Date: 20170922  
Docket: T-402-16  
Citation: 2017 FC 774  
Ottawa, Ontario, September 22, 2017  
PRESENT: The Honourable Mr. Justice Brown  
BETWEEN:  
PFIZER CANADA INC. and WYETH LLC  
Applicants  
and  
APOTEX INC. and  
THE MINISTER OF HEALTH  
Respondents  
PUBLIC JUDGMENT AND REASONS  
(Original and Corrected Confidential Judgment and Reasons issued August 22, 2017)  
Table of Contents  
I.  
Nature of the Matter............................................................................................................... 5  
II. Procedural Note ..................................................................................................................... 5  
III. Summary of Conclusions....................................................................................................... 6  
IV. Witnesses ............................................................................................................................... 6  
V. Facts ....................................................................................................................................... 8  
1. Background .................................................................................................................... 9  
2. The Invention Story...................................................................................................... 11  
Page: 2  
3. Invention Story in more detail: the evidence of Pfizer’s Dr. Shah............................... 16  
4. Experimentation with ODV fumarate .......................................................................... 19  
5. Attempt to form pro-drug of ODV............................................................................... 21  
6. Attempt to form an acceptable salt of ODV................................................................. 22  
7. Polymorph and crystal screening ................................................................................. 26  
8. Solubility...................................................................................................................... 27  
9. The Preparation of ODV Succinate.............................................................................. 29  
10. Permeability and bioavailability testing....................................................................... 30  
11. |||||||||||||||||||||||||||||| .................................................................................. 31  
12. Rat perfusion test.......................................................................................................... 33  
13. Beagle dog testing ........................................................................................................ 36  
14. Human testing............................................................................................................... 39  
15. Solid state forms: crystallinity, amorphous solids, polymorphs .................................. 42  
16. Polymorph screening and subcontracting polymorph screening to SSCI, Inc............. 42  
17. Dr. Aeri Park at SSCI................................................................................................... 45  
18. |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| ............................... 51  
19. Melting points and differential scanning calorimetry (DSC)....................................... 52  
20. Further temperature studies and amorphous form........................................................ 53  
21. Hygroscopicity testing (a test relevant to drug stability) ............................................. 54  
22. |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| ... 54  
23. |||||||||||||| (Crystal Form “C”) ........................................................................... 55  
24. |||||||||||||||||||||||| (Crystal Form “D”).......................................................... 56  
25. Work on other salt candidates and screens................................................................... 58  
26. Miscellaneous............................................................................................................... 59  
VI. Issues.................................................................................................................................... 59  
VII. Statutory provisions and burden of proof ............................................................................ 60  
Page: 3  
VIII. Analysis................................................................................................................................ 61  
1. Relevant Dates.............................................................................................................. 61  
2. Claims Construction..................................................................................................... 62  
A. Construction of Claims 8 and 9 ............................................................................... 72  
B. Construction of Claim 33 ........................................................................................ 80  
C. Construction of Claims 43 and 44 ........................................................................... 81  
3. Non-infringement ......................................................................................................... 82  
4. Obviousness.................................................................................................................. 85  
A. Introductory comments and summary ..................................................................... 85  
B. Legal principles in the obviousness inquiry and the Sanofi decision...................... 87  
C. Federal Court of Appeal jurisprudence including Atazanavir and Beloit ............... 98  
D. Analysis of Obviousness ....................................................................................... 104  
1. (a) Identify the notional “person skilled in the art........................................... 104  
1. (b) Identify the relevant common general knowledge of the Skilled Person..... 105  
2.  
Identify the inventive concept of the claim in question or if that cannot readily  
be done, construe it ................................................................................................ 121  
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................................................................................................................ 126  
i. Claims 8 and 9.............................................................................................. 126  
ii. Claim 33....................................................................................................... 127  
iii.Claim 43 and 44 ........................................................................................... 127  
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? ............................................... 129  
5.  
6.  
