCR 3549  
[421] In 1978, Mr. Badorc synthesized the ethyl analog of ticlopidine, which was called PCR  
3233. PCR 3549 has the following structure:  
[422] PCR 3549 differs from ticlopidine in that it is a chiral thienopyridine compound with an  
ethyl derivative on the bridge carbon. Like PCR 1033, PCR 3549 is a racemate.  
[423] Testing conducted by the biological department showed PCR 3549 to be more active than  
ticlopidine. PCR 3549 was also better tolerated than PCR 1033 but less well tolerated than  
ticlopidine. Based on an apparently favourable activity/toxicity ratio, Dr. Maffrand formed the view  
that PCR 3549 should be developed as a drug candidate.  
[424] In November 1978, Dr. Maffrand asked Mr. Badorc to separate PCR 3549 into its  
enantiomers to see if one of the enantiomers had a better risk/benefit ratio.  
[425] In April 1979, Mr. Badorc was successful in obtaining the enantiomers of PCR 3549 using  
the asymmetric synthesis technique.  
Page: 134  
[426] The two enantiomers were sent to the biological department for testing in July 1979. Testing  
revealed that the enantiomers had platelet aggregation inhibiting activities comparable to the  
racemate PCR 3549 (see page S277091 of Trial Ex. D-148). In light of this information, Dr.  
Maffrand made a decision that the development of the enantiomers ought to be abandoned.  
Dr. Maffrand and his colleagues then focused their efforts on PCR 3549.  
[427] It was found that PCR 3549 lacked sufficient therapeutic activity and thus the development  
of PCR 3549 was abandoned.  
[428] After the work on the compounds described above, Dr. Maffrand and his colleagues  
continued to do research on thienopyridines. Dr. Maffrand explained that the purpose of this  
research was to find a more potent compound with a better risk/benefit ratio than ticlopidine.  
Dr. Maffrand hoped to develop a drug that was at least as effective as ticlopidine, with a lower risk  
of side-effects.  
The ‘875 Genus Patent  
[429] Some of the thienopyridine compounds made by Sanofi fell within a distinct genus that was  
later disclosed in Canadian Patent No. 1,194,875. The general formula in the ‘875 Patent is as  
follows:  
Page: 135  
O
N
Y
C
C H  
*
S
X
[430] From about 1976, Sanofi decided to synthesize representatives of this class of compounds.  
Sanofi had previously tested less complex functional groups, such as in PCR 1033 and PCR 3549.  
Prior to July 13, 1982, Mr. Badorc made at least twenty one (21) of these particular compounds. All  
were racemates.  
[431] In March 1980, Mr. Badorc synthesized the ethyl ester known as PCR 3935.  
[432] Based upon the results provided by the biological department, it appeared that PCR 3935  
demonstrated good platelet aggregation inhibiting activity.  
PCR 4099  
[433] In July 1980, Mr. Badorc synthesized the hydrochloride salt of another thienopyridine  
compound called PCR 4099. The free base of PCR 4099 has the following structure:  
Page: 136  
[434] The only difference between PCR 3935 and PCR 4099 is that the OCH3 group is connected  
to the carbon (marked “C”), as opposed to an OCH2CH3 group.  
[435] Sanofi’s biological department tested PCR 4099 using screening tests, including an  
antiplatelet aggregation test. Based on these internal results, it was found that (i) PCR 4099 was the  
most potent thienopyridine compound synthesized to that point of time; and (ii) it was significantly  
more effective and better tolerated than ticlopidine.  
[436] During that time, PCR 4099 underwent further testing. From about July 1980 until about  
July 1982, seventeen (17) other compounds from the ‘875 genus were synthesized by Mr. Badorc.  
All of these twenty-one (21) compounds were later included as examples in the ‘875 Patent and  
were tested for activity by Sanofi’s biological department.  
Decision to Resolve PCR 4099 into its Individual Enantiomers  
[437] By 1985, Dr. Maffrand was aware that testing had shown that PCR 4099 had potential  
negative side effects. Various toxicology studies conducted in 1983 and 1985 had demonstrated the  
possible tendency of PCR 4099 to cause convulsions in animals at particular dose levels. Further,  
Dr. Maffrand was still preoccupied with the side effects observed with ticlopidine. With the goal of  
finding a compound with a better profile than PCR 4099 (and ticlopidine), Dr. Maffrand decided in  
November 1985 to have the enantiomers of PCR 4099 separated and tested.  
Page: 137  
[438] Therefore, around November 1985, Dr. Maffrand had a conversation with Dr. Daniel Fréhel  
in which he told Dr. Fréhel that he would like Mr. Badorc to attempt to separate the enantiomers of  
PCR 4099.  
[439] Further testing was conducted on the enantiomers of PCR 4099, leading to the discovery of  
clopidogrel bisulfate and the invention of the ‘777 Patent.  
[440] The sequence of events is more fully summarized in Appendix C.  
(ii) Important Events in Factual Basis  
[441] Sanofi had an extensive “track record” that led to the development of clopidogrel bisulfate  
and the ‘777 Patent. This “track record” provided Sanofi with a factual basis for their prediction that  
the invention could be used in humans. It is important to highlight its extensive familiarity with the  
class of compounds leading to the invention, including:  
!
!
the work on ticlopidine;  
the work on PCR 4099;  
(i) the one-year study on baboons  
the work on enantiomers of PCR 4099 – d clopidogrel.  
!
(a)  
Work on Ticlopidine  
[442] As previously mentioned, ticlopidine is part of a class of compounds called thienopyridines.  
Ticlopidine was synthesized in or about July 1972. Ticlopidine (Ticlid®) was introduced in France  
in 1978 and in the U.S. in 1991. However, after ticlopidine was launched in France, it was learned  
that, when administered to humans, potential fatal blood disorders (neutropenia and thrombotic  
thrombocytopenic purpura) were associated with it. A number of deaths had been reported to that  
Page: 138  
effect. Therefore, the work on thienopyridines continued with the objective of finding a drug as  
effective as ticlopidine but without the risk of fatal blood disorders. This led to the work on PCR  
4099.  
(b)  
Work on PCR 4099  
[443] In July 1980, Mr. Badorc synthesized the hydrochloride salt of another thienopyridine  
compound called PCR 4099.  
[444] During the trial, it became clear that Sanofi had invested significant amounts of time, money  
and resources to the development of PCR 4099. The following is a list of studies that were  
performed on PCR 4099 before it was discontinued (Shebuski Report, para 125):  
SA No.  
SA268  
Title of Study  
Tolerance and pharmacological activity of  
single ascending doses  
Date  
Report date: April 19,  
1985  
SA273  
Tolerance and pharmacological activity of  
repeated dose  
SA273 – Report date:  
June 28, 1985  
SA255  
SA267  
SA290  
SA255 – Report date:  
September 1984  
Report date: April 15,  
1985  
SA290 - Report date:  
February 10, 1986  
Tolerance and pharmacological activity of  
repeated dose  
Comparison of PCR 4099 (150 mg/day) with  
Ticlopidine (500 mg/day)  
SA292  
SA297  
SA292 - Report date:  
February 10, 1986  
SA297 - Report date:  
March 14, 1986  
Tolerance and pharmacological activity of  
ascending doses PCR 4099/placebo and  
Ticlopidine  
SA306  
SA327  
SA306 – Report date:  
May 29, 1986  
Ascending dose tolerance and efficacy of PCR Report date:  
4099 in healthy human volunteers September 11, 1986  
Page: 139  
Report date: February  
10, 1986  
Study completed:  
June 1987  
SA291  
SA426  
SA420  
Pharmacological activity of PCR 4099  
Tolerance and pharmacological activity on  
thrombocythemic patients  
Double blind cross-over safety and activity  
study comparing once daily to twice daily  
multiple dose treatment of PCR 4099 in healthy  
volunteers  
Study completed:  
November 1986  
SA387  
SA418  
Tolerance and pharmacological activity on  
haemodialysis patients  
Double blind tolerance and activity study  
comparing placebo with four dose levels of  
PCR 4099 in a patient population with  
peripheral arterial disease  
Report date:  
September 4, 1987  
Study completed:  
May 1987  
SA419  
Tolerance and pharmacological activity of PCR Study completed:  
4099 administered as a single ascending dose  
(50/150/300 mg) to healthy volunteers  
Mechanism of action: study of glycoproteins  
GP IIb/IIIa  
Systemic absorption of radiocarbon labelled  
PCR 4099 after oral intake of a single 150 mg  
dose in healthy volunteers  
July 1986  
SA424  
SA343  
Study completed:  
May 1987  
Report date: January  
23, 1987  
SA429  
SA428  
SA427  
SA430  
SA391  
Interaction 4099 and Cimetidine  
Study completed:  
January 1987  
Influence of food intake on Pharmacokinetics  
of PCR 4099 after a single dose  
Tolerance and pharmacological activity on  
thrombocythemic patients  
Study of PCR 4099 administered with or  
without antacid medication  
Study completed:  
February 1987  
Study completed:  
September 1987  
SA430 - Study  
completed: May 1987  
SA 391 – Report  
date: October 10,  
1987  
SA356  
SA423  
Study of PCR 4099 administered before/after  
coronary by-pass graft (CABG)  
Study of PCR 4099 administered before and  
Report date: March  
20, 1987  
Study completed:  
after coronary artery by-pass graft (CABG) vs. June 1987  
Ticlopidine  
SA421  
SA422  
Pharmacological activity and tolerance of PCR Study completed:  
4099 in arteritic patients vs. Ticlopidine  
Pharmacological activity of PCR 4099  
compared with ticlopidine in arteritic patients  
September 1987  
Study completed:  
July 1987  
Page: 140  
[445] The Court also notes that Dr. Lacheretz took part in and authored numerous studies  
regarding PCR 4099.  
[446] Based on the results yielded by these internal studies, it was found that (i) PCR 4099 was the  
most potent thienopyridine compound synthesized to that point of time, and, (ii) it was significantly  
more effective and better tolerated than ticlopidine.  
[447] While Mr. Badorc was working on separating the enantiomers of PCR 4099, important work  
was conducted on PCR 4099. This work included pre-clinical and clinical work and is summarized  
in the investigational brochure PCR 4099 – An Antithrombotic Agent (Trial Ex. D – 135, Tab 73(a)  
(SA305). A number of studies using PCR 4099 were performed. The most important and  
compelling study was the one-year study conducted by Sanofi’s toxicology department.  
[448] More particularly, a one-year study on baboons produced effects that cannot necessarily be  
observed with short-term studies, such as a three-month study, and PCR 4099 showed promising  
potential to be used as a clinical drug.  
[449] The one-year toxicity study on baboons started in April 1986 and ended in June 1987. This  
study was conducted at a low dose of 25, 100 and 400 mg/kg of PCR 4099. In parallel, Sanofi  
continued to observe convulsions, and the convulsions reached their pinnacle in the one-year  
toxicity study on baboons (SA412). These studies taken as whole unquestionably demonstrated that  
convulsions were present and Sanofi concluded that they were due to the toxicity of PCR 4099.  
Page: 141  
[450] The Court notes that the breadth of experience that Sanofi had regarding the types of short  
and long-term studies with PCR 4099 added to the factual basis for prediction. The pivotal evidence  
in this regard was provided by Dr. Lacheretz.  
[451] Dr. Lacheretz testified that he was personally and directly involved in numerous studies with  
PCR 4099, including the one (1)-year study on baboons. At the time of the one (1)-year study, Dr.  
Lacheretz was working at Sanofi. He left Sanofi the following year. Dr. Lacheretz explained the  
following:  
[…] Bien cette page 17 regroupe les observations quotidiennes, la  
synthèse des observations quotidiennes réalisée pendant cette étude qui a  
duré un an. Et ces observations ont révélé l’apparition de crises  
convulsives dans les trois groupes traités. Encore une fois, on utilise trois  
niveaux de dose et dans les trois doses utilisées, on a observé des crises  
convulsives.  
[…]  
[…] Au terme de ce programme toxicologique réalisé avec PCR 4099, on  
constate factuellement que des convulsions sont systématiquement  
observées et qu'avec la chronicité du traitement, un effet dose est  
clairement observé également, ce qui conduit à pouvoir imputer ces  
convulsions directement au produit. Donc l'ensemble du programme est  
allé vers la confirmation de l'imputabilité de ces convulsions au produit.  
(Lacheretz, T3688-3689)  
Page 17 re-groups the daily observations. Some of these are over the one  
year of the study and these observations indicated a pattern of convulsive  
crisis in three groups. We have three levels of dosage and in the three  
doses used there were convulsive crisis.  
...  
At the end of this toxicology program for PCR 4099 we observed that  
convulsions were systematically observed and with the treatment the  
dosage effect is clearly observed which leads one to be able to impute  
Page: 142  
these convulsions to the product. So the overall program did confirm the  
responsibility of the product.  
(Lacheretz, English RD7530)  
[452] Based on Dr. Lacheretz’ testimony, it is clear that Sanofi concluded that the convulsions  
were dose-dependent.  
[453] As for the testimony provided by the toxicology experts, they both revealed flaws. However,  
on the issue of the one-year study on baboons, the Court prefers Dr. Rodricks’ testimony because it  
confirms and complements Dr. Lacheretz’ testimony. In particular, Dr. Rodricks explained that the  
baboons could not tolerate the very high doses that were used in shorter term studies. They  
succumbed early. Dr. Rodricks further explained that the point behind the longer one-year study  
was to get the material into the animals at a dose that would not cause them to die early or to  
otherwise be disabled, considering that a one-year study at a lower dose could produce effects that  
would not necessarily be observed with short-term studies e.g. three (3) months. On that point, in  
cross-examination, Dr. Sanders testified to the same effect regarding lower dosage.  
[454] The results concerning the one-year study in baboons are in a table on which Dr. Rodricks  
provided the following explanation:  
First of all, you see on the left, they have three different groups of  
baboons. Then you see in the second column the doses used for each  
group. So there is a 0, that’s the control, 25, 100 and 400, and then the  
number of animals presenting with seizures.  
So a number of animals in which they saw it, and then they also have  
the number of seizures. Some animals had more than one seizure  
during the study. And the importance of the table, we have a general  
conclusion about convulsions, but what this table tells me as a  
toxicologist is that you had an increasing rate of convulsions, more of  
them, as the dose went on.  
Page: 143  
(Rodricks, T3308-3311)  
[455] Dr. Rodricks further opined that the dose-dependent response illustrated by the one-year  
study indicated that the convulsions were a result of the compound and not a result of the proneness  
of baboons to convulsions.  
[456] In this regard, Apotex argues that the convulsions in baboons at 25 milligrams per kilogram  
would not be considered important because the baboons were prone to convulsions, and were not  
considered to be a good model for what would occur in humans in this respect. However, Dr.  
Lacheretz explained why the baboon was chosen for the studies:  
Le babouin, je le précisais précédemment, l’espèce non rongeur, on a le  
choix entre le chien, c’est souvent le chien qui est utilisé, le primate non  
humain, et à l’époque on utilisait des babouins pour des raisons sanitaires  
et politiques – aujourd’hui, on utilise du macaque –, et la troisième espèce  
non rongeur qui était possible était le micro porc.  
Et généralement, en première intention, le chien était sélectionné. Ce  
que je me souviens de cette époque, c’est que pour le développement  
de ticlopidine et pour des dérivés de thiénopyridine, ces produits  
induisaient des vomissements chez le chien, à des doses assez  
faibles, ce qui ne rendait pas possible la réalisation des études  
toxicologiques chez le chien. Il est connu que le chien peut présenter  
des vomissements assez facilement, un chien peut vomir facilement  
sans que ce soit d'origine pathologique, et donc c'est parfois une  
limitation à l'utilisation du chien dans les études de toxicologie. Et  
l’alternative à cette difficulté est de sélectionner le primate non  
humain. C’est la raison pour laquelle ces études du PCR 4099 ont  
conduit à la sélection du babouin.  
(Lacheretz, T3682-3683)  
Well, as I specified earlier, non-rodent species over the choice between the  
dog -- and often dogs are used. The non-human primate, at the time we  
used baboons for sanitary and political reasons. This is no longer the case  
Page: 144  
today. We use (foreign word). And the third non-rodent species which was  
possible was a mini-pig. And usually the dog was chosen first.  
What I remember of this time is that for development of ticlopidine and  
thienopyridine the product induces the vomiting in dogs at fairly low doses  
which made it impossible to carry out toxicology studies in dogs. It’s a  
known fact that dogs vomit fairly easily. A dog can vomit easily without it  
being because of pathology so this sometimes placed a limit on the use of  
dogs in toxicology studies. The alternative to this difficulty is to select the  
non-human primates and that's why PCR 4099 studies led to the selection  
of a baboons.  
(Lacheretz, English RD7530)  
[457] Dr. Lacheretz’ testimony unquestionably confirms in the Court’s view that the baboon was  
the most appropriate animal model for the prediction in humans. Based on their previous experience  
with the dog model in a similar compound, it was the logical choice to use the baboon for study  
purposes.  
[458] Finally, as a result of the one-year study on baboons, Sanofi decided to stop the work on  
PCR 4099 in April 1987. Significantly, the “Simon Memo” dated April 16, 1987, sent by Mr. Pierre  
Simon, Director of Research and Development at Sanofi Research, stated that the studies conducted  
on PCR 4099 would cease allegedly due to convulsions. The Court ruled during trial that this memo  
was a proper business record under s 30(1) of the Canada Evidence Act but that it was cognizant  
that the memo represents Dr. Simon’s beliefs. It was at this point that Sanofi focused their attention  
on the enantiomers of PCR 4099.  
(c)  
Work on Enantiomers of PCR 4099  
(i) The ‘777 Patent: ex vivo Studies  
Page: 145  
[459] The Court recalls that three (3) tests were performed and the resulting data is reflected in  
four (4) tables in the ‘777 Patent.  
[460] The first test is an ex vivo test wherein the activity on the aggregation of platelets was  
induced by ADP or collagen and then measured by using the well-established Born method. The  
Court notes the following:  
! Tables I (page 14) and II (page 16) of the ‘777 Patent set out  
the results of the platelet aggregation assays using ADP and  
collagen, respectively.  
! The results shown in Table II demonstrate again that only the  
dextro-rotatory isomer is active whereas the salts have  
comparable activities.  
! The antithrombotic activity of the compounds was studied in  
a venous thrombosis test using a screw thread described by T.  
Kumada et al “Experimental model of venous thrombosis in  
rats and effect of some agents” (1980) Thrombosis Research  
18; 189-203, Exhibit 8. Based on this testing, the ‘777 Patent  
concludes on page 17 that the levo-rotatory isomer is inactive  
in this test, in contrast to the dextro-rotatory isomer and the  
racemate.  
(ii) Additional ex vivo Studies  
[461] In addition to the ex vivo assays set out in the ‘777 Patent, Sanofi also conducted additional  
ex vivo assays which are summarized and explained in Dr. Shebuski’s report at para 86 and  
following:  
a. The ex vivo kinetic effect of SR 25990C on ADP-induced  
platelet aggregation was studied in female rats (n=5)  
administered SR 25990C at oral doses of 2.5 and 10 mg/kg  
(SA414, page 8; SA111, pages S05135-S05148). SR 25990C  
was only modestly effective at the low dose (2.5 mg/kg) whereas  
at the higher dose (10 mg/kg), SR 25990C started to show an  
impairment of platelet aggregation at 0.5 hr post oral  
administration with the maximal effect occurring at around 6 hrs  
post-treatment. By 72 hrs, the platelet aggregation responses had  
still not returned to the baseline control responses.  
Page: 146  
b. Similarly, the ex vivo kinetic effect of SR 25990C on collagen-  
induced platelet aggregation velocity was studied in female rats  
(n=5) administered SR 25990C at oral doses of 2.5 and 10  
mg/kg (SA414, page 9; SA111, pages S05135-S05148). SR  
25990C was only modestly effective at the low dose (2.5 mg/kg)  
whereas at the higher dose (10 mg/kg), SR 25990C started to  
show an impairment of platelet aggregation velocity at 0.5 hr  
post oral administration with the maximal effect occurring at  
around 6 hrs post-treatment. By 72 hrs, the platelet aggregation  
responses had still not returned to the baseline control responses  
owing to the irreversible nature of this inhibitor.  
c. The ex vivo effect of SR 25990C on ADP-induced platelet  
aggregation was evaluated at 2 hrs post-administration of SR  
25990C orally at single doses of 1.25, 2.5, 5.0 or 10 mg/kg in  
male and female rats (n=5 each). Ticlopidine was also evaluated  
at a dose of 100 mg/kg, p.o. (SA414, page 10; SA110, pages  
S05035-S05052; SA111, pages S05089-S05095). The 2.5 mg/kg  
dose of SR 25990C was modestly effective with the most  
inhibition (approx. 75% or greater) observed at the 10 mg/kg  
dose in females and 20mg/kg in males. Ticlopidine, at the 100  
mg/kg dose, was relatively ineffective, at the dose administered  
in this test, compared to SR 25990C.  
d. Similarly, the ex vivo effect of SR 25990C on collagen-induced  
platelet aggregation velocity was evaluated at 2 hrs post-  
administration of SR 25990C orally at single doses of 1.25, 2.5,  
5.0 or 10 mg/kg in female rats and 2.5, 5, 10 and 20 mg/kg in  
male rats (n=5 each). Ticlopidine was also evaluated at a dose of  
100 mg/kg, p.o. (SA414, page 11; SA110, pages S05035-  
S05052; SA111, pages S05089-S05095). The 2.5 mg/kg dose of  
SR 25990C was modestly effective with the most inhibition  
(approx. 75% or greater) observed at the 10 mg/kg dose in  
female rats. In male rats, the 20 mg/kg dose of SR 25990C was  
more inhibitory than the 10 mg/kg dose. Male rats appeared to  
require a slightly higher dose of SR 25990C than female rats to  
attenuate collagen-induced platelet aggregation velocity to a  
similar degree. Ticlopidine, at the 100 mg/kg dose, was  
relatively ineffective, at the dose administered in this test,  
compared to SR 25990C in both female and male rats.  
e. The ex vivo effect of SR 25990C on thrombin-induced platelet  
aggregation was also evaluated at single oral doses of 1.25, 2.5,  
5 and 10 mg/kg in female rats (n=5) and 2.5, 5, 10 and 20 mg/kg  
in male rats (n=5). Ticlopidine was also evaluated at a dose of  
Page: 147  
100 mg/kg, p.o. (SA414, page 12; SA111, pages S05098-  
S05102; SA131 pages S05218-S05220) to female and male rats  
(n=5 each). The 5 mg/kg dose of SR 25990C was highly  
effective against thrombin-induced platelet aggregation with the  
most inhibition (approx. 90% or greater) observed at the 10  
mg/kg dose in female rats. In male rats, the 20 mg/kg dose of SR  
25990C was similarly effective to the 10 mg/kg dose in female  
rats. Ticlopidine, at the 100 mg/kg dose, was relatively  
ineffective, at the dose administered in this test, compared to SR  
25990C in both female and male rats.  
f. The effectiveness of single oral doses of SR 25990C on ADP-  
induced ex vivo platelet aggregation in rats (n=5) was evaluated  
when the compound was administered either p.o. or  
intraduodenal (i.d.) in doses of 2.5, 5 and 10 mg/kg (SA414,  
page 13; SA111, pages S05123-S05126, S05167-S05168). The  
intraduodenal route, at all doses studied, was more effective than  
the p.o. dosing regimen to attenuate ADP-induced platelet  
aggregation.  
g. Biliary and pancreatic secretions, in the antiaggregatory (ADP)  
effect of SR 25990C after intraduodenal administration, were  
evaluated in rats (SA414, pages 14-15; SA137, pages S057539-  
S057555). Animals treated with SR 25990C with a biliary shunt  
had profoundly more inhibition of ADP-induced platelet  
aggregation compared to those animals with a water shunt.  
h. The effect of SR 25990C on ex vivo ADP-induced platelet  
aggregation was studied in rats following 4 different routes of  
administration; p.o., i.v., i.p., and i.d. (SA414, page 16; SA110,  
pages S05035-S05052; SA111, pages S05161-S05166; SA111,  
pages S05131-S05134). Doses of SR 25990C ranged from 1.25  
to 100 mg/kg. At a dose of SR 25990C of 5 mg/kg, p.o., ADP-  
induced aggregation was attenuated by approx. 60% or greater  
with profound inhibition at 10 mg/kg, p.o. Administration of SR  
25990C by the i.v. route, inhibited ADP-induced aggregation as  
well but to a slightly lesser extent at comparable doses to the p.o.  
route. Dosing of SR 25990C by the i.p. route was effective at 10  
mg/kg and the s.c. route was highly ineffective, even in doses up  
to 100 mg/kg, indicating greater bioavailability following i.d. vs.  
p.o. routes of administration. However, intraduodenal dosing is  
not a normal means of drug administration applicable to  
therapeutic drug commercialization.  
i. Evaluation of the onset of action of SR 25990C in rats after oral  
or intravenous administration revealed that the onset, to attenuate  
Page: 148  
ADP-induced platelet aggregation, was similar by either route  
(SA414, page 17; SA111, pages S05135-S05141, S05157-  
S05160). Furthermore, the ex vivo antiaggregatory (ADP) effect  
of SR 25990C after i.v. administration (10 mg/kg) is  
independent of re-absorption of the biliary secreted compound or  
metabolites in the rat (SA 414, page 18; SA137, pages S057552-  
S057553).  
j. Additional rat studies examined the platelet binding dependency  
of SR 25990C to inhibit ADP-induced ex vivo platelet  
aggregation (SA414, page 21; SA110, pages S05062-S05067).  
Rat platelets incubated in plasma treated with SR 25990C were  
not inhibited. Platelet aggregation was inhibited profoundly  
when platelets were treated with SR 25990C followed by  
incubation with SR 25990C-treated or -untreated plasma. These  
data indicate that the activity of SR 25990C is exclusively  
associated with platelets.  
k. Dose-related effects of three days repeat oral administration to  
female and male rats (n=5 each) of SR 25990C, on ADP-  
induced ex vivo platelet aggregation, revealed that as the dose of  
SR 25990C was elevated from 0.625 to 5 mg/kg/day for 3  
consecutive days, that progressively more platelet aggregation  
inhibition resulted (SA414, pages 22-23; SA111, pages S05108-  
S05112, S05113-S05117). The maximal effect occurred at 3  
days post dosing of 5 mg/kg, p.o. Female rat platelets appeared  
to be a bit more sensitive to SR 25990C than male rat platelets.  
Ticlopidine was also assessed for its antiaggregatory effect in  
these studies as well in separate animals (n=5 female and male  
rats each). Ticlopidine was moderately effective in females as an  
inhibitor of ADP-induced ex vivo platelet aggregation at the dose  
administered.  
l. Similarly, dose-related effects of three days repeat oral  
administration to female and male rats (n=5 each) of SR  
25990C, on collagen-induced ex vivo platelet aggregation  
velocity, revealed that as the dose of SR 25990C was elevated  
from 0.625 to 5 mg/kg/day for 3 consecutive days, that  
progressively more platelet aggregation inhibition resulted  
(SA414, pages 24-25; SA111, pages S05108-S05112, S05113-  
S05117). The maximal effect occurred at 3 days post dosing of 5  
mg/kg, p.o. As in the previous study, female rat platelets  
appeared to be a bit more sensitive to SR 25990C than male rat  
platelets. Ticlopidine was assessed for its antiaggregatory effect  
in these studies as well in separate animals (n=5 female and male  
rats each), and was a relatively ineffective inhibitor of collagen-  
Page: 149  
induced ex vivo platelet aggregation velocity, at the dose  
administered.  
m. Dose-related effects of three days repeat oral administration to  
female and male rats (n=5 each) of SR 25990C, on thrombin-  
induced ex vivo platelet aggregation, revealed that the lowest  
dose of SR 25990C evaluated (0.625 mg/kg/day for 3  
consecutive days) was highly effective in inhibiting thrombin-  
induced ex vivo platelet aggregation (SA414, pages 26-27;  
SA131, pages S05221-S05224, S05225-S05228). Female rat  
platelets appeared to be highly more sensitive to SR 25990C in  
terms of inhibiting thrombin-induced platelet aggregation than  
male rat platelets. Ticlopidine was assessed for its  
antiaggregatory effect in these studies as well in separate animals  
(n=5 female and male rats each), and was a relatively effective  
inhibitor of thrombin-induced ex vivo platelet aggregation, but  
not to the degree achieved with SR 25990C.  
n. A similar study to that above, in which the thrombin platelet  
stimulating concentration was elevated from 0.1 U/ml to 1.0  
U/ml (a ten-fold increase) revealed that the inhibition seen in the  
previous study was now completely reversed by the higher  
concentration of thrombin such that SR 25990C was completely  
ineffective (SA414, page 28; SA131, pages S05225-S05228).  
Thus, higher concentrations of thrombin can overcome SR  
25990C-induced platelet inhibition, however the physiological  
relevance of these data is not apparent.  
o. Ex vivo platelet aggregation responses to ADP were also  
evaluated following in vivo administration to rats (n=5) of  
combinations of the levo-rotatory hydrogen sulfate salt isomer  
(SR 25989C) with the dextro-rotatory hydrogen sulfate salt  
isomer (SR 25990C) (SA414, page 30; SA111, pages S05169-  
S05178). SR 25989C did not interfere with the pharmacological  
platelet inhibition achieved with SR 25990C (5 mg/kg) at doses  
of SR 25989C up to 50 mg/kg.  
p. Female rat bleeding time (n=5) was assessed following single  
oral administration of SR 25990C in doses ranging from of 1.25  
to 20 mg/kg (SA414, page 44; SA73, pages S05522-S05523).  
Bleeding time, as assessed by tail transection, increased in a  
dose-dependent manner in response to SR 25990C in all  
animals. The maximal effect on bleeding time occurred at 10  
mg/kg, p.o. Elevation of bleeding time is an expected result  
when utilizing antiplatelet agents. However, excessive elevation  
Page: 150  
of bleeding time is a safety concern and may require adjustments  
to dosage amount and frequency of administration.  
q. SR 25990C was also evaluated on inhibition by ADP of PGE1-  
activated adenylate cyclase in rat and rabbit platelets. In the rat  
study (SA414, pages 64-65) and the rabbit study (SA414, pages  
66-67), SR 25990C at doses of 25 mg/kg, p.o. and 50 mg/kg,  
p.o., respectively, neutralized the inhibition by ADP of PGE1  
activated platelet adenylate cyclase.  
[462] Each of the above studies referred to Sanofi’s factual basis.  
(iii) The ‘777 Patent in vivo Studies  
[463] The ‘777 Patent also describes one of the in vivo studies conducted by Sanofi to assess the  
antithrombotic activity of the compounds. The study described in the ‘777 Patent is the test of  
venous thrombosis on a screw thread described in Toshihiko Kumada et al, “Experimental model of  
venous thrombosis in rats and effect of some agents” (1980), Thrombosis Research 18; 189-203,  
Exhibit 8.  
[464] In this connection, Dr. Shebuski testified that while the model referred to above is primarily  
focused on venous thrombosis, it also provides information on the platelet inhibiting activity of a  
compound (Gheslain Defreyn et al, Pharmacology of Ticlopidine: A Review (1989), Seminars in  
Thrombosis and Hemostatis 15; 159-166 at 163-164, Exhibit 15; J.M. Herbert et al, Clopidogrel, A  
Novel Antiplatelet and Antithrombotic Agent (1993), Cardiovascular Drug Review 11; 180, Exhibit  
16; H. Gerhard Vogel & Wolfgang H. Vobel, eds., Drug Discovery and Evaluation:  
Pharmacological Assays (Berlin Heidelberg: Springer-Verlag, 1997) ch B: Activity on blood  
constituents at 162, Exhibit 9).  
Page: 151  
[465] The efficacy of SR 25990C to prevent venous thrombosis was demonstrated in the rat model  
described above (female rats, n=10/group). The results presented in Table III of the ‘777 Patent  
(page 18) demonstrate that SR 25990C is effective in the dose range of 5-10 mg/kg, p.o. to prevent  
thrombus formation in vivo as is SR 25990E. The racemate (PCR 4099) is similarly effective. The  
levo-rotatory hydrogen sulfate salt isomer, SR 25989C is inactive in preventing thrombus formation  
in the rat.  
(iv) Additionnal in vivo Studies  
[466] In addition to the animal model described above, Sanofi also tested the compounds in other  
animal models and in particular the arterio-venous (A-V) shunt model and the stasis induced  
thrombosis model. This testing is also summarized and explained in Dr. Shebuski’s report at para  
104 and following:  
! The A-V shunt or extracorporeal model is a surgical model in  
which an artery is connected to a vein to provide a new  
conduit for arterial blood to flow through. A silk thread is  
placed in the conduit to elicit thrombus formation. This  
method was reported in T. Umetsu & K. Sanai (1978) “Effect  
of 1-methyl-2-mercapto-5-(3-pyridyl)-imidazole (KC-6141),  
an antiaggregating compound, on experimental thrombosis in  
rats” Thromb. Haemost. 39: 74, Exhibit 17. (Shebuski  
Report, para 105)  
! The A-V shunt model has also been suggested to be  
predictive of the utility of substances which can be used in  
extracorporeal circuits in humans (R.A. Shand et al. (1984)  
“Expression of the platelet procoagulant activity in vivo in  
thrombus formation in an extracorporeal shunt in the rat”  
Thromb. Res. 36: 223, Exhibit 19). (Shebuski Report, para  
108)  
! SR 25990C was evaluated in the rat (female rats, n=5/group)  
A-V shunt model. Single oral dosing of 1.25 to 20 mg/kg,  
p.o. resulted in dose-dependent inhibition of thrombus  
formation in the animal model with the effective dose of SR  
Page: 152  
25990C being between 2.5-5 mg/kg, p.o. (SA414, page 48;  
SA113, pages S05197-S05199). The effectiveness of SR  
25990C was also demonstrated using this model in the male  
rat, at single oral doses of 5-20 mg/kg, p.o. (SA113, pages  
S05194-S05195). (Shebuski Report, para 109)  
! Stasis-induced venous thrombosis can be achieved by simply  
ligating a vein for a period of time. Upon release of the  
ligation, blood flow does not return due to the presence of an  
occlusive thrombus. This method was described by I. Reyers  
et al. (1980) “Failure of aspirin at different doses to modify  
experimental thrombosis in rats” Thromb. Res. 18: 669,  
Exhibit 21). (Shebuski Report, para 110)  
! Evaluation of SR 25990C in another model of venous  
thrombosis (ligation of the inferior vena cava in female rats,  
n=10/group) provided similar efficacy results, in the same  
dose-range, (SA414, pages 54-55; SA89, pages S05565-  
S05571) to the A-V shunt and wire coil models described  
above. (Shebuski Report, para 111)  
[467] Cumulatively, all of the studies described above constitute a positive track-record. These  
tests demonstrated the following:  
!
!
!
L-clopidogrel is inactive in vivo;  
D- clopidogrel is at least as active as the racemate; and  
L-clopidogrel was toxic, but the D was not toxic.  
(iii) Draw-Backs in Factual Basis  
[468] The factual basis for Sanofi’s prediction that the invention under the ‘777 Patent could be  
used in humans must, according to Apotex, be considered in light of both positive and negative  
findings. Regarding the latter, Apotex referred to:  
!
!
the “set-backs” that Sanofi encountered with PCR 3549 and PCR  
5235. Both of these compounds were “active” in animals and  
“inactive” in humans; and  
the convulsions in baboons.  
[469] The Court will address each of the above in turn.  
Page: 153  
a) PCR 3549 and PCR 5325  
[470] Apotex alleges that Sanofi was not forthright regarding its “negative” track-record in the  
development of the compounds leading to clopidogrel bisulfate. In particular, Apotex points to two  
(2) compounds that were originally active in animals but that were then later found to be inactive in  
humans. Apotex argues that, because there was evidence to suggest that the enantiomers of PCR  
4099 may not be active in humans, there was no sound prediction that the activity seen in animals  
with respect to clopidogrel bisulfate would translate to humans.  
[471] Dr. Maffrand, in his evidence, indicated that there were experiments conducted with two  
other compounds: PCR 3549 and PCR 5325. He acknowledged during cross-examination that both  
of these compounds were active in animals but inactive in humans.  
[472] Cross-examination also revealed that Dr. Shebuski, whom the Court recalls is one of  
Sanofi’s witnesses, was not aware of compounds PCR 3549 and PCR 5325.  
[473] The Court agrees with Apotex that Sanofi’s finding with respect to PCR 3549 and PCR  
5325 represent a “draw-back” in the factual basis. However, the Court is of the view that the  
existence of a “draw-back” in the thienopyridine class of compounds does not substantially detract  
from the previously-described positive track record that Sanofi had otherwise established.  
b) Convulsions and Baboons  
Page: 154  
[474] Apotex argues that many of the results obtained by Sanofi regarding convulsions were not  
due to the toxicity of PCR 4099 but were due solely to the proneness of baboons to convulsions.  
Hence, for Apotex, PCR 4099 was not toxic and there were no serious grounds to stop its  
development in favour of the dextro-rotatory enantiomer.  
[475] Dr. Sanders and Dr. Rodricks provided opinions on the matter of convulsions and baboons.  
[476] The question regarding convulsions and baboons is the following: Are the baboons so prone  
to convulsions that a toxicologist would not have been concerned about the toxicity of either PCR  
4099 or clopidogrel to the point he would rule out convulsions in a one-year study at doses as low as  
25 mg/kg?  
[477] While it is true that the record shows that Sanofi’s scientists and toxicologists provided  
comments in studies that baboons may be prone to seizures, Dr. Hirsh, an expert for Apotex, was of  
the view that baboons were a good model for toxicology testing. In reality, the evidence, when  
considered as a whole, does not allow the conclusion that convulsions or seizures in baboons were  
in no way related to PCR 4099. The Court has difficulty accepting the suggestion that a practicing  
toxicologist would not consider such convulsions pertinent to an evaluation of human safety and  
would merely ignore them. While scientists are aware that baboons are species particularly sensitive  
to convulsions, the evidence does not demonstrate that baboons are of no value in scientific study. If  
this were the case, studies would never be conducted on baboons. The convulsions and the study  
results would ipso facto be ignored.  
Page: 155  
[478] Turning to Sanofi’s six-month study on baboons, Apotex emphasizes that the convulsions in  
the six (6)-month study were not considered to be significant. Apotex points to the following  
comment regarding the six (6)-month study on baboons – PCR 4099 at page 15:  
These seizures could not definitely be attributed to PCR 4099  
considering the proneness of baboons to this kind of reactions  
(already observed in previous studies).  
[479] The Court considers that the above-quoted comment does not definitively rule out the link  
between the convulsions and PCR 4099. As explained by Dr. Lacheretz, who was responsible for  
the toxicological studies from the time of the administration in vivo until the autopsy, the above-  
quoted comment cannot be interpreted as a definitive statement. Dr. Rodricks also provided the  
same explanation.  
[480] Further, Dr. Lacheretz explained that the proneness of baboons to experience convulsions  
does not have the same impact on short-term studies as long-term ones. Moreover, the cumulative  
number of studies conducted by Sanofi between 1983 and 1987 make it less likely to conclude that  
the convulsions are necessarily linked to the proneness of baboons and Dr. Rodricks’ explanation  
echoed Dr. Lacheretz’:  
A. And if you look at those results, you see that the number of animals  
having seizures increases with increasing dose. That’s what I’m talking  
about.  
Q. Okay.  
A. I think they were talking about when in the course of the  
treatment did the doses occur. So they saw no pattern. In other  
words, a high dose may have caused a convulsion late, a low  
dose may have caused it earlier. There was no particular pattern  
of when it occurred in an individual animal. But what’s  
important is the finding in 3.1.1 on page 18 which shows the  
total number of events, whenever they occurred, goes up with  
dose. So that’s what I meant in my report when I said this is dose  
related effect and the spontaneous rate – the explanation that it  
Page: 156  
was just a spontaneous occurrence in the baboon is – no longer  
holds when you have data like this. When the dose goes up, you  
get more and more events, you have to believe this is due to the  
drug at this point.  
[Emphasis added]  
(Rodricks, T3582)  
[481] Thus, the Court agrees with both Dr. Lacharetz and Dr. Rodricks that, on a balance of  
probabilities, it is more likely than not that the convulsions were due to the drug PCR 4099 and not  
due to the proneness of baboons to convulsions contrary to Apotex’ assertion.  
[482] Therefore, the Court does not agree that convulsions in baboons were a factor that  
substantially detracted from the positive track record that Sanofi had otherwise established.  
(iv) Conclusion on Factual Basis  
[483] Sanofi obtained results in short-term and long-term studies to support its conclusion that  
there was a factual basis for its prediction that the invention could be used in humans.  
[484] There were important milestones leading to the conclusion that, before the filing date, Sanofi  
had a sound factual basis established by hundreds of studies performed on ticlopidine, PCR 4099,  
and clopidogrel. These studies led to the following:  
!
!
Work on Ticlopidine;  
PCR 4099 was a racemate that was active in animal and human  
models;  
!
!
!
!
PCR 4099 was toxic in a one-year study of baboons;  
L-clopidogrel was inactive;  
D-clopidogrel was at least as active as the racemate;  
L-clopidogrel was toxic, but the D was not toxic.  
Page: 157  
[485] The Court is cognizant of the fact that “draw-backs” have been raised by Apotex. However,  
these “draw-backs” fall short of convincing the Court that the evidence, considered as a whole, does  
not provide a prima facie factual basis allowing Sanofi to conclude as it did. Although there was  
much debate as to whether baboons are prone to convulsions or not, the evidence is not conclusive  
to the effect that the convulsions were a direct result of Sanofi having chosen the baboons as an  
animal model. The observed convulsions might have various causes. The choice of the baboon  
could be central to the occurrence of convulsions but, again, it might not be. There is simply no  
conclusive evidence on this point.  
[486] Relying on the evidence, the Court therefore finds that (i) the length of the one-year study  
from April 1986 to June 1987 on baboons, (ii) the low dosage of 25 mg/kg and, (iii) the number of  
acute toxicity studies conducted between 1983 and 1987 – when read as a whole – provided Sanofi  
with the factual basis to conclude that convulsions were observed in animals receiving PCR 4099  
and the levo-rotatory enantiomer but that no convulsions were observed in animals receiving  
clopidogrel.  
[487] In addition, although there was evidence that Sanofi had tested a compound that was active  
in animals and then inactive in humans, this finding is not strong enough to negate the substantial  
track record established by Sanofi when weighed against all of the other information that Sanofi  
possessed at the time of filing.  
[488] In sum, the Court concludes that there was a factual basis for the prediction that the  
invention would have a use in the treatment of humans.  
Page: 158  
(d) Sound Line of Reasoning  
[489] Now, the Court must turn to the question of whether there was a sound line of reasoning that  
would link the factual basis to the prediction (Eli Lilly Canada Inc. v Novopharm Ltd., 2011 FC  
1288, [2011] FCJ No 1571).  
[490] As Justice Hughes recalled in Pfizer Canada Inc. v Mylan Pharmaceuticals ULC, 2011 FC  
547, [2011] FCJ No 686, at para 242: “[t]hat the line of reasoning is not required to be a “certainty”,  
as long as it is “prima facie reasonable” ”.  
[491] For purposes of determining whether there was a sound line of reasoning, in the case at bar,  
the Court must consider the following elements that would provide the Sanofi scientists with that  
line of reasoning:  
(i) Knowledge of stereochemistry  
(ii) Knowledge of toxicology  
(iii) Knowledge of haematology  
(iv) Knowledge of pharmacology  
(v) Knowledge of previous work on thienopyridine compounds  
(vi) Knowledge of extrapolation from animals to humans.  
(i) Stereochemistry  
[492] Dr. Davies provided the Court with thorough and insightful testimony on chemistry and  
stereochemistry. The relevant portions of his evidence, as set forth in his Expert Report, are  
reviewed next (Davies Report, para 25-44, 53-59).  
[493] Starting from first principles, molecules (including drugs) are composed of atoms. Atoms  
form molecules by precise connectivity rules. These rules involve the joining of atoms by chemical  
Page: 159  
bonds, which are represented by a straight line (—). Most chemical bonds are formed when atoms  
share electrons between them.  
[494] Following the connectivity rules, carbon atoms can bond to four (4) other atoms. If a carbon  
atom forms four bonds with four different atoms (these four (4) separate units are represented by  
different atom connectivities), then there are two (2) possible spatial orientations of these groups. In  
the drawing below, a solid wedge depicts an atom or group oriented toward the viewer, and a  
hashed wedge depicts an atom or group oriented away from the viewer:  
[495] Although these molecules have the same connectivity, they are non-superimposable mirror  
images. This means that, no matter how much you twist or turn these molecules, you cannot make  
one identical to the other without breaking and rearranging the bond connectivities. Such molecules  
are called “enantiomers”.  
[496] Chemists characterise each enantiomer in a given pair of enantiomers based on the spatial  
arrangement, or configuration, of the atoms around the stereogenic carbon atom using the symbols  
“(S)” and “(R).” These designations refer to the absolute configuration (the actual arrangement in  
3D space) based on a standard nomenclature convention.  
Page: 160  
[497] Turning to clopidogrel bisulfate, it belongs to a general class of compounds known as  
“thienopyridines,” named for the bicyclic ring structure containing sulfur (S) and nitrogen (N)  
atoms shown below:  
NH  
S
[498] Clopidogrel bisulfate itself has the following chemical structure:  
O
HSO4  
H
H
S
N
O
*
Cl  
[499] The carbon atom marked with an asterisk (*) is the stereogenic carbon atom. The  
clopidogrel molecule has the (S)-configuration, and in a methanol solution, rotates polarized light to  
-
the right, thus it is called the dextro-rotatory enantiomer. The HSO4 indicates the bisulfate portion  
of the salt molecule.  
[500] In the next figure below, clopidogrel bisulfate is shown on the left, and is compared to its  
corresponding levo-rotatory enantiomer on the right:  
Page: 161  
HSO4  
O
S
S
H
HSO4  
HSO4  
S
H
N
O
H
H
H
H
N
N
(S)  
(R)  
Cl  
OMe MeO  
O
O
Cl  
Cl  
[501] A critical aspect of Sanofi’s sound line of reasoning was its understanding of the structure  
and stereochemical relationship of clopidogrel bisulfate to the previous compounds that had been  
synthesized and tested by Sanofi, including PCR 4099 and ticlopidine.  
(ii) Toxicology  
[502] Both Dr. Sanders and Dr. Rodricks provided the Court with background information with  
respect to toxicology. While the background information provided by Dr. Rodricks addressed the  
issue of toxicity, the Court found it to be overly broad and general. The Court found the background  
information provided by Dr. Sanders to be more instructive. Dr. Sanders has a Masters in  
Pharmacology, is a Doctor of Veterinary Science and has a Ph.D. in toxicology. The relevant  
portions of his evidence, as set forth in his Expert Report, are reviewed next (Sanders Report, page  
11-15).  
Page: 162  
[503] Toxicology is a branch of biology and medicine concerned with the study of the adverse  
effects of chemicals on living organisms. It is the study of symptoms, mechanisms, treatments and  
detection of poisoning.  
[504] Dr. Sanders referred to Dr. Loomis and noted that “toxicity of a given compound can be  
distinctly different within members of a species or between species if the suitable enzymatic  
systems between the test organisms are not identical” (Sanders Report, page 15).  
[505] Toxicological tests are used to define the toxicological response in a test subject to a  
compound in the very specific conditions of the test. Typically, pre-clinical toxicological tests are  
conducted in vitro and in multiple animal systems in a large range of conditions. In the  
pharmaceutical industry, the results of all of these pre-clinical tests are compiled and analyzed to  
arrive at a toxicity profile of the candidate drug under the conditions of the pre-clinical test. This  
profile is then used to design the clinical trials to determine if and how the drug can be given to  
humans and at a level that will be safe so that the effects of the compound in humans can then be  
studied.  
[506] The Court observes that a critical aspect of Sanofi’s sound line of reasoning was its  
understanding of the toxicological relationship and the potential to use pre-clinical toxicity tests to  
predict clinical toxicity.  
Page: 163  
(iii) Haematology  
[507] Both Dr. Hirsh and Dr. Shebuski were accepted by the Court as experts in haematology.  
However, the Court preferred the background information provided by the former as opposed to the  
latter. Indeed, while Dr. Shebuski opined on haematology, many papers he referred to were  
provided to him by counsel, and many of these papers were never before cited by him in his own  
publications. The Court therefore found the background information on haematology provided by  
Dr. Hirsh to be more compelling. The relevant portion of his evidence, as set forth in his Expert  
Report, is reviewed next (Hirsh Report, para 17, 54).  
[508] Hemostasis and thrombosis represent two extreme ends of a spectrum. Hemostasis is a vital  
physiological process that is geared to prevent excessive blood loss when a blood vessel is  
punctured. It acts to retain the fluid nature of blood while ensuring that blood remains within the  
blood vessels.  
[509] Platelets are anucleate blood cells that are key components of normal hemostasis, both in  
ensuring the integrity of blood vessels and aiding in the process of blood coagulation. They are  
present in all mammals, but each animal species has distinctive platelet characteristics, which are  
heterogeneous among different species.  
[510] Platelets are important participants in arterial thrombosis by virtue of their capacity to adhere  
to damaged blood vessels and to clump at sites of injury.  
Page: 164  
[511] When an injury to the vessels occurs, fluid blood is converted into a solid thrombus mass  
made up of fibrin and blood cells.  
[512] Arterial thrombosis is the formation of a thrombus within the arteries. The most important  
factor in arterial thrombosis is platelets, which undergo adhesion, activation and then aggregation as  
a result of vascular wall injury.  