Apply the definition of obvious before Sanofi............................................. 129  
Consider the doctrine of obvious to try........................................................ 132  
Page: 4  
7.  
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?.................................................................................................................... 135  
8.  
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? ............................. 148  
9.  
Is there a motive provided in the prior art to find the solution the patent  
addresses? .............................................................................................................. 150  
10. What is the course of conduct which was followed which culminated in the  
making of the invention? ....................................................................................... 152  
11. Conclusion on obvious to try regarding Claims 8 and 9.............................. 154  
12. Conclusion on obvious to try regarding Claims 33, 43 and 44.................... 155  
13. Consideration of the guidance for obvious to try analysis set out in Sanofi 155  
14. Conclusion on obviousness.......................................................................... 156  
5. Inutility....................................................................................................................... 156  
A. Are the subject matters of Claims 33, 43 and 44 useful - are they capable of a  
practical purpose (i.e. an actual result)?..................................................................... 163  
B. Conclusion on inutility .......................................................................................... 165  
6. Overpromising in relation to subsection 27(3) of the Patent Act............................... 165  
7. Anticipation................................................................................................................ 173  
8. Double patenting ........................................................................................................ 187  
IX. Conclusions........................................................................................................................ 194  
X. Costs................................................................................................................................... 194  
XI. Confidential Reasons ......................................................................................................... 194  
***  
Page: 5  
I.  
Nature of the Matter  
[1]  
This is an application for an order pursuant to s 6 of the Patented Medicines (Notice of  
Compliance) Regulations, SOR/1993-133 as amended, SOR/1998-166, SOR/1999-379,  
SOR/2006-242 [NOC Regulations] prohibiting the Minister of Health from issuing a Notice of  
Compliance [NOC] in respect of a Notice of Allegation [NOA] sent by Apotex Inc., [Apotex] to  
Pfizer Canada Inc., previously Wyeth LLC [Pfizer or Wyeth], dated January 21, 2016, in respect  
of Canadian Patent No. 2,436,668 [668 Patent]. The 668 Patent covers the drug PRISTIQ which  
is used for the treatment of depression.  
[2]  
At issue are claims 8, 9, 33, 43 and 44. While Apotex advanced other grounds in its NOA  
and memorandum, some were subsequently abandoned such that now Apotex alleges the 668  
Patent is invalid on the grounds of obviousness, inutility, non-infringement, anticipation and  
double patenting.  
II.  
Procedural Note  
[3]  
As a procedural note, this case was argued after I heard argument in Pfizer Canada Inc  
and Wyeth LLC v Teva Canada Limited and The Minister of Health, in respect of which I  
delivered reasons and judgment in 2017 FC 777. These two cases involve different NOAs filed  
by different second persons, against the same first persons in respect of the same 688 Patent.  
While the invention story in both is essentially the same, the grounds of alleged invalidity differ.  
   
Page: 6  
The arguments were similar in some respects and differed in others; therefore there is repetition  
as between these two sets of reasons. The law is the same in both.  
[4]  
As guidance for those reading both decisions, while obviousness and inutility are at issue  
in both decisions, Apotex also advanced allegations of non-infringement, anticipation and double  
patenting which Teva did not advance in its proceeding. Claims construction is contested in this  
proceeding, but Claims 8 and 9 were agreed upon in the Teva proceeding. Apotex also raised  
overpromising in this proceeding as a ground of invalidity arising out of subsection 27(3), which  
Teva did not advance in its proceeding.  
III.  
Summary of Conclusions  
[5]  
In the reasons that follow, I find on a balance of probabilities that Apotexs allegations of  
invalidity due to obviousness, inutility, anticipation, and double patenting, together with  
Apotexs allegation of non-infringement are not justified. I find no merit in the arguments of  
invalidity based on overpromisingcontrary to subsection 27(3) of the Patent Act. Therefore,  
Pfizer will have its Order of prohibition, together with costs on terms the parties agreed on and  
which are set out in these Reasons.  