[513] Venous thrombosis is the formation of a thrombus within the veins. Under normal  
circumstances, blood flow in leg veins is maintained by contraction of calf muscles during walking  
and other activities. Most venous thrombi occur in leg veins in regions of sluggish blood flow if  
there is an additional stimulus to blood coagulation.  
[514] It was known by February 1987 that while antiplatelet drugs may reduce the risk of arterial  
thrombosis (but not venous thrombosis or disorders due to extracorporeal blood circuits), this effect  
cannot be dissociated from an increased risk of bleeding. Effective treatment must balance  
antiplatelet inhibition with risk of bleeding.  
[515] In addition to the information above, a critical aspect of Sanofi’s sound line of reasoning  
was its understanding of the following haematology relationships:  
!
!
ADP was known to be involved in the activation of the platelet;  
and  
ADP is common to all species.  
[516] Dr. Hirsh explained to the Court that ADP was known, before the filing date, to be involved  
in the activity of platelets (Hirsh, T511):  
Page: 165  
Q. Okay. And ADP was known to be involved in the activation of the  
platelet?  
A. Well, you mean in this context or  
Q. Generally.  
A. Generally, ADP was known to be involved in platelet activation, yes.  
[517] In addition, Dr. Hirsh confirmed that ADP is common to all species:  
Q. “ADP is a general platelet agonist and induces the basic reaction in all  
mammalian species studied to date.”[as read]  
A. Right.  
Q. True statement?  
A. I think it is, yes.  
Q. So ADP is common to rats, mice, baboons, humans?  
A. When you say “common”, you mean that it is produced by them. Yes.  
(Hirsh, cross T705-706)  
(iv) Pharmacology  
[518] Pharmacology raises the three following issues:  
!
!
Threshold issue: Is pharmacokinetics relevant?  
What is pharmacology? How does pharmacokinetics relate to  
pharmacology?  
!
What do we know about metabolism of clopidogrel and how  
would POSITA know that metabolism is relevant to clopidogrel?  
Threshold Issue: Is Pharmacokinetics Relevant?  
[519] During the trial, a dispute arose over whether Apotex could raise the issue of “metabolism”  
with its experts.  
[520] A pivotal moment arose during the trial when Dr. Maffrand, a leader of Sanofi at the time of  
the ‘777 Patent, acknowledged during cross-examination that issues of metabolism were important  
to the ‘777 Patent. Indeed, Dr. Maffrand knew that primary metabolite “majoritaire” of PCR 4099  
was inactive (Maffrand, T4936). But most importantly, in an affidavit filed before an Australian  
Page: 166  
Court in a case related to the ‘777 Patent, Dr. Maffrand indicated that he had no way of predicting  
what the activity of either enantiomer would be, or how well-tolerated either enantiomer would be,  
even if they could be separated. Dr. Maffrand admitted that he lacked the ability to predict the  
results because he did not know the structure of the active metabolite. In other words, he did not  
know what would be the interaction between the metabolites and the targets:  
Q. You should still have before you, Dr. Maffrand, the Australian  
affidavit. It’s a single document, not bound.  
R. Oui... Non, j’ai dit oui...  
Oui, je l’ai.  
Q. I want to ask you to turn to paragraph 158 of this affidavit. It reads as  
follows:  
“I was also aware, based on my knowledge as a chemist, of the  
risk that even if Mr. Badorc was able to separate the enantiomers  
of PCR 4099, the individual enantiomer might transform back into  
the racemic mixture in the body. This was because the presence of  
the ester function in PCR 4099 could cause the same effect, in the  
body, as I outlined in paragraph 157 above. I had no way of  
predicting what the activity of either enantiomer would be, or how  
well tolerated either enantiomer would be, even if they could be  
separated. I had no ability to predict these results because I did not  
know:  
(a) the structure of the active metabolite;  
(b) the actual target receptors in the body these compounds acted  
on to produce desired and undesired activities; and  
(c) the interactions between the metabolites and the targets.”  
You gave that evidence under oath in Australia, did you?  
R. Oui, j’ai fait la déclaration sous serment. Je ne sais pas si...  
(Maffrand, T4932-4933)  
Q. You should still have before you, Dr. Maffrand, the Australian affidavit.  
It’s a single document, not bound.  
A. I have it now.  
Q. I want to ask you to turn to paragraph 158 of this affidavit. It reads as  
follows:  
“I was also aware, based on my knowledge as a chemist, of the risk  
that even if Mr. Badorc was able to separate the enantiomers of PCR  
4099, the individual enantiomer might transform back into the  
racemic mixture in the body. This was because the presence of the  
ester function in PCR 4099 could cause the same effect, in the body,  
Page: 167  
as I outlined in paragraph 157 above. I had no way of predicting  
what the activity of either enantiomer would be, or how well  
tolerated either enantiomer would be, even if they could be  
separated. I had no ability to predict these results because I did not  
know:  
(a) the structure of the active metabolite;  
(b) the actual target receptors in the body these compounds acted on  
to produce desired and undesired activities; and  
(c) the interactions between the metabolites and the targets.”  
You gave that evidence under oath in Australia, did you?  
A. Yes, I stated this under oath.  
(Maffrand, English RD7535)  
[521] Dr. Maffrand acknowledged that he provided this evidence under oath in Australia. Before  
the Court at trial he seemed uncomfortable with his Australian evidence and finally indicated that  
“he did not agree with himself anymore”. Nonetheless, the exchange between Dr. Maffrand and  
counsel for Apotex left the Court with the understanding that the metabolite issue had its importance  
to the ‘777 Patent and could be relevant in the equation.  
[522] Thus, the issue of pharmacology, and more importantly metabolism, needs to be addressed  
by the Court.  
What is pharmacology? How does pharmacokinetics relate to pharmacology?  
[523] Dr. Levy provided the Court with a comprehensive understanding of pharmacology and the  
relevant portions of his expert report are reproduced below.  
[524] The following definitions were provided:  
!
Pharmacology is the study of the effects of chemical agents of  
therapeutic value or with potential toxicity on biological  
Page: 168  
systems. It includes the disciplines of pharmacodynamics and  
pharmacokinetics.  
!
!
Pharmacodynamics is the study of the molecular, biochemical,  
and physiological effects of drugs on the body, including their  
mechanisms of action.  
Pharmacokinetics is the study of the time course of drug  
absorption, distribution, metabolism and excretion (ADME) and  
the relationship of these processes to the time course and the  
extent of pharmacological effects, therapeutic and toxic.  
[525] There are basic processes that control drug exposure in animals or in humans. Dr. Hirsh, Dr.  
Sanders and Dr. Shebuski all made references to pharmacology. However, Dr. Levy provided the  
Court with an understanding of the process that controls drug exposure in animals or humans since  
drug exposure will determine its effect. This process is known as ADME (absorption, distribution,  
metabolism, and elimination).  
[526] Generally speaking, absorption relates the rate and extent to which a pharmaceutical  
compound enters the body; distribution relates to the way in which the compound is then spread  
throughout the body; metabolism relates to the way the body acts on the compound to change the  
compound and produce metabolites; and elimination relates to the rate and extent to which the  
compound is removed from the body (Levy Report, para 35-83).  
[527] Drug metabolism (also called biotransformation) specifically results from the effects of  
enzymes commonly located in the smooth endoplasmic reticulum of hepatocytes. Metabolic  
reactions are varied including oxidation, conjugation, reduction, and hydrolysis.  
Page: 169  
What do we know about the metabolism of clopidogrel and how would POSITA know that  
metabolism is relevant to clopidogrel?  
[528] Before turning to the discussion on the issue of metabolism, it is important to emphasize that  
clopidogrel is a pro-drug as opposed to an active drug.  
[529] Both Dr. Levy and Dr. Shebuski testified in that respect. They explained that a pro-drug is a  
chemical as it exists before it is administered. It is not active and needs to be transformed. The pro-  
drug will be transformed – i.e. metabolized – when administered and will then become active.  
Basically, it will become another chemical.  
[530] Dr. Levy explained that there are different types of pro-drugs. Some pro-drugs are  
hydrolyzed chemically in the gastro-intestinal (GI) tract, others in the GI membrane, and others in  
the liver. If a drug is unstable in the GI tract, it becomes a source of variability between individuals  
and thus becomes a source of variability. Because the pro-drug must form something else, Dr. Levy  
explained that “we are at the mercy of how that process is affected. When a drug is active by itself,  
we are only at the mercy of it dissolving and being absorbed”. Hence, the compound would need to  
be metabolized in order to work (Levy, T2134-2137).  
[531] Both Dr. Levy and Dr. Shebuski also indicated that the data of some of the tables in the ‘777  
Patent, namely Tables I and II, were ex vivo data. In order to be metabolized, the compound would  
need to be administered into the blood of the animal (rodent).  
[532] The pharmacokinetic/pharmacodynamic relationship is important in order to understand the  
role between a drug and a metabolite. In essence, drugs can be divided into three categories.  
Page: 170  
[533] The first group encompasses most drugs. The administered drug will produce the desired  
effect and all the metabolites are just means of elimination. The second group of drug encompasses  
a minority of drugs and produces metabolites. The metabolites are active. Hence, the metabolites act  
and the drug acts. Finally, in rare cases, there is the third group. This is where the drug itself doesn't  
act and relies completely on the metabolite. Dr. Levy testified that clopidrogrel falls in the third  
category. Its formation of metabolites was essential in order to understand its activity. This “third  
metabolite” is three steps removed. Dr. Levy explained that it automatically creates an  
“unbreachable fire wall” and, thus, any prediction from animal to human is unknown.  
[534] In terms of the line of reasoning, Apotex argues that each of the compounds is itself inactive  
and needs to be metabolized. The consequence of the need to have metabolism in the body is the  
following: the relative activity of the compounds will depend upon how they are treated by the body  
(i.e. when the active metabolite is formed, how it gets distributed). In other words, the ADME  
(absorption, distribution, metabolism and elimination) becomes relevant to these compounds and  
their relative activity.  
[535] Apotex accordingly submits that the prediction relates to the relative activity of compounds  
– the dextro-rotatory enantiomer and the levo-rotatory enantiomer. For example, the dextro-rotatory  
enantiomer versus the combination, the racemic. These are compounds which differ in spatial  
orientation and which will perform pharmaceutically dependent on that spatial orientation related to  
the prediction of stereospecific pharmacokinetics across different species. The ‘777 Patent provides  
rat data and makes the promise across species that the stereospecific pharmacokinetics observed in  
Page: 171  
the rat will be necessarily observed in humans. Apotex argues that this is a prediction without  
substance on the evidence and that there is no question that the compounds have to be transformed –  
i.e. they have to be metabolized – in order to work.  
[536] Apotex further argues that the activity of the compounds depends on ADME and, therefore,  
the predictivity of the activity depends on the predictivity of ADME across different species. Also,  
Apotex alleges that ADME is species-specific and that the evidence supports the conclusion that the  
way compounds are metabolized in the rat is not predictive of how the compounds will be  
metabolized in humans. Consequently, it is difficult to predict relative potency.  
[537] Sanofi did not provide a substantive counter-argument on this exact issue but disagreed and  
argued that metabolites are not needed to pass regulatory hurdles for new drugs. However, Sanofi  
did suggest that, even if metabolism was relevant, there is evidence to show that a laboratory rat and  
a human absorb and eliminate many chemicals in a similar manner (The Laboratory Rat, Baker,  
1980 – exhibit D117 H).  
[538] The issue as raised by Apotex’ contention is thus the following: In the case of human  
toxicity, short of doing tests on humans, is it sufficient to have done a rat test to know the different  
and distinct genetic functionalities, the bodily structures and the enzymes?  
[539] While there was some divergence between the experts on this issue, it is important to  
understand the predictability of the animal models in order to appreciate the line of reasoning. As  
Page: 172  
the Court recalled earlier, it is not required that the line of reasoning be a “certainty” provided it is  
prima facie.  
[540] However, Apotex’ submissions seemed more akin to “certainty” as opposed to prima facie.  
In providing their testimony, certain experts also lost sight of this distinction. For instance, Dr. Levy  
testified that he was looking for a reasonable conclusion and later agreed that this represents much  
more than an inference (Levy, cross T2200). In doing so, the Court is of the view that Dr. Levy  
provided his testimony with a higher threshold in mind (i.e. certainty) as opposed to the legal  
requirement (prima facie).  
[541] The Court finds that, based on the evidence, there is no question that a pro-drug compound  
like clopidogrel has to be metabolized. It was thus critical for Sanofi’s scientists to recognize that  
metabolism was a significant hurdle in the line of reasoning to predict that the invention could be  
used in humans.  
[542] Indeed, in the case at bar, the compound clopidogrel did not stand on its own. It has a history  
and a background. As explained below, clopidogrel was part of a line of thienopyridine compounds  
– ticlopidine and PCR 4099. Hence, on the basis on the evidence adduced at trial, it is relevant to  
assess the previous work from Sanofi on thienopyridine compounds, more particularly ticlopidine  
and PCR 4099. Sanofi referred to that work as the “track record”. This prior work is crucial in order  
to determine later whether the extrapolation from animal to humans is sound. Sanofi’s prior work on  
ticlopidine and PCR 4099 cannot be divorced from the ‘777 Patent and must be addressed.  
Page: 173  
(v) Previous Work on Thienopyridine Compounds  
Ticlopidine  
[543] As mentioned earlier, ticlopidine was discovered in 1972, introduced in France in 1978 and  
then introduced in the US in 1991. The experts’ testimony confirmed that ticlopidine was tested on  
both animals and humans.  
[544] The antiaggregatory effect of ticlopidine was established in ex vivo studies very similar to  
the methods used with PCR 4099 in humans. Furthermore, the antithrombotic efficacy of ticlopidine  
was evaluated in humans based on dose-response studies that had been performed earlier in animal  
models of thrombosis (Thebault et al “Effects of ticlopidine, a new platelet aggregation inhibitor in  
man” (1975) (Clin. Pharmacol. Ther. 18: 485).  
[545] However, because it was discovered in 1985, 1986, and 1987 that ticlopidine had side  
effects, there was a need for a drug that could be administered in lower doses at which side effects  
did not materialize. There was a need for another antiplatelet drug (Hirsh, cross T543).  
[546] This led to the work on PCR 4099.  
PCR 4099  
[547] As discussed earlier in these reasons regarding the factual basis, Sanofi performed a large  
number of studies on PCR 4099. These studies were summarized in an exhibit to Dr. Shebuski’s  
expert report and are attached as Appendix B to these reasons.  
Page: 174  
[548] In addition, Sanofi’s scientists produced a number of investigative brochures regarding PCR  
4099.  
1) Investigational Brochure for PCR 4099 (May 1986)  
[549] The investigational brochure dated May 28, 1986 entitled “Investigational Brochure of PCR  
4099 – an Antithrombotic Agent” stated that “[i]t is generally accepted that platelets have a pivotal  
role in the formation of the arterial thrombus. Hence, it has been assumed that a drug which  
prevented platelet adhesion or aggregation would also prevent thrombosis”. Dr. Hirsh accepted that  
this was a reasonable working theory.  
2) Investigational Brochure for PCR 4099 (January 1987)  
[550] The investigational brochure dated January 1987 is also of interest. It is entitled  
“Investigational Brochure of PCR 4099 – an Antithrombotic Agent” and consists of the third  
edition. It states that PCR 4099 is at least ten (10) times more potent than the parent compound,  
ticlopidine. It is much more powerful (ten fold) than aspirin, while being also effective on animal  
models on which aspirin itself is inactive.  
Summary of Previous Work on Thienopyridine Compounds  
[551] In 1988, Sanofi had significant internal knowledge regarding PCR 4099. It had been tested  
on animals and on humans, and PCR 4099 demonstrated a high antiaggregating effect in rats (and in  
baboons). Also, Sanofi had conducted similar animal testing with PCR 4099 as with clopidogrel.  
Page: 175  
[552] In light of the above, the Court cannot but conclude that the previous work conducted by  
Sanofi on ticlopidine, PCR 4099 and clopidogrel was extensive.  
[553] The Court further recalls that Dr. Hirsh recognized that the similarity of the compounds  
allowed for an extrapolation. Likewise, Dr. Shebuski testified that the pre-clinical studies with PCR  
4099 and with ticlopidine that had been conducted on rats were highly predictive of clinical efficacy  
in humans. The evidence demonstrates that the compounds had a similar structure and metabolism,  
and the Court is of the view that a POSITA would expect that clopidogrel would have the same  
mechanism of action. In cross-examination, Dr. Hirsh opined:  
Q. Okay, but what that abstract seems to tell us is that the mechanism of  
ticlopidine and PCR 4099 appear to be very similar?  
A. Yes, and I would expect that.  
Q. They were both thienopyridines?  
A. Correct.  
Q. And that allows you to do a little bit of correlation or triangulation, I  
am not sure the best word for that. If you see a similar effect in  
similar, structurally similar compounds, it’s easier to make an  
extrapolation?  
A. I think it is, yes.  
(Hirsh, cross T573-574)  
[554] Thus, a critical aspect of Sanofi’s sound line of reasoning was its understanding of history  
with other thienopyridine compounds. This provided Sanofi with a track record of information that  
could be compared and contrasted with the invention in the ‘777 Patent.  
[555] With this in mind, the Court now turns to the following question: Was there a sound line of  
reasoning in the extrapolation from animals to humans?  
Page: 176  
(vi) Extrapolation from Animals to Humans  
Value of Animal Testing  
[556] However trite on the issue of the value of animal testing, the Court observes that millions of  
dollars are spent by pharma companies on research using animals. While it can generally be said  
that animals have some value in science, there was some divergence between the experts with  
respect to the level of predictability for animal models. The overarching issue is therefore not so  
much the value of animal testing (the experts were in agreement in that regard) but rather its  
inference to humans. The issue is to what extent extrapolation from animals to humans is reliable.  
[557] For instance, Dr. Levy opined that based on the animal results in ticlopidine, it was  
reasonable to infer that it had potential use in humans. Dr. Hirsh and Dr. Sanders agreed that a  
correlation had been established between the animal models and ticlopidine and PCR 4099. More  
specifically, Dr. Shebuski indicated that animal models of platelet-mediated thrombosis are  
extremely useful in preclinical studies to determine the safety and efficacy of antiplatelet  
medications (Paul Didisheim, “Animal models useful in the study of thrombosis and antithrombotic  
agents” (1972) Prog. Hemost. Thromb. 1: 165).  
[558] However, while animal testing undoubtedly has value, the experts cautioned against  
automatic extrapolation. In particular, Dr. Sanders and Dr. Rodricks disagreed on the predictability  
of animal testing to humans regarding toxicity and whether the LD50 test was the correct test in  
these circumstances (Table IV of the ‘777 Patent).  
Page: 177  
[559] The evidence adduced before the Court is that, experimentally and scientifically, ticlopidine  
and PCR 4099 were developed through the use of animal models (particularly the rat). On this issue,  
the Court refers to Dr. Shebuski’s opinion “[w]hen we see a correlation like we see here with  
ticlopidine and 4099 in these models, and we have a lot of confidence that if we test some new  
compounds, like the D-enantiomer 25990C, that we will have data that will be very predictive of  
future human clinical efficacy.” (Shebuski, T5053).  
[560] As recalled earlier, a line of reasoning is not required to be “certainty” as long as it is “prima  
facie” reasonable.  
[561] Thus, the Court agrees with Sanofi that a “track record” reflecting a historical perspective on  
events had been established. Ticlopidine and PCR 4099 had shown efficacy and safety in the rat  
model. The animal models used by Sanofi had been used to test two similar compounds, ticlopidine  
and PCR 4099 prior to 1988. Both of these compounds were active in both the animal models and in  
humans. Many of the same tests were used for PCR 4099 and clopidogrel. In light of this observed  
correlation, it was reasonable inference that since clopidogrel was active in the same animal models,  
it would also be active in humans. It was accordingly reasonable to infer that the “track record”  
demonstrated that the animal models were predictive and that the correlation was established before  
1988. In sum, this was sufficient to conclude that testing in rodents would provide an articulate line  
of reasoning that could be extrapolated to humans (Lundbeck Canada Inc. v Canada (Minister of  
Health), 2010 FCA 320, 88 CPR (4th) 325). Although the Lundbeck case was not a selection case as  
argued by Apotex, the Court nonetheless is of the opinion that the general principles outlined in  
Lundbeck apply to the case at bar.  
Page: 178  
(vii)Conclusion on Line of Reasoning  
[562] Based on its review of the evidence, the Court finds that Sanofi’s understanding of the  
following elements was central to its sound line of reasoning:  
!
Stereochemistry: the structure and stereochemical relationship of  
clopidogrel bisulfate to the previous compounds that had been  
synthesized and tested by Sanofi, including PCR 4099 and  
ticlopidine;  
!
!
Toxicology: the potential to use pre-clinical toxicity tests to  
predict clinical toxicity (the toxicological relationship);  
Haematology: ADP is common to all species and was known to  
be involved in the activation of the platelets;  
Metabolism: clopidogrel as a “pro-drug”;  
Previous work on thienopyridine: the track record; and  
Extrapolation: rodents as a good model for extrapolation to  
humans.  
!
!
!
[563] Based on the previously-reviewed evidence which establishes that ticlopidine and PCR 4099  
were active in both animals and humans, the Court concludes that Sanofi established a “track  
record”, which in turn provided a sound line of reasoning upon which to predict that clopidogrel had  
platelet inhibiting activity. This activity was not present in the other enantiomer and clopidogrel was  
better tolerated and less toxic than the other enantiomer and racemate and, in addition, the L-  
clopidogrel was not active.  
(e) Disclosure  
(i) Quid Pro Quo – Principles  
[564] Justice Hughes in Eli Lilly Canada Inc. v Apotex Inc., 2008 FC 142, 63 CPR (4th) 406,  
[Raloxifene], highlighted the importance of the disclosure requirement for sound prediction:  
[163] The third criterion however is that of disclosure. It is clear that  
the ‘356 patent does not disclose the study described in the Hong  
Page: 179  
Kong abstract. The patent does not disclose any more than Jordan  
did. The person skilled in the art was given, by way of disclosure, no  
more than such person already had. No “hard coinage” had been paid  
for the claimed monopoly. Thus, for lack of disclosure, there was no  
sound prediction.  
[164] Eli Lilly argues that there is no need for such disclosure. First,  
it argues that the Hong Kong abstract was already public by the time  
the Canadian filing was made and that was sufficient disclosure to  
satisfy the third element of the AZT requirements. I disagree. A  
considered reading of paragraph 70 of the AZT decision leads to the  
conclusion that the disclosure must be in the patent, not elsewhere.  
The public should not be left to scour the world’s publications in the  
hope of finding something more to supplement or complete a patent  
disclosure. As the Supreme Court said at paragraph 70, the quid pro  
quo offered in exchange for the monopoly is disclosure. It must be in  
the patent.  
[Emphasis added]  
[565] On appeal, the Federal Court of Appeal in Eli Lilly Canada Inc. v Apotex Inc., 2009 FCA  
97, 78 CPR (4th) 388: [Raloxifene for osteoporosis], provided further guidance on the disclosure  
requirement:  
[13] The importance of the disclosure obligation in applying for a  
patent has been emphasized by the Supreme Court of Canada on a  
number of occasions in recent years (Pioneer Hi Bred Ltd. v. Canada  
(Commissioner of Patents), [1989] 1 S.C.R. 1623 at paragraph 23;  
Cadbury Schweppes Inc. v. FBI Foods Ltd., [1999] 1 S.C.R. 142 at  
paragraph 46; Free World Trust v. Électro Santé Inc.2000 SCC 66,  
[2000] 2 S.C.R. 1024 at paragraph 13; Apotex Inc. v. Wellcome  
Foundation Ltd.,2002 SCC 77, [2002] 4 S.C.R. 153 at paragraph 37  
(commonly referred to as AZT and hereinafter referred to as such)).  
[14] The decision of the Supreme Court in AZT is particularly  
significant to the disposition of this appeal. According to AZT, the  
requirements of sound prediction are three-fold: there must be a  
factual basis for the prediction; the inventor must have at the date of  
the patent application an articulable and sound line of reasoning from  
which the derived result can be inferred from the factual basis; and  
third, there must be proper disclosure (AZT, supra, at paragraph 70).  
As was said in that case (para. 70): “the sound prediction is to some  
extent the quid pro quo the applicant offers in exchange for the  
patent monopoly”. In sound prediction cases there is a heightened  
Page: 180  
obligation to disclose the underlying facts and the line of reasoning  
for inventions that comprise the prediction.  
[15] In my respectful view, the Federal Court Judge proceeded on  
proper principle when he held, relying on AZT, that when a patent is  
based on a sound prediction, the disclosure must include the  
prediction.  
[Emphasis added]  
[566] A question arose during the argument phase of the trial regarding whether the discussion by  
Justice Hughes in [Raloxifene] concerning the disclosure requirement for sound prediction had since  
been overturned by the Federal Court of Appeal or whether it was still sound law.  
[567] In the decision of Novopharm Ltd. v Eli Lilly and Co., 2011 FCA 220, 94 CPR (4th) 95,  
[Novopharm] released after the trial ended, the Federal Court of Appeal confirmed that the  
disclosure requirement for sound prediction in Raloxifene is sound law. Justice Evans stated at paras  
46-51:  
(v) Prediction of utility and the need for disclosure  
[46] After concluding that Teva had established that atomoxetine was not  
useful because it had not been demonstrated to be an effective treatment for  
ADHD, the Judge considered whether a POSITA would be able soundly to  
predict the claimed utility. He held that Lilly could not rely on the principle  
of sound prediction because it had not disclosed in the patent the MGH  
Study which was the factual basis of the prediction.  
[47] Lilly submits that neither the Patent Act nor the Supreme Court’s  
jurisprudence requires disclosure of this kind in the patent as a condition  
precedent to successfully invoking sound prediction as the basis of the  
utility of the claimed invention. However, while Justice Binnie may not  
have definitively decided this question in Apotex Inc. v. Wellcome  
Foundation Ltd., 2002 SCC 77, [2002] 4 S.C.R. 153 at para. 70, it has been  
held in the Federal Court, and affirmed by this Court, that a patentee must  
disclose in the patent a study that provides the factual basis of the sound  
prediction: Eli Lilly Canada Inc. v. Apotex Inc., 2008 FC 142, 63 C.P.R.  
(4th) 406, aff’d. 2009 FCA 97, 78 C.P.R. (4th) 388 (Eli Lilly Canada).  
Page: 181  
[48] Counsel argued that Lilly had made an international application for the  
‘735 patent. He relied on Article 27(4) of the Patent Cooperation Treaty,  
1970, 28 U.F.T 7647 (Treaty), which provides that in matters of form or  
contents required for national patent applications, an applicant can insist that  
the relevant provision of the Treaty and Regulations be applied to the  
international application.  
[49] In my view, this argument does not assist Lilly. Article 27(5) of the  
Treaty provides that nothing in the Treaty or the Regulations shall be  
construed as limiting Contracting States’ freedom to prescribe substantive  
conditions of patentability. Writing for this Court in Eli Lilly Canada,  
Justice Noël stated (at para. 19):  
The appellant further argues that requiring the complete  
disclosure of the factual basis underlying the sound prediction is  
inconsistent with the Patent Cooperation Treaty… However, this  
Treaty specifically contemplates the supremacy of national law in  
setting the rules for substantive conditions of patentability (see  
article 27(5) of the Treaty). We are concerned here with  
substantive conditions of patentability.  
[Emphasis in original]  
[50] I see no basis in the present case for departing from the normal practice  
of this Court to follow its own decisions. The decision in Eli Lilly Canada  
was far from being “manifestly wrong” in any of the senses contemplated  
by Miller v. Canada (Attorney General), 2002 FCA 370, 220 D.L.R. (4th)  
149 at para. 10. In view of his ruling on the applicability of Article 27(5), it  
is immaterial that Justice Noël did not refer in his reasons to Article 27(4).  
[51] Indeed, if disclosure in the patent of the factual basis of the prediction  
of utility was not required for sound prediction, it would be difficult to see  
what Lilly could be said to have given to the public, in exchange for the  
grant of the monopoly, that it did not already have. When utility is based on  
sound prediction, disclosure of its factual foundation goes to the essence of  
the bargain with the public underlying patentability.  
[Emphasis added]  
[568] The Court now turns to the disclosure.  
Page: 182  
(ii) Factual Basis  
[569] Sanofi asserts that the factual basis, as disclosed in the ‘777 Patent, is that clopidogrel  
inhibits platelet aggregation. Sanofi asserts that this fact was established in the pharmacological  
studies set out in the ‘777 Patent, including:  
!
!
!
!
!
A description will now be given of the results of this study  
which demonstrates another advantage of the invention, …  
(page 12)  
They demonstrate that the levo-rotatory isomer is inactive and  
the dextro-rotatory isomer is at least as active as the racemate.  
(page 13)  
The results shown in Table II demonstrate again that only the  
dextro-rotatory isomer is active whereas the salts have  
comparable activities. (page 15)  
The results which are presented in Table III show that the levo-  
rotatory isomer is inactive in this test, in contrast to the dextro-  
rotatory isomer and the racemate. (page 17)  
[T]hese results show on the one hand the toxicity of the racemic  
mixture is similar to that of the levo-rotatory isomer whereas the  
dextro-rotatory isomer is markedly less toxic, and, on the other  
hand, that the toxicity depends on the nature of the acid used to  
form the salt. (page 18)  
!
The pharmacological study just presented has demonstrated the  
interesting inhibitory properties towards platelet aggregation of  
the compound Id and the absence of any activity of its isomer Il.  
(page 20)  
[570] However, the Court is of the opinion that upon reading the ‘777 Patent, it does not instruct  
the POSITA that there was a factual basis and a line of reasoning for the prediction that the animal  
studies conducted on rat models could be extrapolated to the prediction that the compound –  
clopidogrel – had a use in humans. The disclosure in the ‘777 Patent is insufficient.  
Page: 183  
(iii) Insufficient Disclosure – Essential Elements of Factual Basis Missing  
[571] The Court is of the opinion that the ‘777 Patent does not sufficiently disclose the factual  
basis and sound line of reasoning for the following reasons:  
!
!
!
!
!
There is no reference to the work done on ticlopidine;  
There is no reference to the work done on PCR 4099;  
There is no reference to multiple animals used;  
There is no reference to knowledge of convulsions; and  
There is no recognition of the importance of metabolism.  
[572] The tests disclosed in the ‘777 Patent are with respect to only one strain of animal, in one  
gender (female), using only a single time point. There was no disclosure of the factual basis or the  
line of reasoning for the prediction. There was no basis for the POSITA to make “the leap” to  
predict use in humans.  
[573] The “track record” is crucial in assisting the POSITA to make the leap to predict use of the  
compound in humans but it is absent from the ‘777 Patent.  
1.  
Missing Information  
(a) No Reference to Work done on Ticlopidine  
[574] The work on ticlopidine, a component of the “track record” was part of the information and  
the benefit known to Sanofi’s scientists. This work would later inform the work on PCR 4099 which  
in turn would eventually lead to work on clopidogrel. The ticlopidine results – or example that the  
dextro-levatory enantiomer was thirty (30) times more potent than ticlopidine – are not found in the  
‘777 Patent. There is simply no mention of ticlopidine in the ‘777 Patent. Reliance upon the results  
of ticlopidine in terms of activity is thus not found in the '777 Patent (Shebuski, cross T5278-5282).  
Page: 184  
(b) No Reference to PCR 4099  
[575] PCR 4099 was a novel antiaggregating agent derived from ticlopidine.  
[576] The Court notes that, while it is true that PCR 4099 was published in various abstracts  
(discussed later in the Anticipation and Obviousness sections of this decision), its properties were  
not part of the general common knowledge. The circumstances are similar to those in the case in Eli  
Lilly Canada Inc. v Apotex Inc., 2008 FC 142, [2008] FCJ No 171, where studies known as the  
“Hong Kong studies” were absent from the patent. Justice Hughes stated that “the public should not  
be left to scour the world's publications”. The same holds true in the present case as far as PCR  
4099 is concerned.  
[577] Specifically, a number of pertinent informative elements relating to PCR 4099, which would  
allow the POSITA to understand the progression from ticlopidine to PCR 4099 and clopidogrel, are  
absent from the ‘777 Patent. For instance:  
!
PCR 4099 is totally inactive in vitro and platelet aggregation and is  
practically inactive after IV administration.  
!
!
!
!
The antiaggregating effect of the PCR 4099 is associated with platelets.  
PCR 4099 is highly potent in rats against the main agonist.  
The antiaggregating effects in baboons.  
The three models of thrombosis used on PCR 4099: i) the arterial venous  
shunt model, ii) the metallic coil model, and iii) the stasis induced  
thrombosis model.  
!
!
!
!
The activity of PCR 4099 could be mediated by metabolite but at this  
time no such active metabolite has been identified.  
The acute toxicity of PCR 4099 was evaluated in two rodent species, rat  
and mouse.  
A sex difference was found in rodents administered with the test  
compound orally.  
Long-term studies of toxicity were carried out in rats and baboons by the  
oral route.  
(Hirsh, Re-Exam T721-728)  
Page: 185  
(c) No Reference to Multiple Animal Models used and Knowledge of Convulsions  
[578] In addition to the above, the Court observes that the POSITA would not know that PCR  
4099 was tested on baboons and rabbits. But more importantly, the POSITA would have no way of  
knowing that convulsions in baboons were allegedly key to the decision to cease the work on PCR  
4099 and to pursue the splitting of the enantiomers. That knowledge was private. It was not public.  
The POSITA would have no reason to know that there is a differential toxicity issue with PCR  
4099. Indeed, even the abstracts on PCR 4099 indicate that there is no problem with the racemate.  
Thus, the POSITA would not be able to deduce that, knowing that the L-enantiomer was toxic, the  
toxicity seen in the one-year baboon study was most likely due to the L-enantiomer which  
comprises 50% of PCR 4099.  
[579] On this point, the Court recalls that the “Simon Memo” dated April 16, 1987, sent by Mr.  
Pierre Simon, Director of Research and Development at Sanofi Research, states that the studies  
conducted on PCR 4099 will cease allegedly due to convulsions. This begs the question: if the issue  
of the convulsions was so important as to halt the studies on PCR 4099 so late in the day and  
following a considerable investment by Sanofi, would it not be important for the reader to know that  
there was a significant toxicity risk with PCR 4099? This information is not in the ‘777 Patent.  
(d) No Recognition of Importance of Metabolism  
[580] The POSITA reading the ‘777 Patent would know that clopidogrel is a pro-drug and would  
therefore understand the importance of metabolism and the “unbreachable firewall” discussed by  
Dr. Levy. Likewise, Dr. Maffrand understood the vital role played by metabolite and testified to its  
Page: 186  
importance. Yet, nowhere in the ‘777 Patent is there a discussion on metabolite. This discussion is  
key in order to disclose this hurdle and allow the POSITA to make the leap.  
2.  
Disclosure: A Reference in the ‘777 Patent  
[581] During final argument, Sanofi submitted that there was a reference to ticlopidine and PCR  
4099 in the ‘777 Patent. More specifically, Sanofi alleged that the ‘777 Patent refers to the Kumada  
paper and that ticlopidine is one of the compounds studied in that paper. Therefore, for Sanofi, the  
reference to the Kumada test means that this was a test that was measured on ticlopidine. In  
addition, Sanofi argues that the ‘777 Patent made reference to PCR 4099. Sanofi further relied on  
page 1 of the ‘777 Patent and argued that it refers to the French racemate patent, i.e. the French  
application 2530247.  
[582] The Court cannot agree with Sanofi’s contentions in this regard. Sanofi’s argument stretches  
the reference to ticlopidine in the ‘777 Patent which implies a weakened duty of disclosure. If an  
element is essential, as the Court deems the progression from ticlopidine, to PCR 4099 and finally  
to the ‘777 Patent to be, it should be in the patent itself and not a couple of steps removed in a  
reference to another document (Eli Lilly Canada Inc. v Apotex Inc., 2008 FC 142, [2008] FCJ No  
171; Eli Lilly Canada Inc. v Apotex Inc., 2009 FCA 97, [2009] FCJ No 404). This issue was  
recently considered by the Federal Court of Appeal in Apotex Inc. v Pfizer Canada Inc., 2011 FCA  
236, [2011] FCJ No 1234, at paras 43-44, where the importance of the bargain of patent law  
inherent in the disclosure requirement was underscored as follows:  
[43] At the hearing, counsel for Pfizer argued that the line of reasoning was  
to be found in the studies listed in the “References” section of the patent  
(Patent ‘132, at pages 30 and 31). Pfizer also took the position that a  
POSITA, taking the prior art as a whole, would be able to infer that  
Page: 187  
multiple doses of latanoprost would give the same results as the single dose  
studies.  
[44] This position seems at odds with the concept of disclosure in patent  
law. In Wellcome AZT, Justice Binnie stated that if utility is not  
demonstrated at the time of filing, the quid pro quo the applicant offers in  
exchange for the patent monopoly is a sound prediction of utility (Welcome  
AZT, at paragraph 70). As the applicant is the one who will benefit from the  
monopoly, I am of the view that only he, and not the authors or inventors of  
the prior art, can discharge himself of the obligation of disclosure. Besides,  
our Court found in Eli Lilly Canada Inc. v. Apotex Inc., 2009 FCA 97, at  
paragraph 17 that a patent that provides no more disclosure than is available  
in the prior art does not provide a sound basis for the prediction.  
[583] Thus, the Court cannot consider any disclosure that, specifically a reference to the patent,  
does not meet the “quid pro quo” inherent to disclosure requirement imposed by patent law.  
(4) Conclusion on Disclosure  
[584] In conclusion, on the question of disclosure, the Court finds that there is insufficient  
disclosure in the ‘777 Patent because it does not disclose the underlying facts (e.g. work on  
thienopyridines and PCR 4099) nor a sound line of reasoning (e.g. ticlopidine, PCR 4099,  
convulsions, metabolism). Thus the underlying factual basis and line of reasoning that grounded the  
inventor’s alleged prediction were not disclosed.  
F.  
Conclusion on Sound Prediction  
[585] Apotex has persuaded the Court that, on balance of probabilities, the disclosure in the ‘777  
Patent was insufficient. For that reason, claims in the ‘777 Patent are found to be invalid for lack of  
sound prediction. Indeed, “…it would be difficult to see what [Sanofi] could be said to have given  
to the public, in exchange for the grant of the monopoly, that it did not already have…”  
(Novopharm, para 51).  
Page: 188  
[586] Given this conclusion, there is no need to address other grounds of invalidity but the Court  
will nonetheless advance its views on the balance of the arguments advanced by Apotex. Hopefully,  
they will be of assistance.  
VIII Obviousness  
A.  
General Principles  
[587] Sanofi’s overall position on obviousness can be summarized as follows: it is admitted by  
witnesses for both parties that a POSITA would have been unable to predict the properties of  
clopidogrel until the racemate, PCR 4099, had first been separated and its individual enantiomers,  
one of which is clopidogrel, tested. Further, clopidogrel has clear unexpected advantages over the  
other members of the genus, which clearly support the patentability of this selection invention.  
[588] As for Apotex, it maintains that the invention in the ‘777 Patent was obvious.  
[589] In Plavix, the Supreme Court of Canada provided a four-step approach for assessing  
obviousness at paras 67 to 69:  
[67] …  
(1) (a) Identify the notional “person skilled in the art”;  
(b) Identify the relevant common general knowledge of that person;  
(2) Identify the inventive concept of the claim in question or if that  
cannot readily be done, construe it;  
(3) Identify what, if any, differences exist between the matter cited as  
forming part of the “state of the art” and the inventive concept of the  
claim or the claim as construed;  
Page: 189  
(4) Viewed without any knowledge of the alleged invention as claimed,  
do those differences constitute steps which would have been obvious  
to the person skilled in the art or do they require any degree of  
invention?  
[Emphasis in original]  
It will be at the fourth step of the Windsurfing/Pozzoli approach to  
obviousness that the issue of “obvious to try” will arise.  
i. When Is the “Obvious to Try” Test Appropriate?  
[68] In areas of endeavour where advances are often won by  
experimentation, an “obvious to try” test might be appropriate. In such areas,  
there may be numerous interrelated variables with which to experiment. For  
example, some inventions in the pharmaceutical industry might warrant an  
"obvious to try" test since there may be many chemically similar structures  
that can elicit different biological responses and offer the potential for  
significant therapeutic advances.  
ii. “Obvious to Try” Considerations  
[69] If an “obvious to try” test is warranted, the following factors should be  
taken into consideration at the fourth step of the obviousness inquiry. As with  
anticipation, this list is not exhaustive. The factors will apply in accordance  
with the evidence in each case.  
(1) Is it more or less self-evident that what is being tried ought to work?  
Are there a finite number of identified predictable solutions known to  
persons skilled in the art?  
(2) What is the extent, nature and amount of effort required to achieve the  
invention? Are routine trials carried out or is the experimentation  
prolonged and arduous, such that the trials would not be considered  
routine?  
(3) Is there a motive provided in the prior art to find the solution the patent  
addresses?  
[590] The Supreme Court of Canada also provided the following additional guidance in assessing  
obviousness, at paras 70-71:  
[70] Another important factor may arise from considering the actual course  
of conduct which culminated in the making of the invention. It is true that  
obviousness is largely concerned with how a skilled worker would have acted  
in the light of the prior art. But this is no reason to exclude evidence of the  
history of the invention, particularly where the knowledge of those involved  
in finding the invention is no lower than what would be expected of the  
skilled person.  
Page: 190  
[71] For example, if the inventor and his or her team reached the invention  
quickly, easily, directly and relatively inexpensively, in light of the prior art and  
common general knowledge, that may be evidence supporting a finding of  
obviousness, unless the level at which they worked and their knowledge base  
was above what should be attributed to the skilled person. Their course of  
conduct would suggest that a skilled person, using his/her common general  
knowledge and the prior art, would have acted similarly and come up with the  
same result. On the other hand, if time, money and effort was expended in  
research looking for the result the invention ultimately provided before the  
inventor turned or was instructed to turn to search for the invention, including  
what turned out to be fruitless “wild goose chases”, that evidence may support a  
finding of non-obviousness. It would suggest that the skilled person, using  
his/her common general knowledge and the prior art, would have done no  
better. Indeed, where those involved including the inventor and his or her team  
were highly skilled in the particular technology involved, the evidence may  
suggest that the skilled person would have done a lot worse and would not likely  
have managed to find the invention. It would not have been obvious to him/her  
to try the course that led to the invention.  
B.  
Date of Invention  
[591] The Court observes that in assessing obviousness under the Old Act, the relevant date is the  
date of the invention (Xerox of Canada Ltd. et al v IBM Canada Ltd. (1977), 33 CPR (2nd) 24  
(FCTD); SCC Plavix decision at para 52). It is for the Court to determine the date of the invention.  
[592] As discussed in Section I there is only one invention in the ‘777 Patent and the invention  
relates to the salts and its advantages. The Court recalls that there is no issue between Apotex and  
Sanofi concerning the inventive concept of the ‘777 Patent.  
[593] The Court further recalls that the inventive concept of the ‘777 Patent was described by the  
Supreme Court of Canada in Plavix at para 78 as follows:  
[78] In the present case, it is apparent that the inventive concept of  
the claims in the ‘777 patent is a compound useful in inhibiting  
platelet aggregation which has greater therapeutic effect and less  
Page: 191  
toxicity than the other compounds of the ‘875 patent and the methods  
for obtaining that compound.  
[594] However, the parties are in disagreement as to the date of the invention.  
[595] Sanofi asserts two possible invention dates. The first one is April 1986 and corresponds to  
the date that Mr. Badorc first successfully resolved PCR 4099. The second date of invention alleged  
by Sanofi is December 1986 which is the date Dr. Fréhel prepared a handwritten first draft of the  
priority application for the ‘777 Patent.  
[596] Apotex, on the other hand, maintains that the date of the invention is between May 1987 and  
November 1987 as the properties of the salts were ascertained during this timeframe.  
[597] Upon considering the evidence, the Court cannot agree with either date advanced by Sanofi  
because neither the date of April 1986 nor the date of December 1986 makes reference to the salts  
which were an integral part of the invention in the ‘777 Patent. While it is true that the date of April  
1986 corresponds to the date when PCR 4099 was first resolved, the properties of the salts at that  
date had yet to be ascertained. As for the date of December 1986, it finds support in a handwritten  
document which refers to tolerability. In that document, Dr. Fréhel writes that it has unexpectedly  
been discovered that the dextro-rotatory enantiomer has the activity for inhibition of platelet activity  
and that the levo-rotatory enantiomer is inactive. Also, the levo-rotatory enantiomer, the inactive  
enantiomer, is less well tolerated of the two enantiomers. However, again, the document does not  
refer to salts.  
Page: 192  
[598] The Court notes that the relevant date for the invention is the date when the inventor can  
prove he has first formulated the invention. This principle was enunciated in Rice v Christiani &  
Nielson, [1930] SCR 443, in Justice Rinfret’s interpretation of the judgment of the Privy Council in  
Canadian General Electric Co. v Fada Radio Ltd., [1930] AC 97, 47 RPC 69, [1930] 1 DLR 449:  
... by the date of discovery of the invention is meant the date at which  
the inventor can prove he has first formulated, either in writing or  
verbally, a description which affords the means of making that which  
is invented. There is no necessity of a disclosure to the public. If the  
inventor wishes to get a patent, he will have to give the consideration  
to the public; but, if he does not and if he makes no application for  
the patent, while he will run the risk of enjoying no monopoly, he  
will none the less, if he has communicated his invention to “others”,  
be the first and true inventor in the eyes of the Canadian patent law  
as it now stands, so as to prevent any other person from securing a  
Canadian patent for the same invention.  
[Emphasis added]  
[599] As such, without the salts, the invention cannot be said to have been reduced to a definite  
and practical shape. Thus, neither the date of April 1986 nor the date of December 1986 can be the  
date of the invention. The evidence demonstrates that the properties of the salts were ascertained  
between May 1987 and November 1987. After considering the evidence, the Court accordingly  
agrees with Apotex that the invention date must be November 6, 1987.  
[600] Thus, the Court will address the question of obviousness as of the date of the invention,  
November 6, 1987.  
C.  
Common General Knowledge  
[601] The Court must now determine the common general knowledge as of November 6, 1987.  
Page: 193  
[602] At issue in this case for assessing the common general knowledge are the following:  
1.  
2.  
3.  
4.  
5.  
6.  
The state of the art of science in 1987  
The ‘875 Patent  
The abstracts and posters at the 1985 and 1986 conferences  
The 1987 FDA Policy  
The Ariens Article  
PCR 4099  
[603] Is the prior art admissible for common general knowledge? In order to be admissible, the  
prior art must have been publicly available as of the date of invention – i.e. November 6, 1987 – and  
it must further be locatable through a reasonably diligent search. The burden is on the party relying  
upon the prior art to establish that it could be found in a reasonably diligent search (Janssen-Ortho  
Inc. v Novopharm Ltd., 2006 FC 1234, 57 CPR (4th) 6), in this case, Apotex.  
[604] The Court also notes that common general knowledge means the knowledge known by the  
person of ordinary skill in the art (Eli Lilly & Co. v Apotex Inc., above, at paras 95-100).  
(1) The State of the Art of Science  
[605] In 1987, the evidence demonstrated that there was a clinical need for a better antiplatelet  
drug. The only such drugs that were available in 1987 were Aspirin and dipyridamole. At that time,  
Sanofi had disclosed ticlopidine, which is part of the thienopyridine compound family.  
[606] In its opening statement, Apotex provided helpful suggestions as to what constituted the  
state of the art of science. In the Court’s view, there are a number of areas mentioned by Apotex that  
should be considered as state of the art of science.  
Page: 194  
[607] In general terms, the state of the art includes the following concepts:  
!
!
!
!
the haemostatic system (including platelet function);  
the principles of stereochemistry;  
the pharmacology and pharmacokinetics of chiral drugs;  
the pre-clinical pharmacological and toxicological testing and its  
limitations;  
!
!
the methods of preparing homochiral compounds;  
the preparation of useful acid addition salts in pre-formulation  
studies; and  
!
the formulation of compounds for human administration.  
(2) The ‘875 Patent  
[608] Sanofi concedes that the ‘875 Patent was in the common general knowledge of the skilled  
person. Dr. Byrn testified in that respect.  
[609] However, Sanofi argues that the ‘875 Patent does not specifically disclose or teach (i) the  
hydrogen sulfate salt of clopidogrel, nor how to obtain the dextro-rotatory enantiomer, nor their  
unique and valuable combination of properties or, that (ii) there are any benefits associated with a  
particular enantiomer or a salt of a particular form.  
[610] In this regard, Apotex argues that the ‘875 Patent asserted that its compounds, including  
PCR 4099 and each of its two enantiomers and their pharmaceutically-acceptable salts (including  
the bisulfate salt), were useful antiaggregants/antithrombotics with excellent tolerance and low  
toxicity, making them very useful for human therapeutic applications.  
[611] It is important to recall that the ‘875 Patent relates to a vast genus consisting of  
approximately 9.5 million different compounds. In particular, the Court notes that the ‘875 Patent  
featured PCR 4099 as the lead compound. Of the many compounds mentioned in the patent, only  
Page: 195  
twenty-one (21) are exemplified. The very first, Derivative 1, is PCR 4099. The results of four (4)  
pharmacological tests on seventeen (17) of the exemplified compounds are given in the ‘875 Patent.  
PCR 4099 and Derivative 10 are the only compounds tested in each experiment. Further, PCR 4099  
is the most potent compound in each test, showing stronger activity at doses lower than the doses at  
which the other compounds were tested. Assuming that a chemist chose example 1 of the ‘875  
Patent and decided to separate it on the basis that Claim 1 of the ‘875 Patent states “are separated if  
desired”, the evidence adduced by Dr. Byrn and Dr. Davies is to the effect that it would have been  
difficult to separate PCR 4099 without undue burden. The ‘875 Patent did not teach the skilled  
reader how to separate or what the advantages of the separation would be.  