IV.  
Witnesses  
[6]  
The parties in their pre-hearing filing provided the following information on the  
witnesses, to which I have added minimally:  
   
Page: 7  
Pfizers fact witnesses:  
Dr. Syed Shah: Syed Shah is a former employee of Wyeth (and  
subsequently Pfizer) who has held a number of different titles at  
both companies. In the late 1990s to early 2000s, he was the  
Associate Director of the Chemical and Pharmaceutical  
Development Department at Wyeth and was involved in the  
development of a suitable form of ODV for clinical research and  
commercialization. He oversaw the preclinical research conducted  
on ODV succinate (and other forms of ODV), as well as later  
clinical research on ODV succinate and Pristiq®. Dr. Shah is a  
named inventor on the 668 Patent.  
Dr. Aeri Park: A former Principal at SSCI Inc., the research  
laboratory hired by Wyeth to conduct polymorph studies on ODV  
succinate. She managed the team of scientists who conducted the  
ODV succinate work, which included identifying, analyzing, and  
generating various solid state forms of ODV succinate. Dr. Park is  
a named inventor on the 668 Patent.  
Pfizers expert witnesses:  
Dr. Syed Shah: Syed Shah is a former employee of Wyeth (and  
subsequently Pfizer) who has held a number of different titles at  
both companies. In the late 1990s to early 2000s, he was the  
Associate Director of the Chemical and Pharmaceutical  
Development Department at Wyeth and was involved in the  
development of a suitable form of ODV for clinical research and  
commercialization. He oversaw the preclinical research conducted  
on ODV succinate (and other forms of ODV), as well as later  
clinical research on ODV succinate and Pristiq®. Dr. Shah is a  
named inventor on the 668 Patent.  
Dr. James Polli: James Polli is a Professor of Industrial Pharmacy  
and Pharmaceutics at the University of Maryland School of  
Pharmacy. His main research interests are (1) maximizing oral  
bioavailability through formulation and chemical approaches, and  
(2) developing public quality standards for oral dosage forms. He  
has experience in the fields of pharmaceutics, pharmacokinetics  
and bioavailability.  
Dr. Pierre Blier, MD: Pierre Blier is a full professor in the  
Departments of Psychiatry and Cellular and Molecular Medicine at  
the University of Ottawa in Ontario, Canada. He also serves as the  
Director of the Mood Disorders Research Program at the  
Page: 8  
University of Ottawa Institute of Mental Health Research at the  
Royal Ottawa Hospital. He has experience in the fields of  
neuropharmacology and psychiatry.  
Dr. Jerry Atwood: Jerry Atwood is Chairman of the Department of  
Chemistry and CuratorsProfessor at the University of Missouri-  
Colombia. He has research and academic experience in the fields  
of supramolecular chemistry, solid-state chemistry, crystal growth,  
crystal engineering, materials testing, X-ray crystallography,  
organic chemistry, pharmaceutical chemistry, inorganic chemistry  
and polymer chemistry.  
Dr. Allen Myerson: Allan Myerson is a Professor of the Practice of  
Chemical Engineering at the Massachusetts Institute of  
Technology (MIT). He has research and academic experience in  
industrial crystallization and the crystallization of pharmaceutical  
solids.  
Apotexs expert witnesses:  
Dr. Alan Parr, Ph.D.: Dr. Alan Parr is an independent consultant  
on matters related to the biopharmaceutics of pharmaceuticals. He  
has approximately 30 years of experience working in the  
pharmaceutical industry, including with Glaxo and its successor  
companies Glaxo Wellcome and GlaxoSmithKline. Dr. Parr has  
experience in the in vivo evaluation of dosage forms,  
biopharmaceutics, pharmacokinetics, drug absorption and  
bioavailability/bioequivalence testing.  