[612] After reading the ‘875 Patent and considering the evidence, the Court is of the opinion that  
the ‘875 Patent does not, either directly or indirectly, point to PCR 4099 or to clopidogrel.  
[613] Although it is undisputed that PCR 4099 and clopidogrel are encompassed within the ‘875  
Patent, clopidogrel and its bisulfate salts are not specifically disclosed or claimed in the ‘875 Patent.  
Indeed, the ‘875 Patent does not (i) teach the method to separate or isolate the enantiomer; (ii)  
provide examples on how to prepare enantiomers or, (iii) teach that clopidogrel will be less toxic,  
better tolerated and have better activity.  
[614] However, the Court is of the opinion that the compound PCR 4099 (not its properties),  
Derivative 1 of the ‘875 Patent, would form part of the common general knowledge that a person of  
ordinary skill in the art could find by undertaking a reasonably diligent search of patent applications.  
Page: 196  
(3) The Abstracts and Posters at the July 1985 Conference in San Diego and the June  
1986 Conference in Jerusalem  
[615] Two of Sanofi’s abstracts and posters were the subject of much debate at trial. They are the  
July 1985 San Diego Conference abstract and the June 1986 Jerusalem Conference abstract.  
[616] Sanofi’s scientists made presentations at both of these conferences in San Diego and  
Jerusalem and identified PCR 4099 as its lead compound. The abstracts with respect to the Xth  
International Congress on Thrombosis and Haemostasis held in San Diego were published in  
Thrombosis and Haemostasis in 1985. The abstracts with respect to the Joint meeting of the  
International Committee on Thrombosis and Haemostasis; 32nd annual meeting and the  
Mediterranean League against Thromboembolic Diseases; 9th Congress held in Jerusalem were  
published in Thrombosis Research in 1986.  
[617] The Court observes that in order to be relevant to the issue of obviousness, the posters and  
the abstracts must consist of something which, on the evidence, was either available to a person of  
ordinary skill in the art or that they could reasonably be assumed to have had knowledge of in 1987  
(Mahurkar v Vas-Cath of Canada Ltd. (1988), 18 CPR (3d) 417 (Fed TD), at 432-36, aff'd (1990),  
32 CPR (3d) 409 (Fed CA)).  
[618] Dr. Hirsh explained that, generally speaking, scientists send an abstract in advance of a  
conference. They consist of documents limited in length and size which are then reviewed and rated  
by a scientific committee for the conference at issue. The abstracts that are rated above a certain  
minimal level are accepted either for presentation or for poster presentation.  
Page: 197  
[619] Dr. Colman explained that a participant at a conference, akin to the San Diego and  
Jerusalem conferences in the mid-1980’s, would have received the abstract book before the  
conference meeting. The abstracts are published in a book, and the book is typically sent ahead of  
time to the conference delegates and can be purchased at the conference. The book of abstracts  
would contain an important number of abstracts. At the conference, participants interested in  
learning more about a particular abstract could attend a poster presentation.  
[620] During these conferences, conference rooms were set aside for poster presentations. The  
poster would be displayed in a conference room for a couple of days, usually pinned with  
thumbtacks on the wall. The poster would contain the entire presentation with all the data included  
and the person designated as being responsible for discussing the poster would be there for a shorter  
period of time (Hirsh, T555). Posters could be given out at the meeting. Dr. Colman and Dr. Hirsh  
testified that unless the posters were given out to the participants at the poster presentation, the  
participants would not have received a copy. The posters were not part of the abstract book.  
[621] Against this background, the Court recalls that Apotex argues that the abstracts were  
published in leading journals and regularly reviewed by persons in the field. Sanofi, however, is of  
the view that the abstracts were not available to a POSITA.  
[622] After considering the evidence, the Court agrees with Sanofi and finds that Apotex has  
failed to provide evidence establishing that either the abstracts or the posters could be located by  
way of a reasonably diligent search.  
Page: 198  
[623] Regarding the abstracts in particular, the evidence and notably Dr. Colman’s testimony were  
not conclusive on the issue of whether they could be located in a search or using key words from  
journal indexes at the relevant time.  
[624] Importantly, the Court recalls that, in the mid-1980’s, research was conducted in libraries.  
There was no internet providing information in an instantaneous and electronic fashion. The  
evidence submitted on this point by Apotex based on a recent PubMed search in 2011, while  
interesting, failed to persuade the Court in this regard.  
[625] Indeed, the PubMed internet service search tool presented at trial was simply not available at  
the relevant date. At most, Apotex merely established that the journals could be located using the  
internet in 2011. Further, Apotex’ visual presentation at trial demonstrating that the abstracts are  
currently indexed online by keyword in Science Citation Index (a paper version of Science Citation  
Index was a tool used by skilled researchers and librarians in the 1980’s) does in no way convince  
the Court that a reasonable and diligent search would have allowed the abstracts to be located at the  
relevant date. On the basis of the evidence, the Court does not agree with Apotex’ experts who  
opined that the abstracts would be known by the skilled person or would have been readily located  
by the person of ordinary skill in the art interested in the state of the art of antiplatelet agents.  
[626] Regarding the posters, the evidence adduced by Sanofi clearly establishes that they were not  
published and would not have been available or possibly located by way of a reasonable and  
diligent search. The mere fact that posters on PCR 4099 were displayed at the San Diego and  
Jerusalem conferences is insufficient to convince the Court that they became part of the common  
Page: 199  
general knowledge. Indeed as stated by the Court in Janssen-Ortho Inc. v Novopharm Ltd., at para  
57:  
[57] …[A] public display for three hours at a scientific meeting does  
not mean that the poster has entered into the body of prior art of  
which a person skilled in the art could be said to possess or of which  
they could make themselves aware through a reasonably diligent  
search.  
[627] In addition, although Dr. Colman and Dr. Hirsh testified that thousands of participants,  
academics, pharmaceutical companies with a particular interest in antiplatelet drugs, students and  
clinical practitioners interested in clinical research would attend the conferences of San Diego and  
Jerusalem, the fact of the matter is that a much smaller number of participants would have been  
interested in attending the poster presentation and discussing it with Sanofi’s designated individual.  
Sanofi was not the only pharmaceutical company providing a poster presentation at these  
conferences. There were many other poster presentations to attend in many other conference rooms.  
Although the posters might have been distributed in small numbers, the evidence further  
demonstrates that they did not form part of the book of abstracts and were not published.  
[628] Therefore, the Court finds that the abstracts and the posters from the July 1985 San Diego  
Conference and the June 1986 Jerusalem Conference do not form part of a body of prior art that was  
known to or could in any reasonable way have been found by a person of ordinary skill in the art as  
of 1987.  
(4) The 1987 FDA Manufacturing Guidelines  
[629] Another document was the source of much debate: the 1987 Food and Drug Administration  
in the United States Manufacturing Guidelines (1987 FDA guidelines).  
Page: 200  
[630] The 1987 FDA guidelines stated that racemic new drugs should ideally be separated and  
studied prior to being submitted for approval, and that physical/chemical information should be  
provided or may be requested. Pursuant to the 1987 FDA guidelines, the official FDA policy on the  
issue of stereoisomers would be introduced some years later in 1992 – which is after the relevant  
date. The issue is the following: Can the 1987 FDA guidelines be considered part of the common  
general knowledge as of the date of the invention, i.e. November 1987?  
[631] Sanofi’s position with respect to the 1987 FDA guidelines is that no witness identified this  
document, whereas Apotex argues that in February 1987, the FDA circulated the guidelines.  
[632] As far as the Court is concerned, the origin of the document and the extent of its circulation  
remains a mystery. Neither the testimonies of witnesses nor any related evidence clarified this  
mystery. Indeed, Dr. Wainer testified that he was given the document by counsel for Apotex  
(Wainer, cross T1328). He did not know where the document came from and agreed that it did not  
come from any publication. Dr. Wainer, who worked at the FDA but had left the organization by  
1987, confirmed that he was not on the stereoisomer committee which developed the 1992 policy.  
[633] Dr. Weissinger, for her part, who chaired the FDA stereoisomer committee, wrote the 1992  
Policy and was positioned higher in the hierarchy organization of the FDA than Dr. Wainer.  
Dr. Weissinger testified that she only saw the 1987 FDA guidelines in 1989 after the stereoisomer  
committee was formed. She also testified that she had discussions about the guidelines when she  
was sitting on the FDA stereoisomer committee with one of her colleagues, Mr. De Camp.  
Page: 201  
[634] The Court further recalls that, in cross-examination, Dr. Davies was provided by counsel for  
Apotex with a copy of Dr. Davies’ transcript from the U.S. proceeding (D-190). In that transcript,  
there was a document that was characterized as the 1987 FDA guidelines. This created the  
impression that the 1987 FDA guidelines could have been in circulation at that date. However, the  
evidence establishes that the document Dr. Davies saw in the U.S. proceeding was a different  
document containing a different pagination than the 1987 FDA guidelines. This document states the  
following:  
Note: This Guideline was prepared by Dr. Arthur Shaw, Food and  
Drug Administration, for a Course offered by the Center for  
Professional Advancement in March of 1994. There have been no  
changes in the text from the printed version of the Guideline.  
However, the text has been reformatted to reduce the number of  
pages. The Table of Contents reflects the new pagination. The old  
pagination is noted in the Guideline. (D-190)  
[635] Hence, the document is dated March 1994 and was thus not available prior to that date.  
[636] The Court finds that the evidence relating to the circulation and availability of the 1987 FDA  
guidelines remains unconvincing. There is considerable uncertainty concerning the circulation of  
the 1987 FDA guidelines and whether they were published and, in the affirmative, when they were  
published. At best, the 1987 FDA guidelines were an internal document to the FDA prior to  
becoming policy in 1992. Upon the creation of the FDA stereoisomer committee in 1989, the  
committee started its work and the 1987 FDA guidelines logically became a starting point. Three (3)  
years later, the 1987 FDA guidelines morphed into the 1992 FDA policy.  
Page: 202  
[637] It should also be noted that the 1987 FDA guidelines were also referred to in the case of  
Novo Nordisk Canada Inc. v Cobalt Pharmaceuticals Inc., 2010 FC 746, 86 CPR (4th) 161.  
However, the evidence before Justice Mactavish is in stark contrast from the evidence adduced in  
the case at bar. Furthermore, the date of the invention in Novo was June 21, 1991, which is in a  
different period (in fact a different decade) from the case at bar. Given these differences, parallels  
with the Novo case are difficult to draw.  
[638] Consequently, on the basis of the evidence, the Court concludes that the document entitled  
the 1987 FDA guidelines could not have been located in a reasonably diligent search and cannot be  
considered part of the common general knowledge in November 1987. However, this does not mean  
that there were no discussions regarding the paradigm shift on how to approach racemic drugs. This  
will be discussed later in the decision.  
(5) The Ariens Article  
[639] The Ariens article published in 1984 was referred to on a number of occasions during trial  
and many experts testified to having knowledge of this article.  
[640] Dr. Ariens was thought-provoking and expressed the view that due to the different  
pharmacological and toxicological effects associated with the different enantiomers of a molecule, it  
was an exercise in “sophisticated nonsense” to ignore the stereochemistry of a given compound.  
Dr. Wainer provided a good and helpful summary of Dr. Ariens’ approach.  
Page: 203  
[641] Dr. Ariens was a toxicologist and a pharmacologist who worked in Europe. He began to  
publish that there could be expectation that enantiomers would differ. Dr. Ariens began to do this to  
quantify, codify and examine these differences.  
[642] In particular, Dr. Ariens published a paper entitled “Stereochemistry, a Basis for  
Sophisticated Nonsense in Pharmacokinetics and Clinical Pharmacology”, European Journal of  
Pharmacology (1984) 26: 663-668). In this paper, Dr. Ariens takes a look at how a drug is absorbed,  
metabolized and excreted. Dr. Ariens’ view was that stereochemistry provides the full picture and  
had to be taken into consideration. He posited that the body is chiral and the work has to be  
performed in a chiral environment.  
[643] Dr. Ariens proposed the eudismic ratio. In taking two hands of the molecule (the  
enantiomers), one will be active. The active molecule will be measured and tested in the body. If the  
molecule is the selected one, it will be called eutomer. This study will be repeated with another  
molecule to see whether it is toxic or whether it works in the body. Upon completion of the study, a  
ratio will be established. The usefulness of the drug will then be decided based on a measurement of  
the positive aspects and the negative aspects. This eudismic ratio could then be used to direct how  
drugs are developed.  
[644] The Court also finds that the Ariens article would have been located in a reasonably diligent  
search, and thus formed part of the common general knowledge in November 1987.  
Page: 204  
(6) PCR 4099  
[645] In terms of assessing common general knowledge in 1987, a further question is whether the  
properties of PCR 4099 were generally known. Apotex has not convinced the Court on this point.  
There are in fact two (2) aspects to this question: (1) did PCR 4099 form part of the common  
general knowledge and (2) would the properties of PCR 4099 have been found in a reasonably  
diligent search? Of all of Apotex’ experts, Dr. Hirsh was undoubtedly the one in the best position to  
be aware of the development of novel antithrombotic compounds during the mid-1980’s, as he was  
working in the field at the time. He testified that he was not aware of PCR 4099 until much after  
1987. Another of Apotex’ experts, Dr. Adger, testified that the earliest he became aware of PCR  
4099 was in 1990. The properties of PCR 4099 would not have form part of the common general  
knowledge. This does not, however, mean that the compound PCR 4099 did not form part of the  
common general knowledge.  
[646] The Court observes that, assuming that the posters and abstracts had formed part of the  
common general knowledge, which the Court has ruled out, these posters and abstracts made  
reference to the great potential of PCR 4099 and promised a racemic drug with good activity and  
low toxicity. This wording, more particularly in the abstracts, provided no indication of a problem  
with PCR 4099 and therefore no reason, incentive or motivation leading to a separation of PCR  
4099.  
[647] Thus, the Court concludes that while PCR 4099 did form part of the common general  
knowledge, its properties would not have been found in a reasonably diligent search.  
Page: 205  
D.  
Test of Obviousness  
[648] The Court now turns to applying the four-stage analysis test described by the Supreme Court  
of Canada in the Plavix decision.  
(1) Identify the Notional “Persons Skilled in the Art”  
[649] The qualifications of the POSITA (persons of ordinary skill in the art) are set above in paras  
64-80. The POSITA is a group of individuals, as opposed to one individual, holding a Ph.D. in  
pharmaceutical chemistry, with several years of experience working in the fields of pharmacology  
and toxicology, with good general knowledge of haematology and medicine.  
(2) Identify the Relevant Common General Knowledge of that Person  
[650] Sanofi argues that the parties are in substantial agreement with respect to the relevant  
common general knowledge of the POSITA in 1986/1987. This relevant common knowledge would  
include an understanding of the following:  
!
!
the underlying principles of chemistry including chirality,  
enantiomers, stereoisomers, racemates and optical activity; and  
the knowledge and experience with the general methods of  
resolving racemates.  
[651] However, the parties are not in agreement on two (2) areas that Apotex asserts would form  
part of the common general knowledge of a POSITA. These areas are (i) the alleged 1987 FDA  
guidelines, and (ii) the awareness of the properties of PCR 4099 as a potential antithrombotic agent  
based upon the abstracts and posters.  
Page: 206  
[652] The Court has already summarized what was part and what was not part of the common  
general knowledge as follows:  
!
the knowledge of haemotology / pharmacology / toxicology,  
chirality, enantiomers, stereoisomers, racemates and optical  
activity; and knowledge and experience with the general  
methods of resolving racemates;  
!
!
the knowledge of the ‘875 Patent (but the ‘875 Patent does not  
disclose clopidogrel);  
the abstracts and posters presented at the San Diego and  
Jerusalem conferences were not well known and did not form  
part of the common general knowledge;  
!
!
the 1987 FDA guidelines did not form part of the common  
general knowledge; and  
the properties of PCR 4099 were not part of the common general  
knowledge although the compound of PCR 4099 formed part of  
the common general knowledge.  
(3) Identify the Inventive Concept of the Claim in Question or if that Cannot Readily be  
Done, Construe It  
[653] The Supreme Court of Canada in Plavix, at para 78, identified the inventive concept and  
there is no reason to depart from this concept:  
[78] In the present case, it is apparent that the inventive concept of  
the claims in the ‘777 Patent is a compound useful in inhibiting  
platelet aggregation which has greater therapeutic effect and less  
toxicity than the other compounds of the ‘875 Patent and the  
methods for obtaining that compound.  
(4) Identify what, if any, differences exist between the matter cited as forming part of the  
“State of the Art” and the inventive concept of the claim or the claim as construed  
[654] The evidence adduced in the case at bar demonstrates that none of the prior art describes  
clopidogrel, the bisulfate salt of clopidogrel, a process to make clopidogrel or its bisulfate salts, or  
the beneficial properties of clopidogrel and its bisulfate salt.  
Page: 207  
[655] The evidence is therefore consistent with the Supreme Court of Canada’s finding in Plavix  
at paras 79-80:  
[79] The ‘875 patent disclosed over 250,000 possible different compounds  
predicted to inhibit platelet aggregation. Twenty-one compounds were  
made and tested. Nothing distinguishes the racemate in this case from other  
compounds disclosed or tested in terms of therapeutic effect or toxicity. As  
stated above, there is no disclosure in the ‘875 patent of the specific  
beneficial properties associated with the dextro-rotatory isomer of this  
racemate in isolation; nor was there disclosure of any advantages which  
flow from using the bisulfate salt of the dextro-rotatory isomer. The ‘875  
patent did not differentiate between the properties of the racemate, its  
dextro-rotatory isomer and levo-rotatory isomer or indeed the other  
compounds made and tested or predicted to work.  
[80] On the other hand, the ‘777 patent claims that the invention of the  
dextro-rotatory isomer of the racemate, clopidogrel, and its bisulfate salt  
discloses their beneficial properties over the levo-rotatory isomer and the  
racemate and expressly describes how to separate the racemate into its  
isomers.  
[656] It is thus clear that there is more identified in the ‘777 Patent than what was in the common  
general knowledge.  
(5) Viewed without any knowledge of the alleged Invention as claimed, do those  
differences constitute steps which would have been obvious to the Person Skilled in  
the Art or do they require any degree of Invention?  
[657] The Court recalls that it is at this step of obviousness approach that the issue of “obvious to  
try” arises.  
E.  
“Obvious to Try” Considerations  
[658] In addressing “Obvious to Try” considerations, it is worth noting from the outset that  
“obvious to try” does not mean “worth a try”. The Court agrees with Sanofi that the Supreme Court  
Page: 208  
of Canada used the “obvious to try” test, such that it is self-evident that it ought to work. This test  
represents a different and higher standard than the “worth a try” test.  
[659] In Pfizer Canada Inc. v Apotex Inc., 2009 FCA 8, 72 CPR (4th) 141, at paras 45-46, the  
Federal Court of Appeal discussed the issue of “obvious to try” and “worth a try” and clearly  
rejected the latter:  
[45] In contrast, the test applied by Mr. Justice Laddie appears to be met if  
the prior art indicates that something may work, and the motivation is such  
as to make this avenue “worthwhile” to pursue (Pfizer Ltd., supra, para.  
107, as quoted at para. 42 above). As such, a solution may be “worthwhile”  
to pursue even though it is not “obvious to try” or in the words of Rothstein  
J. even though it is not “more or less self-evident” (Sanofi-Synthelabo,  
supra, para. 66). In my view, this approach which is based on the  
possibility that something might work, was expressly rejected by the  
Supreme Court in Sanofi-Synthelabo, at paragraph 66.  
[46] The Federal Court Judge rendered his decision on the basis that more  
than possibilities were required. He concluded based on the evidence  
before him that Apotex had failed to establish more than that. In so doing,  
he applied the correct test.  
[660] The legal test is thus “obvious to try”.  
[661] In Plavix, the “obvious to try” test was warranted and the Court will look at the following  
factors:  
!
!
Is it more or less self-evident that what is being tried ought to  
work? Are there a finite number of identified predictable  
solutions known to persons of ordinary skill in the art?  
What is the extent, nature and amount of effort required to  
achieve the invention? Are routine trials carried out or is the  
experimentation prolonged and arduous, such that the trials  
would not be considered routine?  
!
Is there a motive provided in the prior art to find the solution the  
patent addresses?  
Page: 209  
!
What was the actual course of conduct that culminated in the  
invention?  
[662] The Court will now address each of these four questions in turn.  
(1) Is it more or less self-evident that what is being tried ought to work? Are there a finite  
number of identified predictable solutions known to Persons of Ordinary Skill in the  
Art?  
[663] The question of “whether it was more or less self-evident that what is being tried ought to  
work” is relevant to the issue of (a) the methods available to separate the enantiomers of PCR 4099  
and (b) the methods available to obtain the salts. The Court must determine whether it would have  
been self-evident to a person of ordinary skill in the art that choosing a method to separate and a  
method to obtain the salts ought to work.  
(a) Methods to Separate  
[664] In order to determine whether what was being tried was obvious – i.e. resolving the racemic  
compound ought to work – the Court must first look at the methods known to separate enantiomers  
and which ones were available in 1987.  
[665] The evidence demonstrates that there were only four (4) methods available to the POSITA  
in 1987:  
!
!
!
mechanical separation of crystals;  
Pasteur method (resolution by formation of diastereomers);  
preparation of pure enantiomers by asymmetric synthesis or  
asymmetric transformation;  
!
chiral HPLC.  
Page: 210  
[666] Out of these four (4) methods, two (2) relevant ones were the subject of debate at trial: the  
Pasteur method and the chiral HPLC method.  
(i) What is the “Pasteur Method”?  
[667] The Pasteur method, also called the diastereomeric salt resolution method, or the “classic”  
method, was developed by the French scientist Louis Pasteur in the 1850s. This method is used for  
resolving racemic compounds in forming and fractionally crystallizing diastereomers. Dr. Adger  
and Dr. Davies opined that it is a method found in leading textbooks, taught to undergraduate  
chemists, and widely practiced for over 100 years. Mr. Badorc informed the Court that he had been  
taught this method during his two (2) year degree in France.  
[668] Apotex argues that the skilled person would understand that PCR 4099 was a compound  
having features that made it particularly amenable to resolution by way of the Pasteur method (as  
well as by chiral HPLC as described below). In particular, Apotex alleges that the compound would  
be recognized as weakly basic (and thus would readily form a salt with a strong chiral acid) and that  
it had a structural similarity to phenylglycine, a compound known to be resolved by the classic  
method.  
[669] As explained by Dr. Adger and Dr. Davies, the Pasteur method involves three (3) steps:  
!
First, the racemic mixture is dissolved in a solvent and is mixed  
with a chiral resolving agent. For basic compounds, like PCR  
4099 (due to the N in the pyridine ring), the chiral resolving agent  
will be an optically active (single enantiomer) acid. A reaction  
then occurs between acid and the base (i.e. PCR 4099) to form  
two distinct salts called diastereomers.  
Page: 211  
!
!
Second, the diastereomers are separated from each other, normally  
by exploiting a difference in the solubility of the two  
diastereomers and retrieving the crystals of the diastereomer that  
are less soluble and thus precipitate out of the solution first.  
Third, each diastereomer is mixed with a base to release the  
separated enantiomer.  
[670] Relying on Dr. Adger and Dr. Davies, Apotex further contends that the skilled person would  
follow a systematic approach to choosing the chiral acid, which was well-described even in the  
textbooks of the day. This approach involved (a) selecting a number of available chiral acids as  
resolving agents; (b) selecting a solvent in which to carry out the reaction; (c) preparing  
diastereomers with each of these acids in parallel experiments; and (d) monitoring and evaluating  
the results of the reaction.  
[671] Apotex also relies on the literature and argues that, if a skilled person follows this rational  
approach, the resolution of organic compounds can be affected with a high probability of success.  
[672] In addition, Apotex submits that because PCR 4099 is weakly basic, the skilled person  
would know to choose strong chiral acids as resolving agents for the screen. These agents would  
definitely include l or d-camphor-10-sulphonic acid, and perhaps tartaric and maleic acid because  
these were inexpensive, commonly available in laboratories, and were known to be strong acids.  
Work by Jacques, Collet and Wilen corroborates Dr. Adger’s view in this regard. In particular, the  
text identifies l or d - camphor-10- sulphonic acid amongst those which have been used to effect  
successful diastereomeric salt resolutions of amines in the past.  
Page: 212  
[673] Although the Pasteur method was well-known and that there were four (4) methods to  
separate the enantiomers, Dr. Davies explained that in 1987, before the single enantiomers were  
separated, it was not possible to predict the properties (i.e. the physical properties, the  
pharmacological properties of activity, absorption, metabolism and excretion, or the toxicity profile)  
of the separated enantiomer based on the properties of the racemate. It is only after the enantiomers  
are tested that one can know whether an isolated enantiomer would have advantages over the  
racemate and the other enantiomer, and possess all of the properties to be useful as a drug (E.J.  
Ariëns, W. Soudijn, P.B. Timmermans, “Stereochemistry and Biological Activity of Drugs”  
(Oxford: Blackwell Scientific Publications 1983) at 89 to102).  
[674] Dr. Davies also explained that there are several reasons for this unpredictability.  
Enantiomers can differ in pharmacological efficacy because they can be absorbed differently,  
metabolized differently, excreted differently, and they can interact in several ways with various  
biological receptors. Nobody can be reasonably certain which receptors will be involved with these  
processes, or how the different enantiomers will interact with them. One can never be reasonably  
assured ahead of time that any of those properties will differ to such a degree as to be clinically  
relevant.  
[675] Dr. Davies mentioned that the skilled person could be deterred from resolving PCR 4099  
because the presence of the ester functionality next to the nitrogen (the amine group) could cause  
the separated enantiomer to racemize back to PCR 4099 in the presence of stomach acid. However,  
Dr. Shebuski opined that the racemization could be avoided with enteric coating. Dr. Davies had  
never heard of enteric coating. Dr. Davies also explained that while the choice of a good resolving  
Page: 213  
agent remains mostly a matter of guesswork or of perspicacity, there are nevertheless some  
instances where the chemist can operate less blindly than in the past (Samuel H. Wilen et al,  
“Strategies in Optical Resolutions” (1977) Tetrahedron 38, at 2725-2736).  
[676] On the basis of the evidence adduced, the Court agrees with Sanofi that, until the POSITA  
had first separated PCR 4099 into its enantiomers, it could not have tested the separated  
enantiomers and, only upon testing, could they have first learned that:  
!
!
!
!
Clopidogrel had antiplatelet aggregation activity;  
This activity was not present in the levo-rotatory enantiomer;  
Clopidogrel was better tolerated than the levo-rotatory enantiomer; and  
The bisulfate salt of CL was more stable than other salts.  
[677] The Court nonetheless agrees with Apotex that the person of ordinary skill in the art would  
be led towards choosing the Pasteur method over the three other potential methods. But in the  
overall context at issue, Apotex has failed to convince the Court that the separation of enantiomers  
was straightforward in every case especially in the mid-1980s. In sum, Apotex has failed to  
convince the Court that the long existing Pasteur method would have worked.  
(ii) Would Persons of Ordinary Skill in the Art turn to this Chiral HPLC?  
[678] The second potential method for racemate separation was chiral HPLC.  
[679] Apotex contends that by 1986-1987 a skilled person would also have known how to resolve  
PCR 4099 using chiral HPLC without difficulty or inventiveness.  
Page: 214  
[680] What is chiral HPLC? Dr. Wainer explained that in chiral HPLC the racemic mixture to be  
resolved is dissolved in a liquid called the “mobile phase”. The mobile phase is passed through a  
column which has been packed with chiral material, known as the “the chiral stationary phase”. The  
two enantiomers of the mixture interact differentially with the chiral stationary phase and, as a  
result, one of the enantiomers proceeds faster down the column than the other. Successive samples  
of what elutes from the column are collected during the period of the separation. Samples of the  
eluent, collected during the period the first enantiomer elutes, will contain that enantiomer.  
Similarly, samples of the eluent collected during the period the second enantiomer is eluting will  
contain the second enantiomer. Similar samples can be combined and extracted to yield the  
individual enantiomers.  
[681] Dr. Wainer opined that the skilled person in 1987 would resolve PCR 4099 using chiral  
HPLC and would choose chiral HPLC and an AGP column for the separation of the enantiomers,  
due to the known chemical properties of PCR 4099:  
!
!
!
!
a steriogenic center in close proximity to an ester group;  
a phenyl ring and a pyridine ring flanking the chiral centre;  
a tertiary amine functionality; and  
its small size.  
[682] The evidence at trial established that HPLC columns were available in 1986-1987 and could  
be used for two purposes: analytical and preparative. The question is whether at the relevant time  
HPLC columns were efficient.  
[683] Dr. Davies testified that in 1986-1987 HPLC columns were only practically useful as an  
analytical technique not as a preparative technique. Hence, while it could be possible to separate  
Page: 215  
racemic material with analytical HPLC columns, the quantities separated would be extremely small  
(i.e. micrograms as opposed to grams) and could not be used on a commercial scale. Dr. Davies  
further testified that if HPLC was used on the analytical front it was not used massively. There were  
some commercial columns available, but they were very expensive and fragile. Mr. Badorc, for his  
part, testified that preparative HPLC columns were simply not available at Sanofi in the relevant  
time period.  
[684] Apotex highlights a paper authored by William H. Pirkle and Thomas C. Pochapsky, “Chiral  
Stationary Phase for the Direct LC Separation of Enantiomer in Advance” (1987) 27  
Chromatography stating that HPLC had reached “prominence” in both analytical and preparative  
separation of enantiomers. Dr. Davies was of the view that the word preparative was more of a  
promise. He did not recall any pharmaceutical company that he came across or any of his academic  
colleagues that were using the preparative HPLC column at the relevant time (Davies, T4621). In  
light of the overall evidence on the use of analytical and preparative columns for the separation of  
enantiomers, the Court accepts Dr. Davies’ testimony in this regard.  
[685] However, while at Smithkline in 1984-1985, Dr. Adger obtained sufficient quantities of  
single enantiomer for pharmacological testing using HPLC (Adger, T1694-1695). But, this event  
remains an isolated one and the evidence does not support the argument that by 1986-1987 the  
HPLC preparative column had become widespread.  
[686] On the basis of the evidence, the Court has accordingly not been persuaded that HPLC  
columns had become common and widespread for the preparative separation of enantiomers. At  
Page: 216  
most, the evidence demonstrates that HPLC columns were available at the relevant time but limited  
to an analytical capacity producing insufficient quantities of a given separated racemic material.  
Thus, the Court finds that the POSITA would not have chosen this method in November 1987 to  
separate the enantiomers.  
(iii) Conclusion on Methods to obtain Separation  
[687] Thus, the question boils down to whether it was self-evident to a person of ordinary skill in  
the art that choosing one of the four (4) methods to separate ought to work.  
[688] The evidence shows that only four (4) methods were available to separate the enantiomers.  
They are the following:  
!
!
!
the mechanical separation of crystals;  
the Pasteur method (resolution by formation of diastereomers);  
the preparation of pure enantiomers by asymmetric synthesis or  
asymmetric transformation; and  
!
the chiral HPLC.  
[689] The Court agrees with Apotex that the mechanical separation of crystals would have been  
discarded by a person of ordinary skill in the art as it is considered a cumbersome process that is  
only applicable in limited circumstances where the racemic mixture is a conglomerate. Asymmetric  
syntheses, likewise, would not have been a first choice due to its difficulty and the fact that it  
produces a single enantiomer in circumstances where each enantiomer is required for testing.  
[690] This would leave two (2) methods to choose from for separating the enantiomers: the  
Pasteur method (diastereomeric salt formation) and the chiral HPLC. Even though there were a  
Page: 217  
small number of methods available to the POSITA, Apotex has failed to convince the Court that, on  
a balance of probabilities, it was self-evident that these methods “ought to work”.  
[691] Indeed, the fact that the Pasteur method has existed for over 100 years guarantees in no way  
a particular result especially when the compound is separated for the first time, which was the case  
of PCR 4099. As for chiral HPLC, it was clear that in the relevant time period it was not available to  
produce the quantities necessary for further testing.  
[692] Moreover, it is only after the enantiomers are tested that one can know whether an isolated  
enantiomer would have advantages over the racemate and the other enantiomer, and whether it  
would possess all of the following properties:  
!
!
!
!
clopidogrel had antiplatelet aggregation activity;  
this activity was not present in the levo-rotatory enantiomer;  
clopidogrel was better tolerated than the levo-rotatory enantiomer; and  
the bisulfate salt of CL was more stable than other salts.  
[693] Thus, although there were a limited number of methods available to the POSITA and they  
would be directed to two (2) methods in particular, it was not self-evident on this basis alone that  
these methods of separation ought to work.  
(b) Methods to Obtain Salt Formation  
[694] However, with respect to the selection of the salts, the Court is of the opinion that it was a  
well-known and well-established methodology at the relevant time and that it would have been self-  
evident that the method to obtain salts ought to work.  
Page: 218  
[695] A salt will form when a reaction is created between an acid and a base. If a compound is  
basic, an acid would have to be chosen. If the compound is weakly basic, a stronger acid would  
have to be chosen and so on. The formation of the salts occurs when an acid and a base react.  
Typically, a “salt screen” is prepared which amounts to the preparation of salts with various  
different acids in parallel so that the salts that crystallize from solution can be quickly identified.  
[696] In this case, the evidence demonstrates that clopidogrel is weakly basic. Consequently, a  
strong acid would be required to form a salt. Sulfuric acids and hydrobromic acids are strong acids  
and would be used for the formation of salts. Dr. Adger explained that this procedure is known as  
the pKa rule of 2.  
[697] More particularly, pKa is the acid dissociation constant at logarithmic scale. It refers to the  
tendency of a given molecule to donate a proton or hydrogen group. The lower the pKa, the stronger  
the acid. When the difference in pKa between the acid and base is greater than 2, a strong salt can be  
expected to form (Byrn, cross T3041; Byrn Report, paras 28-29). The pKa of clopidogrel was  
reported as 4.55 (Byrn, cross T3076).  
[698] Dr. Adger and Dr. Byrn agreed that sulfuric acid would be the first or one of the first acids to  
be included in the screen in making pharmaceutical salt in 1987.  
[699] Mr. Badorc also agreed that strong acids were chosen because they provided a good chance  
of forming crystalline salts (Badorc, cross T4192-4195).  
Page: 219  
[700] Dr. Adger opined that making salts is a routine part of pharmaceutical development and  
commonly used pharmaceutically-acceptable salts have been available in the literature since 1977,  
when an article entitled “Pharmaceutical Salts”, 66 J. Pharm. Sci 1-19 (1977), also known as the  
Berge list, was published.  
[701] However, Dr. Byrn testified that forming a salt was always novel and always inventive  
because it is “completely unpredictable”:  
…But it’s unpredictable, and you can’t be sure that will work. So  
you can’t just limit it. You can’t say, “Oh, I have a strong base, so I  
am going to use only weak acid”. You have to use all of the possible  
acids and bases, and Berge is the one that’s used for this typically,  
and he lists 80 different acids and bases as possible salt formers, so  
the – and then there are many – pardon me, lists 80 acids.  
Clopidogrel is a base, so he lists 80 acids. If it happened to be an  
acid, we’d be interested in the bases because, remember, a salt is a  
reaction of an acid and a base, so since clopidogrel is a base, we react  
it with 1 of the 80 acids.  
(Byrn, T2852-2853).  
[702] Further, relying on articles in the field of salts, Dr. Byrn opined that the selection of the salt  
remains a difficult choice (see Stephen M. Berge, Lyle D. Bighley & Donald C. Monkhouse,  
“Pharmaceutical Salts”(1977) 66 Journal of Pharmaceutical Sciences; Philip L. Gould, “Salt  
selection for basic drugs” (1986) 33 Int’l Journal of Pharmaceutics; P. Heinrich Stahl & Camille G.  
Wermuth, eds, Handbook of Pharmaceutical Salts, Properties, Selection, and Use (Zurich: Verlag  
Helvetica Chimia Acta, 2002).  
[703] Overall, the Court prefers Dr. Adger’s approach to Dr. Byrn’s. The evidence clearly  
demonstrates that salt selection was present in the literature. More particularly, the Berge list refers  
Page: 220  
to eighty (80) acids for forming salts with drug compounds that are basic and twenty-one (21) bases  
are listed for forming salts with drug compounds that are acidic. The fact that clopidogrel was a  
weak base would lead the person of ordinary skill in the art to choose a strong acid and both experts  
agreed that sulfuric acid would be at the top of the list.  
[704] Mr. Badorc himself provided evidence to the effect that methods for obtaining salts were  
well-established. Indeed, Mr. Badorc testified that he was cognizant of the pKa rules of 2 when he  
decided to form salts of clopidogrel. He also acknowledged selecting the acids for salt formation  
based on the well-known Berge list.  
[705] Mr. Badorc further testified that although bisulfate salt was not listed on the FDA list it was  
listed on the non-FDA list. Mr. Badorc also admitted that he knew about the non-FDA list and that  
the non-FDA list was approved in France at the relevant time and that he had access to this list.  
[706] For all of these reasons, the Court accordingly finds that the few methods to obtain salt  
formation were well-known and a well-established methodology at the relevant time.  
(c) Conclusion: “Ought to Work”  
[707] The Court therefore finds that at the relevant time, the Pasteur method could not guarantee a  
specific result and the chiral HPLC method could not produce sufficient quantities of the separated  
racemic material and was not yet widespread. However, on the basis of the experts’ testimony and  
the inventor’s own admissions, the Court concludes that the methods for salt formation were readily  
available and commonly used to make pharmaceutically acceptable salts.  
Page: 221  
[708] Thus, the Court is of the opinion that, while it was not clear that it was self-evident to the  
POSITA that the methods of separation ought to work, it was clear that the method of salt  
preparation would work.  
(2) What is the extent, nature and amount of effort required to achieve the Invention? Are  
Routine Trials carried out or is the Experimentation prolonged and arduous, such that  
the trials would not be considered routine  
(a) What is “Routine” in separating the enantiomers of PCR 4099 and obtaining the  
salts  
[709] The Court finds that the POSITA would have been directed towards the classic Pasteur  
method to separate. In turning to this method, based on the evidence, the Court is of the opinion that  
the method was routine.  
[710] Sanofi argues that the definition of routine does not encompass inventive work which  
amounts to making a new compound for the first time. Sanofi further alleges that the first time any  
experiment is conducted there is uncertainty as to the result because one does not know if the  
experiment will work as hoped or what the result will be. This is in contrast to what is truly routine,  
namely an experiment that has been performed many times before with the same components and  
under the same conditions, each time giving the same result (e.g. regulatory quality control testing).  
[711] Sanofi also submits that its definition of “routine” is consistent with the meaning ascribed to  
this notion by the Supreme Court of Canada in Plavix. In that case, the Supreme Court of Canada  
noted that there were known methods for separating racemates and known methods for testing the  
properties of the enantiomers and salts. However, it was found that such experimentation was not  
Page: 222  
routine. Thus, for Sanofi, using known techniques to identify something that was previously  
unknown is unobvious.  
[712] More specifically, Sanofi maintains that the evidence clearly establishes that it was not  
obvious that one could successfully separate PCR 4099. Even if PCR 4099 could be separated, it  
was far from obvious that advantages would result from the separation. Frequently one would either  
get no benefit, for instance in the case where the activity and toxicity are the same as between the  
enantiomers or where there is racemization in vivo.  
[713] Dr. Adger generally agreed that drug discovery is never certain. However, some process to  
obtain a drug can sometimes be easier than others. Dr. Adger mentioned that it is never a trivial  
matter.  
[714] Dr. Byrn discussed the fact that salts including salt screen involve a level of difficulty and, in  
some cases, will not necessarily work.  
[715] Against this background, the Court observes that Sanofi appears to suggest that making a  
new compound for the first time amounts to an invention. This cannot be so. The making of a new  
compound for the first time cannot be an invention all the time. It remains a question of fact to be  
assessed on a case-by-case basis.  
[716] Specifically, based on the evidence tendered, the Court cannot agree with Sanofi because the  
work of Jean Jacques, André Collet & Samuel H. Wilen in a 1981 publication Enantiomers,  
Page: 223  
Racemates, and Resolutions (p 384), indicates that ethanol, methanol or acetone were solvents most  
commonly used in diastereomeric salt resolution (Pasteur method).  
[717] The Court agrees with Apotex that the literature confirms that camphozxcr-10-sulfonic acid  
and tartaric acid had been used to resolve phenylglycine and its methyl ester. Indeed, there are  
precedents in the literature. For instance, as early as 1925, A. W. Ingersoll reported the resolution of  
phenyglycine by diastereomeric salt formation using camphor-10-sulphonic and the resolution of  
the methyl and isopropyl esters of phenyglycine was achieved by John C. Clark in 1976 using  
tartaric acid. The Court notes that Dr. Davies did not challenge Dr. Adger’s comments regarding the  
precedents for the diastereomeric salt resolution.  
[718] The evidence also demonstrates that Phenylglycine Methyl Ester has a similar structure to  
PCR 4099 (P-154):  
[719] The skilled person would be expected to know about this. Indeed, Dr. Davies was of the  
view that a “chemist has to know everything that is in the literature in the area that he is working”  
Page: 224  
and Dr. Adger recalled the simple reality that “… spending a day in the library can save you a week  
in the lab …” (Adger, T1561-1562).  
[720] The skilled person would thus review the literature and, based on other experiments, would  
find out that there is a “guide”. On the basis of the existing literature and the previous work on  
Phenylglycine, the Court is convinced that the resolution of PCR 4099 would be accomplished by  
the skilled person using the diastereomeric salt resolution methodology and this would have been  
routine.  
(3) Is There a Motive provided in the Prior Art to find the Solution the Patent addresses?  
[721] When assessing whether a motivation was provided in the prior art, the Court will look as to  
whether there is more than a mere possibility in this regard. This approach was explained by the  
Federal Court of Appeal in Pfizer Canada Inc. v Apotex Inc., above.  
(a) Motivation to separate: the “Mumblings” of the Mid-1980’s  
[722] Was there a motivation to separate the enantiomers of PCR 4099 in 1987? This issue  
sparked an interesting debate between the parties.  
[723] While there were undoubtedly discussions on the issue of separating enantiomers in the  
scientific community in the mid-1980’s, the real question is whether these discussions had reached  
such a level that the person of ordinary skill in the art working in the field in 1987 would have been  
motivated to separate the enantiomers. Was there an understanding that regulatory agencies would  
have expectations or/and requests in that regard? Had these expectations turned into policies?  
Page: 225  
[724] In this connection, the Court must consider the key events in chronological order until the  
relevant time which fed into the “mumblings” surrounding the separation of enantiomers and then  
assess whether the intensity of the “mumblings” was such that it may have led to a motivation to  
separate the enantiomers of PCR 4099.  
Event 1: The Thalidomide Disaster  
[725] Thalidomide was a compound approved and administered in Europe and in the United  
Kingdom in the late 1950’s. It was widely used in Europe for conditions that were associated with  
morning sickness experienced by pregnant women. But thalidomide had a teratogenic property with  
one of the less active isomers. Consequently, many infants were born with severe birth defects as a  
result of their mother having taken thalidomide. Dr. Sanders referred to thalidomide as the  
“thalidomide disaster”. He testified that, as a consequence, the principles of stereochemistry in  
biological systems, and examples of stereoisomers that differed markedly in pharmacological and  
toxicological action (e.g. thalidomide), were well known to toxicologists well before 1988.  
[726] Dr. Wainer explained that applications were made in the United Sates for thalidomide.  
However, Dr. France Oldham Kelsey, an FDA review pharmacologist, refused to allow thalidomide  
in the United Sates and blocked the sales of thalidomide. Dr. Wainer testified that Dr. Kelsey made  
that decision based on the literature and thought that “something was not right about thalidomide”.  
Thalidomide was thus prevented from entering the American market.  
Page: 226  
Event 2: The 1985 Japanese Guidelines  
[727] Dr. Wainer testified that in 1985, Japanese regulators adopted and published pharmaceutical  
manufacturing guidelines directing sponsors of applications for racemic drugs to separate and  
characterize the enantiomers (Wainer Report, Tab 23). These guidelines provide that “[d]epending  
on the type of pharmaceutical substances, there are times when the results of other additional  
antigenic tests may be required. Hence, if it is known that the pharmaceutical substance has special  
antigenic properties or causes adverse reactions due to such antigenic properties, an investigation  
and study of those properties, at the very least, should be conducted”.  
[728] Dr. Davies stated that he wasn't aware of the Japanese guidelines being published, but he  
knew of their existence and agreed, on the basis of an earlier statement in a proceeding in the United  
States, that there were discussions about the Japanese document in the scientific community in 1985  
(Davies, cross T4565).  
Event 3: Dr. Kumkumian’s 1986 Speech  
[729] Dr. Wainer opined that by 1986, the FDA had come to expect that sponsors of racemic drugs  
were to resolve and characterize the pharmacological and toxicological properties of racemic drugs  
and that the excuse that this was a difficult task would no longer be accepted.  
[730] In March 1986, a major scientific international meeting - the 133rd Annual Meeting of the  
American Pharmaceutical Association in San Francisco, California - was attended by thousands of  
participants working in the drug development community. Dr. Kumkumian, Assistant Director of  
Chemistry at the FDA at that time, declared in a speech before a very large audience that sponsors  
Page: 227  
of applications for racemic drugs in the United States were expected to discuss the results of studies  
carried out to investigate the physical, chemical and biological properties of single enantiomers.  
Dr. Wainer, who worked at the FDA at the time and participated at the conference, provided the  
Court with the context surrounding the Kumkumian speech.  
[731] In his speech, Dr. Kumkumian stated the following:  
Many chemicals that exist contain stereoisomers and in which biochemical  
differences have been shown among these isomers. In glutamic acid, for  
example, only the dextrorotatory isomer functions as the well known flavor  
enhancing agent. In aspargine, only the dextro isomer is sweet. In regard to  
the well-known drug chloramphenical, only one of the four isomers acts as  
an antibiotic. The differences in behavior of enantiomers in living matter  
are explainable by the fact that reactions in living matter are catalyzed  
largely by optically active enzymes or need to compliment stereospecific  
receptors…  
As we are aware specific isomers may not only have quantitative  
differences in comparable activity with their “opposite” isomers but do, in  
some instances, have qualitatively different pharmacologically,  
therapeutically and pharmacokentically. Of the four stereoisomers in  
propoxyphene, only the dextro isomer of the alpha racemate exhibits  
analgesic properties in contrast to the levo form which is marketed as an  
antitussive agent.  
(Page 7)  
As we can see from these examples, individual stereoisomers can have  
various effects for their counterpart isomers in a drug molecule consisting  
of a racemate. These considerations should be addressed in evaluating the  
safety, effectiveness and quality of the drug product.  
(Page 9)  
Whether a sponsor of an IND decides to go with a specific isomer or a  
racemate it should be clearly delineated in the original submission. The data  
submitted on substances that do or can exist as stereoisomers should  
include a discussion of the possible isomers which may result from the  
method of the manufacture and the results of studies carried out to  
investigate the physical, chemical and biological properties of these  
isomers.  
(page 12)  
Page: 228  
(Kumkumian, Charles. “Regulating the Enantiomeric Purity of  
Pharmaceuticals: The FDA’s Point of View”, presented at the 133rd Annual  
meeting, American Pharmaceutical Association, San Francisco, California,  
March 19, 1986)  
[Emphasis added]  
[732] This above-quoted statement by the Assistant Director of the FDA’s Office of Drug  
Research and Review intended to send a message to a large audience: the FDA wanted racemic  
drugs to be resolved and their enantiomers characterized. By these remarks, the FDA was providing  
information about its direction in the future. This direction, crafted in the 1987 FDA guidelines,  
would eventually crystallize and become the FDA policy in 1992.  
Event 4: The 1987 FDA Guidelines Document and the Stereoisomer’s Committee  
[733] Dr. Weissinger testified that, due to some confusion with respect to the stereoisomers policy,  
she was asked to co-chair a committee with Dr. Kumkumian and draft a policy for the FDA  
regarding these compounds. The stereoisomers committee was set up in 1989. The same year,  
Dr. Weissinger wrote a paper informing the pharmaceutical community that the FDA “was going to  
come up with a policy and that we were meeting to do this and we had a new committee and what  
the committee's charge was” (Weissinger, T2580-2582).  
[734] The stereoisomers committee conducted an evaluation and eventually Dr. Weissenger wrote  
what would become the 1992 FDA policy.  
Event 5: The 1989 Nature Article and the Pressure for New Drugs  
[735] It is worth noting that in 1989 (two years after the relevant date at issue in this case), in the  
leading and well-respected scientific journal Nature (vol. 342 no.6250), Dr. Davies wrote that “the  
Page: 229  
differing pharmacological effects of the two enantiomers of chiral molecules are now well  
documented”. He added: “[w]e are at the watershed of asymmetric synthesis – in the near future it  
will be common practice to synthesize all potential new drugs as single enantiomers and there is  
already pressure from regulatory agencies in this direction” [Emphasis added]. This statement is in  
large part a reiteration of Dr. Kumkumian’s speech.  
[736] Also, the Court agrees with Dr. Davies that, as a whole, the literature did not suggest to an  
ordinary chemist in 1987 how to obtain the enantiomers. The writings of Dr. Davies in 1986 and  
1987 seem to suggest that there was recognition that enantiomers of a molecule could have different  
effects. For instance, Dr. Davies wrote in 1986 that “it is now recognized widely that the two  
enantiomers of a molecule can have a different in vivo effect. For this reason, the search for novel,  
more efficient and, most importantly, more general methods for the synthesis of enantiomerically-  
pure organic compounds is intensifying” (Asymetric synthesis – Prospects for industry:  
Stereoselective synthesis via arene chromium tricarbonyl complexe, 1986 p 173) [Emphasis added].  
He also wrote in 1987 that there was a “growing appreciation of the different biological effects of  
enantiomeric molecules”.  
[737] On the basis of the above, and considering that published papers or articles are generally  
submitted six (6) months to a year prior to publication, the Court concludes that leading chemists in  
the area of drug discovery were aware in 1989, or before, that “there is already pressure from  
regulatory agencies [toward separation]” [Emphasis added].  
Page: 230  
Event 6: Joint Venture Partner Asking about Data on Enantiomer  
[738] In the mid-1980’s, Sanofi was involved in a joint venture with certain Japanese companies.  
Of interest is an internal Sanofi letter dated September 29, 1986, which was sent to high-ranked  
individuals including Mr. Pierre Simon. This letter consisted of a request from the Japanese Joint  
Venture and specifically concerns the enantiomers of PCR 4099. It mentions the following on p. 2  
at B. under the heading Health Authorities: “within the context of the Japanese Joint Venture, we  
have been asked for “separation and study enantiomers” without further details” [Emphasis added].  
[739] This same letter also makes reference to a similar request from the FDA:  
MEIJI-SEIKA and TAISHO have been told that the work is in  
progress on these enantiomers. But they have not been sent any  
report. Regarding the FDA, the telex from A. URDANG (Sept. 16.  
1986) queried on this subject by W. CAUTREELS, is in the same  
vein.  
[740] At trial, Dr. Maffrand did not provide any further explanation regarding the above-quoted  
paragraph. He testified in cross-examination, that he did not know A. Urdang and that the telex  
referred to in the letter was requested in the American proceedings but was never located.  
Event 7: The 1992 FDA Policy In Force  
[741] Dr. Weissinger testified that the FDA policy on stereoisomers came into force on May 1,  
1992, and that prior to 1992, there was no coordinated policy on how to handle stereoisomers drugs.  
[742] Therefore, the FDA’s 1992 policy would signal a long-term change in the pharmaceutical  
landscape, as this new policy generally required that all new chiral drugs be tested to determine if a  
pure isomer form would eliminate unwanted side effects.  
Page: 231  
(b) Summary  
[743] On the basis of the evidence, the “mumblings” with respect to enantiomers and their  
different effects started in the early 1980’s and clearly intensified in the mid 1980’s. While it is true  
that the FDA policy was crystallized with its release in 1992, nevertheless, stereoisomers were a  
topic of interest in the mid 1980’s. The 1992 FDA policy represents the final outcome of  
discussions and changes that were well underway in the 1980’s. Hence, the Court is of the view that  
the 1992 FDA policy does not represent the beginning of knowledge and awareness. Prior to 1992,  
there were important milestones and clear indicators that the landscape was already shifting.  
[744] As early as 1985, the Japanese regulators had published pharmaceutical manufacturing  
guidelines. The same year Sanofi was told by way of a letter received from a joint venture partner  
that the Japanese regulators were inquiring into separation of the enantiomers. This same letter also  
made reference to a similar request by the FDA. Although the telex regarding that letter could not  
be found, the fact remains that a Sanofi document refers to the regulatory requests from Japan and  
the United States regarding the separation of enantiomers.  
[745] Also in 1986, Dr. Kumkumian made an important presentation to a large audience and  
outlined the expectations of the FDA for the years to come – i.e. that the properties of enantiomers  
would likely become a requirement for the regulatory process. Dr. Wainer, who worked at the FDA  
until 1986, testified with respect to the change of culture and the expectations within the FDA in the  
mid-1980s.  
Page: 232  
[746] The evidence shows that in the mid-1980’s, there were clearly discussions and heated  
debates with respect to the separation of enantiomers. In an article published in 1987, authors stated  
in the Journal of Medicinal Chemistry that “there were great interests in investigating enantiomers”  
(P-178). Likewise, Dr. Maffrand testified to the fact that although there were no formal regulations  
in place, there were discussions in this regard amongst the health authorities in the United States.  
Dr. Maffrand added that although it was not a major element in deciding to separate the PCR 4099  
enantiomers, it was nonetheless taken into account. In addition, Dr. Maffrand stated that the  
discussions were occurring in the scientific community before the decision to separate the  
enantiomers of PCR 4099 was made (Maffrand, T4928):  
Q. And those discussions in the scientific community were ongoing at  
the time you made the decision to separate the enantiomers of 4099.  
Is that correct?  
R. Oui, c’est ce que j’ai dit. Mais elles existaient déjà depuis plusieurs  
années.  
Q. And those discussions in the scientific community were ongoing at the  
time you made the decision to separate the enantiomers of 4099. Is that  
correct?  
A. Yes, that’s what I said. They existed for a number of years already.  
They had been going on for a number of years.  
[747] Dr. Davies suggested that drug companies would avoid resolving racemates for fear of  
finding a better compound but, in light of the overall evidence, the Court does not accept  
Dr. Davies’ testimony on this point. Significantly, it is inconsistent with the fact that Sanofi was  
already resolving enantiomers during this period – e.g. PCR 1033 and PCR 3549.  
[748] It is accordingly difficult to conclude that a person of ordinary skill in the art would not have  
been aware of the on-going discussions which were taking place on the issue in the mid-1980’s,  
Page: 233  
unless it deliberately chose to ignore them. At the very least, in 1986-1987, there was a clear  
indication that the separation of enantiomers could be performed and it was therefore important to  
test for them in order to pre-empt what was to come.  
[749] It follows that although the FDA’s official policy was released in 1992 and that the  
document entitled “1987 FDA Guidelines” was never published or circulated, the evidence indicates  
that the literature, Dr. Kumkumian’s speech, the expectations of the Japanese regulators, and the  
intense growing “mumblings” around stereoisomers, all reflected the content and spirit of the 1987  
FDA guidelines at the relevant point at issue. The discussions and the expectations in the scientific  
community had reached the level where the line was drawn in the sand. At the relevant date, the  
paradigm had shifted.  
(c) Conclusion: “Motivation”?  
[750] For all of these reasons, the Court finds that the person of ordinary skill in the art would  
therefore have had the motivation to separate the enantiomers of PCR 4099. In reaching this  
decision the Court is aware that it has to remain cautious that “obviousness” does not provide  
disincentive for innovation (SCC Plavix, paras 64-65).  
[751] The Court will now address what was the actual course of conduct that culminated in the  
invention.  
Page: 234  
(4) Actual Course of Conduct that Culminated in the Invention  
[752] Dr. Maffrand was not named as an inventor of the patent but it was Dr. Maffrand’s idea to  
separate the enantiomers of PCR 4099. He asked Mr. Badorc and Dr. Fréhel to separate the  
enantiomers (Maffrand, T4792-T4793).  
[753] Although not raised as an issue in this case, the Court questions whether Dr. Maffrand  
should have been named as an inventor in the ‘777 Patent. However, this issue is not before the  
Court and will not be addressed in this case.  
[754] Mr. Badorc obtained a diploma of technology in chemistry in 1972 at the Université de  
Rennes in France, where he learned the diastereomeric salts method of separation. Separating the  
enantiomers of PCR 4099 was not Mr. Badorc’s first separation of a compound. He had previous  
separation experience with other compounds – namely PCR 1033.  
PCR 1033  
[755] In 1975, PCR 1033 was tested for antiplatelet aggregation activity and it appeared that PCR  
1033 could be considered as a candidate for development as antiplatelet aggregation agent.  
However, based on the pharmacological studies, the observed toxicity appeared to be worse than  
that of ticlopidine. Therefore, it was decided that PCR 1033 was not a good candidate for further  
development.  
The Enantiomers of PCR 1033: PCR 3071 and PCR 3072  
Page: 235  
[756] In 1978, Dr. Maffrand asked Mr. Badorc to separate PCR 1033 using the diastereomeric salt  
resolution. Using the diastereomeric salt resolution for the first time, a technique learned at  
Université de Rennes, Mr. Badorc was rapidly successful in his first attempt and separated the  
enantiomers of PCR 1033. He began working on June 16, 1977 and completed the work on June 17,  
1977. The levo-rotatory enantiomer was called PCR 3071 and the dextro-rotatory enantiomer was  
called PCR 3072. It was later found that PCR 3071 was less well-tolerated than ticlopidine and  
could not be administered to humans. The development of PCR 3071 therefore ceased.  
PCR 3549  
[757] Also in 1978, Mr. Badorc synthezised the ethyl analog of ticlopidine, which was called PCR  
3233. PCR 3233 was an oily base, but Mr. Badorc was able to make a crystalline nitrate salt, which  
was called PCR 3549. Dr. Maffrand asked Mr. Badorc to obtain the enantiomers for PCR 3549.  
However, Mr. Badorc failed to separate PCR 3549 using diastereomeric salt formation, which was  
the same technique used to separate PCR 1033. Mr. Badorc decided to try another technique called  
asymmetric synthesis. Two enantiomers (PCR 3620 and PCR 3621) were obtained from PCR 3549  
using asymmetric synthesis.  
[758] Based on an apparently favourable activity/toxicity ratio, Dr. Maffrand formed the view that  
PCR 3549 should be developed as a drug candidate. However, given toxicity issues in animals and  
lack of sufficient therapeutic activity, the development of PCR 3549 was abandoned.  
Page: 236  
Resolution of PCR 4099  
[759] Mr. Badorc stated that Dr. Maffrand made the decision – perhaps with Sanofi’s Research  
division – to separate the enantiomers of PCR 4099. In all there were three (3) attempts to resolve  
PCR 4099.  
[760] First, Mr. Badorc and Dr. Fréhel decided that an asymmetric synthesis similar to the one  
used to obtain the enantiomers of PCR 3549 would have a greater chance of success for PCR 4099  
than trying to separate the enantiomers via diastereomeric salt resolution as experienced with PCR  
1033. Mr. Badorc indicated that this choice was preferred for fear of racemization (Badorc, T3936-  
3940). However, the Court observes that in a report dated June 12th, 1986 (PCR 4099 Resolution of  
R and S Enantiomers of PCR 4099) (P-161), authored by Mr. Badorc and Dr. Fréhel, there is no  
mention of any concern of racemization in using the diastereomeric salt method. Further, there is  
also no mention of racemization in Mr. Badorc’s Canadian affidavit of June 2003 in the part  
describing the separation of PCR 4099.  
[761] In any event, the asymmetric synthesis route was chosen instead of the diastereomeric salt  
resolution. Mr. Badorc decided to synthesize only one enantiomer of an intermediate called  
OCBATH (cyclization instead of resolution) by starting with an enantiomerically pure precursor  
molecule and then converting that intermediate into one of the enantiomers of PCR 4099 according  
to the following alkylation reaction:  
Page: 237  
CO2CH3  
CO2CH3  
HN  
N
(CH2O)n  
AcOH  
S
S
Cl  
Cl  
Dextro-rotatory or  
Levo-rotatory enantiomer  
of PCR 4099  
Dextro-rotatory or  
Levo-rotatory enantiomer  
of OCBATH  
[762] On November 12, 1985, Mr. Badorc first synthesized the dextro-rotatory enantiomer of  
methyl-2-chlorophenyl-glycinate. He then synthesized the levo-rotatory enantiomer. Both syntheses  
were done according to the following condensation reaction scheme:  
CO2H  
CO2CH3  
NH2  
NH2  
SOCl2  
CH3OH  
Cl  
Cl  
[763] This enantiomerically pure product was then used in the following reaction:  
CO2CH3  
CO2CH3  
O
O
S
O
H2N  
HN  
∆
+
CH3CN  
S
S
Cl  
Cl  
[764] These experiments yielded the OCBATH compound. However, analytical results indicated  
that the alkylation reaction had led to a racemization, giving Mr. Badorc the racemic OCBATH  
compound instead of the single enantiomers he was seeking. This route to synthesis was therefore  
abandoned.  
Page: 238  
[765] Secondly, Mr. Badorc decided to synthesize the PCR 4099 enantiomers by resolving the  
racemic OCBATH compound by making disatereomeric salt with a chiral acid, followed by  
fractional recrystallisation. Mr. Badorc was successful in yielding a salt from one of the enantiomers  
of the OCBATH compound. However, Mr. Badorc explained that when he tried to cyclize the  
enantiomers of the OCBATH in order to get the corresponding enantiomers of PCR 4099, he  
obtained racemic PCR 4099 in both cases. This approach was also abandoned.  
[766] Mr. Badorc then turned to a precursor of PCR 4099, PCR 3068, but the separation did not  
succeed. Mr. Badorc then reverted to PCR 4099 for a third attempt.  
[767] Having failed with two previous attempts at asymmetric synthesis on PCR 4099, Mr. Badorc  
decided to attempt a separation of the enantiomers by formation of diastereomeric salts, the same  
technique used to separate PCR 1033 which was successful for PCR 1033 but had initially been  
discarded for PCR 4099. Mr. Badorc testified that the decision to use an acid was risky, because  
acid can racemize the enantiomers (Badorc, T3950-3952). By combining acid and solvents, a gum  
formed. Mr. Badorc testified that he set up a series of tubes containing different quantities of dextro-  
rotary camphor-10-sulfonic acid with different solvents. He then sealed the tubes and he waited one  
month before any crystals formed. He then added 0.4 equivalents dextro-rotatory camphor-10-  
sulfonic acid and after 48 hours a few crystals appeared. Following further manipulations, Mr.  
Badorc was successful in obtaining the enantiomers of the PCR 4099 on April 15, 1986.  
Page: 239  
[768] The biological department tested the individual enantiomers for activity. The tests revealed  
that the dextro-rotatory enantiomer of PCR 4099 had all the activity and the levo-rotatory was  
inactive. The levo-rotatory was also shown to be more toxic that the dextro-rotatory (i.e.  
clopidogrel).  
[769] Next, Sanofi turned to the preparation of clopidogrel as a pharmaceutically acceptable salt.  
On July 3, 1987, Sanofi had three (3) salts: the camphorsulfonate, the hydrogen sulfate and the  
hydrobromide salts, each being considered for development. On August 11, 1987, Sanofi had tested  
the salts and determined that the hydrogen sulfate and camphorsulfonate salts were similar in  
physical and chemical stability and had better properties compared to the hydrobromide or the  
hydrochloride camphorsulfonate salts.  
[770] The Court had the benefit of listening to Mr. Badorc for two (2) days. During these two (2)  
days, Mr. Badorc appeared to adjust his testimony constantly. Crucial portions of Mr. Badorc’s  
testimony remained incomplete, inconsistent and to some extent left the Court puzzled. There are a  
number of discrepancies between the story told by Mr. Badorc to the Court and the documentary  
evidence, more specifically his laboratory notebook.  
[771] The most important discrepancies that surfaced at trial are found in Mr. Badorc’s laboratory  
notebook relating to the test tubes screens (otherwise known as the chemist’s “secret garden”).  
Page: 240  
Test Tubes  
[772] Mr Badorc’s laboratory notebook relates that on March 4, 1986, one equivalent of  
camphorsulfonic acid was added to PCR 4099 in ethanol. A gum was obtained in the experiment  
but no crystals were formed (Badorc, T4115). On March 18, 1986, 0.4 equivalent of  
camphorsulfonic acid was added to PCR 4099 in acetone and on March 21, 1986 crystals were  
obtained, which is confirmed by the entry for March 24, 1986 (Badorc, T4135).  
[773] Mr. Badorc testified that he conducted a series of test tube screens. The problem with Mr.  
Badorc’s testimony is that these test tubes screens were not recorded in his laboratory notebook and  
were not provided to the Court in any other documents. The test tubes screens are key to the  
difficulty of the work as alleged by Mr. Badorc, but his testimony in this regard was unpersuasive.  
[774] Mr. Badorc told the Court that the reason for not recording the failed test tube experiments  
in his notebook is because he was ultimately successful. Mr. Badorc said that his laboratory  
notebook was the successful experiment. He also provided a peculiar reason in support of failing to  
enter the test tube screens in the laboratory notebook: the chemist’s “secret garden” (Badorc,  
T4117). By virtue of this concept, the chemist would be exempt from recording failed attempts. Yet,  
in other instances, the laboratory notebook contains records of unsuccessful attempts at  
diastereomeric salt formation for PCR 4099. Mr. Badorc’s explanation for not recording his  
experiments because they were failures when there was ultimately a successful experiment is thus  
unconvincing. It is contradicted by the fact that he recorded his March 4, 1986 experiment which  
was a failure. It is also contradicted by the fact that the failure with tartaric acid that was recorded  
for the attempted separation of PCR 3549 before recording the failures with other acids. In sum, Mr.  
Page: 241  
Badorc seemed to have varying subjective standards in terms of the experiments that would  
eventually find their way in his notebook. His explanation regarding these inconsistencies failed to  
convince the Court.  
[775] Finally, it is noted as an obiter that Mr. Badorc’s U.S. deposition makes no mention of the  
test tube trials and Mr. Badorc’s evidence at trial was that these experiments started in February  
1986. However, his evidence before the Canadian court in the NOC case, which was repeated in his  
Australian affidavit, was to the effect that these experiments were attempted in March 1986. This is  
a further discrepancy that weakens Mr. Badorc’s credibility as a witness in this case.  
[776] The Court also agrees with Apotex that Mr. Badorc’s crystal clear recollection of  
unrecorded test tube trials, with precision as to the resolving agents, their amounts and the solvents,  
stands in stark contrast to Mr. Badorc’s failed memory with respect to the attempted separation of  
PCR 3549. Unlike the test tube trials for PCR 4099, the separation work in the case of PCR 3549  
was recorded in Mr. Badorc’s laboratory notebook. Nonetheless, in 2003, under oath, Mr. Badorc  
had simply forgotten that he had attempted separation by diastereomeric salts and had successfully  
separated the enantiomers by asymmetric synthesis. He forgot the separation of PCR 3549,  
notwithstanding the fact that it was the first time that he had ever carried out an asymmetrical  
synthesis of an enantiomer. The Court does not accept that these discrepancies are trivial. Rather,  
they relate to a number of material points at issue in this case.  
[777] Mr. Badorc also mentioned that he seeded the March 18, 1986 experiment with crystals  
from the second of the two screens. Again, this was not recorded in his laboratory notebook for the  
Page: 242  
March 18 experiments. Had it been recorded, it could possibly have corroborated the existence of  
the test tube experiments.  
[778] There is also an issue with respect to the time dedicated to separating the enantiomers of  
PCR 4099. Mr. Badorc testified that it occupied the majority of his time during five (5) months. He  
also testified that he waited one month – mid-February to mid-March 1986 – before obtaining the  
first crystals. The computation of Mr. Badorc‘s fifty-five (55) days of work apart from the test tube  
screens are not listed in the laboratory notebook or on another list. There is no list of page numbers  
from the laboratory notebook in evidence allowing the Court to compute the fifty-five (55) days of  
work alleged by Mr. Badorc. The approximate and vague explanation provided by Mr. Badorc in  
this regard was unconvincing.  
[779] Mr. Badorc also confirmed that he used camphorsulfonic acids which were taught by the  
work of Jacques and Collet and were commercially available acids. At the time Mr. Badorc  
performed the separation of PCR 4099, he believed that camphorsulfonic acid was the strongest  
acid:  
Q. Thank you. We talked about some of the chiral acids yesterday, and I  
think you mentioned also Jacques and Collet yesterday in your evidence.  
Am I right that at the time you were going to separate 4099, there was a  
list of optically active acids that was available, a list of commercial  
products?  
R. Oui, oui, dans tous les catalogues qui peuvent exister, Aldrich, Sigma, j’en  
passe, il y a la liste d’acides chiraux commercialement disponibles.  
Q. Okay. And of that list, would you say perhaps there were about a dozen  
optically active acids that would have been available to you?  
R. Je dirais, à l’époque, peut être bien à l’époque oui, même peut être plus ou  
peut être moins, je sais pas.  
Q. Okay.  
R. Mais il y avait des acides chiraux disponibles commercialement, qu’on  
voyait dans tous les catalogues, disponibles dans tous les laboratoires.  
Page: 243  
Q. Okay. And would I be correct that of those that were available to you, the  
strongest at the time that you were doing the separation was  
camphorsulfonic acid?  
R. Non.  
Q. Do you still have - I told you to put it away, so I’m sorry, but document  
number 7, the US trial, I would like you to go to page 1817. I would like  
you to go - do you have it, 1817? I think you have it, because it looks like  
you are reading. 1817, I would like you to go to line 11. You were asked  
the question by the Court on that occasion:  
“What is the universe that you start with of optically-active acids? How  
many are in this list or lists that you are referring to?”  
You say at line 14:  
“I would say that perhaps there are about a dozen optically active  
acids, and the strongest being - now, I'm talking about the  
strongest at the time that we were doing this, was camphorsulfonic  
acid.”[As read]  
Were you asked that question by the Court and did you give that answer  
to the Court on February 7th, 2007 in the US trial?  
R. C’est la réponse que j'ai donnée au tribunal, oui, parce que je pensais,  
j’avais mis l’acide toluyl tartrique et dibenzoyl tartrique dans la série de  
tubes, et c’est vrai que je pensais que le camphre sulfonique était le plus  
fort. Et c’est qu’après que j’aie regardé, j’ai vu de que l'acide toluyl  
tartrique, que je pensais un peu plus faible que l’acide camphre  
sulfonique, ne l’était pas. En fait, c’était le toluyl tartrique qui était le plus  
fort. Mais à l’époque où j’ai témoigné ça aux États Unis, je pensais que  
l’acide camphre sulfonique, oui, était plus fort que l’acide dibenzoyl  
tartrique. Et j’ai contrôlé après, et c’est en fait, l'inverse. C’est le toluyl  
tartrique qui est plus fort, après le dibenzoyl tartrique et après l’acide  
camphre sulfonique.  
Q. So after the trial, you learned or discovered that the camphorsulfonic acid  
was not the strongest acid. You learned that after the trial; correct?  
R. Après le procès, oui. Je savais que les autres étaient des acides forts, mais  
je pensais que l’acide camphre sulfonique, innocemment, était plus fort  
que l’acide dibenzoyl tartrique. J’étais un peu surpris, mais en fait, le plus  
fort, c’est le dibenzoyl tartrique.  
Q. So up until the trial, your belief that the camphorsulfonic acid was the  
strongest acid, then, because that is the answer you gave to the Court?  
R. Je le pensais, oui, je savais que les autres étaient des acides forts, mais je  
pensais que l’acide camphre sulfonique était plus fort.  
Q. When you did the separation of 4099, your belief was that the  
camphorsulfonic acid was the strongest acid; correct?  
R. C’est exact.  
(Badorc, cross T4177-4181)  
[Emphasis added]  
Page: 244  
Q. Thank you. We talked about some of the chiral acids yesterday, and I  
think you mentioned also Jacques and Collet yesterday in your evidence.  
Am I right that at the time you were going to separate 4099, there was a  
list of optically active acids that was available, a list of commercial  
products?  
R. Yes. In all the catalogues which can exist, there is – there is a list of chiral  
– commercially available chiral acids.  
Q. Okay. And of that list, would you say perhaps there were about a dozen  
optically active acids that would have been available to you?  
R. At the time, I’d say perhaps even more or even less. I wouldn’t know.  
Q. Okay.  
R. There were chiral acids which were commercially available, which we  
could see in all of the catalogues, which were available in all labs.  
Q. Okay. And would I be correct that of those that were available to you, the  
strongest at the time that you were doing the separation was  
camphorsulfonic acid?  
R. No.  
Q. Do you still have - I told you to put it away, so I’m sorry, but document  
number 7, the US trial, I would like you to go to page 1817. I would like  
you to go - do you have it, 1817? I think you have it, because it looks like  
you are reading. 1817, I would like you to go to line 11. You were asked  
the question by the Court on that occasion:  
“What is the universe that you start with of optically-active acids?  
How many are in this list or lists that you are referring to?”  
You say at line 14:  
“I would say that perhaps there are about a dozen optically-active  
acids, and the strongest being - now, I’m talking about the  
strongest at the time that we were doing this, was camphorsulfonic  
acid.” [As read]  
Were you asked that question by the Court and did you give that answer  
to the Court on February 7th, 2007 in the US trial?  
R. That is the question I gave the Court, because I thought I had to put  
ticlopidine acid in the series of tubes, and it is true that I thought that  
camphorsulfonic was the strongest. And it is only after I looked at it that I  
noticed that the tartaric acid, which I thought weaker than  
camphorsulfonic, was not so. In fact, it was toluoyl tartaric which was the  
strongest. But at the time when I testified in the United States, I thought  
that the camphorsulfonic acid, yes, was stronger than the dibenzoyl  
tartaric acid in a control afterwards, and it was in fact toluoyl (ph.) tartaric  
acid was the strongest and, after, camphorsulfonic acid.  
Q. So after the trial, you learned or discovered that the camphorsulfonic acid  
was not the strongest acid. You learned that after the trial; correct?  
R. After the trial, yes. I know that the other was strong acid, but I thought  
that camphorsulfonic acid was stronger than the dibenzoyl (inaudible)  
tartaric acid, and I was surprised but in fact the strongest is the dibenzoyl  
tartaric acid.  
Page: 245  
Q. So up until the trial, your belief that the camphorsulfonic acid was the  
strongest acid, then, because that is the answer you gave to the Court?  
R. Yes, I thought so. I thought the camphorsulfonic was stronger.  
Q. When you did the separation of 4099, your belief was that the  
camphorsulfonic acid was the strongest acid; correct?  
R. That is correct.  
(Badorc, English RD7532)  
[Emphasis added]  
[780] The Court observes that Mr. Badorc’s recollection regarding the solvents used changed and  
seemed to improve between this case and previous cases. For instance, Mr. Badorc indicated that he  
used acetone and ethyl alcohol with the acids at trial, whereas he could not provide an answer in this  
regard in an earlier case (Badorc, T4035).  
[781] Also, it is noteworthy that Mr. Badorc decided to conduct his work on PCR 4099 using the  
asymmetrical synthesis route instead of the diastereomeric salt resolution. This decision stems from  
the fact that the diastereomeric salt resolution that proved to be successful with PCR 1033 proved to  
be unsuccessful with PCR 3549. This led Mr. Badorc to take a “detour” and spend time trying to  
separate PCR 4099 using the asymmetric synthesis technique. This is a detour that the POSITA  
would not have taken.  
[782] When Mr. Badorc eventually reverted to the diastereomeric salt resolution technique, he was  
successful in separating the enantiomers of PCR 4099. The separation of PCR 1033, PCR 3549 and  
eventually PCR 4099 can in fact be viewed in a continuum. The bulk of the time that Mr. Badorc  
spent on PCR 4099 seemed to be in respect of his attempted asymmetrical synthesis. Indeed, Mr.  
Badorc took that avenue of diastereomeric salt resolution in performing the separation on PCR 1033  
Page: 246  
with no failed steps (Badorc, T4014). As noted, it is the work on PCR 3549 performed by Mr.  
Badorc that led him to take a “detour” in using the asymmetrical synthesis technique. However after  
two (2) attempts using the assymetrical synthesis, he eventually reverted to the diastereomeric salt  
resolution technique he had used in successfully separating PCR 1033 and was in turn successful in  
separating the enantiomers of PCR 4099. A person of ordinary skill in the art would not be led from  
the outset to attempt asymmetrical synthesis to obtain the enantiomers of PCR 4099. Hence, on the  
evidence of this record, the Court finds that the actual course of conduct performed by Mr. Badorc  
revealed no substantial difficulty.  
(5) Conclusion on Obviousness  
[783] In sum, the Court finds that the PCR 4099 compound, albeit not its properties, was part of  
the common general knowledge and was featured in the ‘875 genius Patent; the POSITA would  
have been directed towards the classic Pasteur method; the relevant solvants most commonly used  
in diastereomeric salt resolution (Pasteur method) were known; the selection of salts was a well-  
known established methodology at the relevant time; there was a motivation to separate the  
enantiomers of PCR 4099 at the relevant date.  
[784] In weighing all of the factors on a balance of probabilities, the Court concludes that the  
invention in the ‘777 Patent was “obvious to try” and, therefore, the ‘777 Patent and its claims are  
invalid.  
Page: 247  
IX  
Overall Conclusions  
[785] In conclusion, Apotex’ impeachment action in Court File No. T-644-09 is accordingly  
allowed. As a consequence, Sanofi’s action in Court File No. T-933-09 is dismissed.  
[786] In summary, the Court has found that each of the claims of the ‘777 Patent are invalid for  
lack of utility. More particularly, the Court has found that the ‘777 Patent does not disclose the  
requirements for sound prediction.  
[787] Further, in the event the ‘777 Patent disclosed the requirement for sound prediction, the  
Court has found on the basis of the record before it, and on balance of probabilities, that the claims  
were obvious as of the appropriate date for obviousness.  
[788] With respect to costs, the parties will be given a period of time to attempt to resolve the issue  
of costs amongst themselves. Prothonotary Tabib has advised the Court that she would be available  
to assist the parties in settling this matter. The Court has confidence that the parties will succeed.  
[789] Should the parties be unable to agree on costs, they may serve and file written submissions  
as to costs on or before Friday, January 13, 2012. Such submissions should not exceed ten (10)  
pages. Reply submissions should not exceed five (5) pages and may be served and filed by Friday,  
January 27, 2012.  
[790] Finally, the Court reiterates its thanks to the parties’ counsel involved in this litigation for  
their professionalism, respect and courtesy vis-à-vis each other and vis-à-vis the Court.  
Page: 248  
POSTCRIPT  
[1] These Public Reasons for Judgment are a redacted version of the Confidential Reasons for  
Judgment which were issued on December 6, 2011 pursuant to the Direction dated December 6,  
2011. The parties advised the Court on December 13, 2011 that portions of the Confidential  
Reasons for Judgment should be redacted.  
“Richard Boivin”  
Judge  
Page: 1  
APPENDIX A  
List of Witnesses  
A.  
Apotex’ Expert Witnesses  
(1)  
Dr. Jack Hirsh  
Dr. Jack Hirsh is a medical doctor in clinical and research haematologist with particular  
expertise in anticoagulant, platelet and thrombosis research and therapy and in the diagnosis,  
prevention and treatment of arterial and venous thrombosis in humans.  
Dr. Hirsh gave evidence with regards to Haemostasis and Thrombosis. He gave some  
background as to how platelets function and how arterial and venous thrombosis is formed. He also  
gave evidence as to which tests were commonly used to measure platelet aggregation and/or platelet  
inhibition properties and discussed the ones used in the ‘777 Patent. Dr. Hirsh also addressed the  
issue of animal models, species differences and extrapolation from animals to humans. Finally,  
Dr. Hirsh gave evidence about the PCR 4099 abstracts.  
(2)  
Dr. James E. Sanders  
Dr. James Sanders is a toxicologist specialized in veterinary toxicology, toxicological and  
veterinary pathology, safety, pharmacology, and risk assessment. He has particular expertise in the  
application of the knowledge from these fields to the design, conduct, assessment and conclusions  
that may be drawn from animal or human studies as predictors of human toxicological responses in  
the context of the development of pharmaceuticals for human use, regulatory requirements in  
Page: 2  
respect of the provision of toxicological information for pharmaceuticals intended for human use  
and the presentation of toxicological data to the FDA, including IND submissions.  
Dr. Sanders gave evidence with regards to toxicology. He provided some background about  
the principles of ADME, the LD50 tests, the ED50 tests and the calculation of the therapeutic index.  
He also addressed the issue of the toxicity studies done for PCR 4099, those for the ‘875 Patent as  
well as those in Table IV of the ‘777 Patent. He also provided evidence on human testing and the  
extrapolation of toxicity data from rats to humans.  
(3)  
Dr. Irving Wainer  
Dr. Irving Wainer is an expert in medicinal chemistry and the stereospecific pharmacology  
of chiral drugs, including their stereochemical and pharmacological properties, synthesis and  
resolutions thereof, and their metabolic and pharmacologic behaviour. Dr. Wainer is also an expert  
in regulatory requirement and practices of pharmaceutical companies regarding racemic drugs and  
their enantiomers, their development and submissions to regulatory authorities.  
Dr. Wainer gave evidence with regards to chemistry and chiral compounds. He provided a  
background on the history of chiral chromatography (HPLC) and explained the techniques used to  
separate enantiomers. More particularly, he addressed the issue of the Pirkle column, the ADG  
column and the Cyclodextrin column. Dr. Wainer explained the difference between chiral medicine  
and chiral property. He also provided background about the regulatory reasons to separate  
enantiomers (the 1992 FDA policy).  
Page: 3  
(4)  
Dr. Brian M. Adger  
Dr. Brian Adger is an expert in pharmaceutical chemistry, including the synthesis of chiral  
pharmaceutical molecules, the formation of salts of pharmaceutical molecules, the resolution of  
antimeric pharmaceutical molecules from racemic mixtures, and the direct synthesis of enantiomeric  
pharmaceutical molecules and the chemical development of new drugs in the pharmaceutical  
industry, including the development of new chiral drugs and single enantiomer drugs.  
Dr. Adger gave evidence on the isolation of single enantiomers. He addressed the issues of  
diasteriomeric resolution as well as asymmetric synthesis.  
(5)  
Dr. Rene H. Levy  
Dr. Rene Levy is an expert in pharmacology with particular expertise in the  
biopharmaceutics, metabolism, disposition, pharmacokinetics and pharmacodynamics of drug  
products and their metabolites.  
Dr. Levy provided evidence on pharmacodynamics and the kinetics of racemic drugs. He  
addressed the issues of metabolites (secondary and tertiary) and their roles in the metabolism. More  
particularly, he addressed the issue of interspecies differences with regards to metabolism. Finally,  
he gave evidence on double blind human studies.  
The Court also recognized that Dr. Levy had experience in chiral molecules including how  
pharmacological responses in these areas vary in different animal species, including humans.  
Page: 4  
B.  
Apotex’ Fact Witnesses  
(1)  
Donald John Barber  
Mr. Donald Barber is currently the Formulation Development New Products Manager at  
Apotex Inc. Mr. Barber worked for Apotex Inc. in the formulation development group throughout  
the relevant period.  
Mr. Barber gave evidence about the nature of the work entailed in developing dosage  
formulations, including the nature of the work involved in first evaluating and determining the  
relevant physico-chemical characteristics of the active ingredient, and the various steps involved in  
the pre-formulation and formulation development process, and the preparation and evaluation of  
those batches of the final dosage form submitted for approval to regulatory authorities.  
(2)  
Galina Ayyoubi  
Ms. Galina Ayyoubi is the Quality Assurance Manager of process manufacturing at Apotex  
Inc. Ms. Ayyoubi is responsible for developing and implementing the quality control protocols and  
procedures governing the use and handling of material involved in the preparation of  
pharmaceutical products.  
Ms. Ayyoubi gave evidence about the nature of Apotex’ quality control procedures and  
protocols, and their implementation with respect to the receipt and use of clopidogrel and  
clopidogrel salts.  
Page: 5  
(3)  
John Hems  
Mr. John Hems was formerly the Director of Regulatory Intelligence at Apotex Inc. Mr.  
Hems was employed by Apotex Inc. in the regulatory affairs group throughout the relevant period.  
Mr. Hems gave evidence regarding the development of the Apo-clopidogrel regulatory  
submissions. He identified the information required to be contained in regulatory submissions,  
including those relating to clopidogrel. He also gave evidence concerning the characteristics and  
properties of the active ingredient used in dosage formulations, and the dosage formulations  
themselves, and identified those extracts from Apotex’ regulatory submissions that related to  
Apotex’ use of clopidogrel for these purposes. He also gave evidence regarding the limitations  
issue.  
(4)  
Jose Miguel Lazcano Seres  
Mr. Miguel Lazcano Seres is the Technical Director of […] .  
Mr. Seres gave evidence about the method used to manufacture the clopidogrel sold to  
Apotex.  
(5)  
Edson Sanchez  
Mr. Edson Sanchez is the Plant Manager of […] .  
Mr. Sanchez gave evidence about the method used to manufacture the clopidogrel sold to  
Apotex.  
Page: 6  
(6)  
Antoniette Walkom  
Ms. Antoniette Walkom is the Vice-President of the Quality Assurance and Regulatory  
Affairs, Apotex Pharmachem. Ms. Walkom gave evidence about Apotex Pharmachem’s operations  
generally and, in particular, its research and development activities with respect to clopidogrel,  
including its regulatory filings.  
(7)  
Dr. Bernard Sherman  
Dr. Bernard Sherman is the Chair of Apotex Inc.  
Dr. Sherman gave evidence about the corporate organization and history of the Apotex  
companies, the supply of active pharmaceutical ingredients, including clopidogrel and the  
development of Apo-clopidogrel.  
Dr. Sherman also explained the Canadian litigation relating to Apo-clopidogrel, the sale of  
Apo-clopidogrel, including the terms of trade relating to same, the U.S. litigation relating to Apo-  
clopidogrel, the circumstances surrounding entry into the March and May 2006 Settlement  
Agreements, the limitations issue and the issue of experimental use.  
(8)  
Dr. Robert W. Colman  
Dr. Robert Colman is a professor emeritus at Temple University.  
Dr. Colman described what occurred at the Xth International Congress on Thrombosis and  
Haemostasis and the Joint Congress of the International Society of Thrombosis and Haemostasis.  
Page: 7  
He also described his knowledge of the abstracts and posters presented at these conferences and  
their publication.  
(9)  
Gordon Eli Fahner  
Mr. Gordon Fahner is currently the Vice President of Supply Chain at Apotex Inc. Mr.  
Fahner has been employed at Apotex in progressively senior positions in the accounting area.  
Mr. Fahner was thoroughly familiar with the internal systems and procedures used at  
Apotex to record and track the receipt and subsequent use of the materials used in developing  
dosage formulations and implementing Apotex’ manufacturing processes.  
Mr. Fahner gave evidence relating to the quantities of clopidogrel that were used by Apotex  
for all experimental and regulatory purposes, and how those quantities were calculated.  
Mr. Fahner also addressed the corporate organization of the Apotex companies, the supply  
of active pharmaceutical ingredients, including clopidogrel, the supply and usage of excipients,  
including those related to Apo-clopidogrel, the development of Apo-clopidogrel. He also explained  
the sale of Apo-clopidogrel, including the terms of trade relating to same, the U.S. litigation relating  
to Apo-clopidogrel, the limitations issue and the issue of experimental use.  
Page: 8  
C.  
Sanofi’s Expert Witnesses  
(1)  
Dr. Stephen Byrn has expertise in medicinal, organic and solid state chemistry with  
experience in stereochemistry and chiral compounds, with experience in the use and  
Dr. Stephen R. Byrn  
characterization of pharmaceutical salts which include formulation of drug products, including the  
advantage of avoiding hygroscopicity, water solubility and crystallinity, and some experience in the  
accessibility of scientific literature in the mid to late 1980s.  
Dr. Byrn provided evidence on the different methods to separate enantiomers. Regarding  
separation, he responded to Dr. Wainer’s evidence. Dr. Byrn addressed the issue of salts. More  
particularly, he discussed the lists of salts, the properties of salts and the screening of salts. He also  
provided evidence to compare Apotex’ process to make clopidogrel with Sanofi’s process (Claim 6  
of the ‘777 Patent).  
(2)  
Dr. Joseph V. Rodricks  
Dr. Joseph Rodricks is a toxicologist with experience in the use of toxicological data in  
safety and risk assessment, the ability to extrapolate from animal data, and experience with  
regulatory and drug approval process.  
Dr. Rodricks provided evidence with regards to toxicology. He responded to Dr. Sanders’  
evidence. Dr. Rodricks discussed pre-clinical testing as well as adverse effects of drugs. He also  
discussed Sanofi’s internal studies on toxicology for the ‘777 Patent.  
Page: 9  
(3)  
Dr. Stephen G. Davies  
Dr. Stephen Davies is an expert in medicine and organic chemistry medicinal and organic  
chemist, with experience in stereochemistry and chiral compounds, the methodologies used to  
obtain individual enantiomers, the biological impact of chiral differences. He also has experience in  
the accessibility of scientific literature in the mid to late 1980s and some experience with whether  
there were regulatory policies in the late 1980s with respect to drugs that have a chiral centre.  
Dr. Davies gave evidence with regards to the separation of enantiomers. More particularly,  
he held that it was not an easy task and that it had to be done “from scratch”. He gave evidence  
about the motivation to separate and a brief background as to the growing interest in enantiomers.  
He also provided evidence about PCR 4099. Finally, he discussed the properties of compounds and  
the importance of their quantity.  
(4)  
Dr. Ronald J. Shebuski, SR  
Dr. Ronald Shebuski is qualified as a cardiovascular pharmacologist with experience in  
hemostasis and thrombosis, the pharmacology and development of antithrombotic and antiplatelet  
agents, in vivo, in vitro, and ex vivo techniques used to assess the biological activity of antiplatelet  
and antithrombotic agents, the ability to extrapolate based on the results from these techniques and  
some experience in the accessibility of scientific literature in the mid to late 1980’s.  
Dr. Shebuski gave evidence on haematology. He responded to Dr. Hirsh’s evidence. More  
particularly, he discussed the issues of metabolites and human extrapolation. He addressed the issue  
Page: 10  
of the metabolites and their role in this instance. Finally, he gave his opinion on the sound prediction  
of the ‘777 Patent.  
D.  
Sanofi’s Fact Witnesses  
(1)  
Dr. Thierry Saugier  
Dr. Thierry Saugier is the Vice-President, Alliance and Partnership at Sanofi-Aventis.  
Dr. Saugier described the organization of the plaintiff, Bristol-Myers Squibb, Sanofi  
Pharmaceuticals Holding Partnership (the “Partnership”) and its role in the marketing of Plavix®  
(clopidogrel bisulfate). Dr. Saugier also discussed agreements relating to the licensing of intellectual  
property rights, including Canadian Patent 1,336,777, by Sanofi-Aventis to the Partnership.  
(2)  
Dr. Judith Lynn Weissinger  
Dr. Judith Weissinger is the President and CEO of Weissinger Solutions Inc.  
Dr. Weissinger gave evidence concerning the approach adopted by the U.S. Food & Drug  
Administration (FDA) to the approval of racemates in the mid-1980s to the early 1990s. Dr.  
Weissinger also gave evidence on her experiences as Chair of the Center for Drug Evaluation and  
Research Stereoisomers Committee.  
Page: 11  
(3)  
Dr. Frédéric Lacheretz  
Dr. Frédéric Lacheretz is a toxicologist and doctor in Veterinary Medicine. He joined  
Sanofi-Aventis (or its predecessors) in around 1983 and remained at Sanofi-Aventis for over twenty  
years. As Head of Toxicological Laboratory Studies at the relevant time, Dr. Lacheretz was  
involved in and supervised toxicological studies in respect of thienopyridine compounds, in  
particular PCR 4099 and clopidogrel, conducted in the 1980s by Sanofi-Aventis.  
(4)  
Mr. Alain Badorc  
Mr. Alain Badorc is a retired chemist at Sanofi-Aventis. He is one of the named inventors of  
Canadian Patent No. 1,336,777 (the ‘777 Patent). Prior to his retirement, Mr. Badorc was the  
laboratory executive of the laboratory in the Thrombosis and Angiogenesis Department of Sanofi-  
Aventis, Toulouse, France. He provided evidence of his work on thienopyridines.  
(5)  
Dr. Jean-Pierre Maffrand  
Dr. Jean-Pierre Maffrand is a retired scientist and former senior executive at Sanofi-Aventis.  
He supervised the inventors of Canadian Patent No. 1,336,777 (‘777 Patent), Mr. Alain Badorc and  
Dr. Daniel Fréhel. Prior to retirement, Dr. Maffrand was the Senior Vice-President, Director of  
Discovery Research at Sanofi-Aventis, Toulouse, France.  
Dr. Maffrand gave evidence on the research he conducted and/or supervised on  
thienopyridines and in particular the following compounds: PCR 1033, PCR 3549, PCR 4099,  
clopidogrel, levo-rotatory enantiomer, ‘875 compounds. Dr. Maffrand also gave evidence about the  
development of PCR 4099, the separation of PCR 4099 into its enantiomers, the activity tests  
Page: 12  
performed on clopidogrel, the levo-rotatory enantiomer and PCR 4099, the decision to discontinue  
the development of PCR 4099 and the results of the clopidogrel Phase I clinical trials in healthy  
human volunteers.  
Page: 1  
APPENDIX B  
EXHIBIT 22  
Page: 2  
Page: 3  
Page: 4  
Page: 5  
Page: 6  
Page: 7  
Page: 1  
APPENDIX C  
DATE  
1972  
EVENT  
Ticlopidine synthesized  
PCR 1033 synthesized  
1975  
1978  
Ticlopidine arrived on the French market  
June 16, 1977  
Resolution of enantiomers of PCR 1033 – PRC 3071,  
PCR 3072  
September 1978  
November 1978  
March 1979  
PCR 3071 and PCR 3072 tested for activity and toxicity  
PCR 3233 synthesized  
PCR 3549 synthesized  
March 1979  
Successful resolution of PCR 3549 intermediates to be  
used in asymmetric synthesis  
April 1979  
May 1979  
Enantiomers of PCR 3233 (3549) obtained - PCR 3620,  
PCR 3621  
PCR 3620 and PCR 3621 tested for activity and toxicity  
PCR 4099 synthesized  
July 1980  
March 1983 –  
April 1987  
Baboon convulsions reported for PCR 4099 (12-month  
toxicity study)  
July 8, 1983  
End of 1983 –  
April 1987  
Filing date ‘875 Patent application  
PCR 4099, Studies in humans  
1985  
Japanese guideline re separation of enantiomers  
San Diego conference and Sanofi abstracts and posters  
Maffrand decision to obtain enantiomers of PCR 4099  
Badorc obtains l enantiomer of PRC 4099  
July 14-19, 1985  
November 1985  
March 21, 1986  
April 7, 1986  
April 8, 1986  
April 15, 1986  
June 1-6, 1986  
Hydrochloride salt of the L enantiomer made  
Badorc obtains D enantiomer of PRC 4099  
Hydrochloride salt of the D enantiomer made  
Jerusalem conference and Sanofi abstracts and posters  
September 29, 1986 Vallee memorandum to LeFur et al. re “Enantiomers of  
PCR 4099”, referencing “B-Health Authorities” and  
Japanese joint venture request for “separation and study of  
enantiomers”  
Page: 2  
DATE  
EVENT  
March 19, 1986  
January 1987  
Kumkumian address to the APA  
Investigator’s Brochure indicated that PCR 4099 was  
highly potent and well tolerated with a very good safety  
margin  
February 1987  
FDA guidance policy re “Guidelines for submitting  
supporting Documentation in Drug Applications For the  
Manufacture of Drug Substances”  
February 17, 1987 First French priority application for ‘777 Patent  
March 31, 1987  
Maffrand memorandum to LeFur and Simon re “My  
perception of PCR 4099 today” referencing “Health  
authorities” and Japanese joint venture  
April 16, 1987  
Simon memorandum re “Development PCR 4099”  
referencing decision to stop development of PCR 4099  
May 12, 1987  
May 18, 1987  
SR 25990C, bisulfate (hemisulfate) salt prepared  
Report on toxicity testing on PCR 4099 and hydrochloride  
salts of 25990 and 25989.  
May 20, 1987  
June, 1987  
SR 25990D, hydrobromide salt prepared  
Study Report: Research on Stable Crystalline Salts of SR  
25990  
September 14, 1987 Report on toxicity testing of salts of SR 25990  
November 6, 1987 SR 25990E, taurocholate salt prepared  
November 27, 1987 Second French priority application for ‘777 Patent  
December 1987  
Start of trial of D enantiomer in humans, ending March  
1988  
February 8, 1988  
Filing date of ‘777 Patent application  
Page: 1  
FEDERAL COURT  
SOLICITORS OF RECORD  
DOCKET:  
T-644-09  
STYLE OF CAUSE:  
Apotex Inc. v. Sanofi-Aventis  
T-933-09  
DOCKET:  
STYLE OF CAUSE:  
Sanofi-Aventis and Bristol-Myers Squibb Sanofi  
Pharmaceuticals Holdings Partnership  
v. Apotex Inc., Apotex Pharmachem Inc.  
and Signa Sa de CV  
PLACES OF HEARINGS:  
DATES OF HEARINGS:  
Toronto, Ontario  
Ottawa, Ontario  
April 18, 19, 20, 21, 2011  
April 26, 27, 28, 29, 2011  
May 3, 4, 5, 2011  
May 9, 10, 11, 2011  
May 16, 17, 18, 19, 2011  
May 24, 25, 2011  
May 30, 31, 2011  
June 1, 2011  
June 13, 14, 15, 2011  
PUBLIC REASONS FOR JUDGMENT:  
BOIVIN J.  
DATED:  
December 6, 2011  
Page: 2  
APPEARANCES:  
Harry Radomski  
Richard Naiberg  
Andrew Brodkin  
Nando De Luca  
Benjamin Hackett  
David Scrimger  
Sandon Shogilev  
Belle Van  
FOR THE PLAINTIFF  
APOTEX INC.  
Anthony G. Creber  
Cristin A. Wagner  
Marc Richard  
FOR THE DEFENDANTS  
SANOFI-AVENTIS  
Rick Dearden  
Isabel Rassch  
Livia Aumand  
SOLICITORS OF RECORD:  
Goodmans LLP  
Toronto, Ontario  
FOR THE PLAINTIFF  
Gowling Lafleur Henderson LLP  
Ottawa, Ontario  
FOR THE DEFENDANTS  


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