Richard J. Bastin: Richard J. Bastin is the Director of RJB Pharma  
Consulting Ltd., a consultancy business that offers advice, support  
and training on drug developability, process development, product  
development and Chemistry Manufacturing Controls strategy to  
pharmaceutical and biotechnology companies.  
Jonathan Steed, Ph. D.: Jonathan Steed is a Professor of  
Chemistry at Durham University in the United Kingdom. His  
research focusses on crystallography, crystallization, solid state  
chemistry, coordination chemistry and intermolecular interactions  
in solids.  
Page: 9  
V.  
1.  
Facts  
Background  
[7]  
The 668 Patent concerns a drug called o-desmethyl-venlafaxine, henceforth referred to as  
ODV. ODV is a serotonin and norepinephrine reuptake inhibitor [SNRI] used for the treatment  
of depression. ODV works by simultaneously inhibiting the reuptake of both serotonin and  
norepinephrine, which are two neurotransmitters believed to be implicated in depression and  
anxiety. The specific active pharmaceutical ingredient (API) at issue in this proceeding is Form I  
ODV succinate, which is a particular crystal form of a particular salt of ODV namely ODV  
succinate. Pfizer argues and as will be seen, I have accepted that Form I ODV succinate is a  
novel composition of matter, and is the subject of Claims 8 and 9, on which Claims 33, 43 and  
44 depend.  
[8]  
ODV is an active metabolite of ODVs parent drug, venlafaxine. ODV is called a  
metabolite because ODV is produced by the body when venlafaxine is administered, that is,  
venlafaxine is chemically modified in the body to form ODV; it is ODV that is responsible for  
delivering some or all of the pharmacological effect.  
[9]  
It is common ground that ODV itself and its use to treat depression have been known for  
some time. Venlafaxine - which metabolizes into ODV - was previously patented and approved  
to treat depression. Wyeth had ODV in hand since at least 1990. Wyeth and Pfizer have  
marketed ODV, as the known metabolite of venlafaxine, under the names EFFEXOR and  
   
Page: 10  
EFFEXOR XR. EFFEXOR is the immediate release version of venlafaxine (which converts in  
the body to ODV); EFFEXOR XR is the extended or sustained release version of venlafaxine  
(which also converts in the body to ODV but at a slower rate). ODV is the API in both  
EFFEXOR and EFFEXOR XR.  
[10] Both EFFEXOR and EFFEXOR XR contain venlafaxine hydrochloride which is a salt;  
venlafaxine hydrochloride is henceforth simply referred to as venlafaxine.  
[11] ODV and pharmaceutically acceptable salt forms thereofwere known and are claimed  
in both claim 22 in US Patent No. 4,535,186 (US 186), issued in 1985, and in claim 21 of  
Canadian Patent No. 1,248,540 (CA 540), issued to a Pfizer predecessor company in 1989.  
[12] Pharmaceutically acceptable saltsas the term is used in US 186 and CA 540 are formed  
by reacting an acid together with and a base. ODV is a base; therefore, to make a salt an  
appropriate acid is required for such reaction. Both US 186 and CA 540 claim ODV succinate as  
one of 11 illustrativepharmaceutically acceptable salts, and therefore include a reference to  
reacting ODV with succinic acid.  
[13] However, there is no suggestion in either US 186 and CA 540, or elsewhere in the prior  
art, that the salt ODV succinate had ever been made before. Likewise there is no suggestion that  
any crystalline form of the salt ODV succinate had ever been known or made before. Further,  
there is no evidence or argument that the crystal Form I ODV succinate, which Wyeth alleges is  
Page: 11  
the inventive concept of Claims 8 and 9, had ever been known or made before it was made by  
Wyeth.  
[14] In addition to disclosure in the Canadian (CA 540) and American (US 186) patents just  
referred to, it is agreed that another form of ODV, namely its free base, i.e., the drug ODV itself  
as opposed to a salt or crystalline form of the drug, was disclosed in International Patent  
Publication No. WO OO/59851 (WO 851) published in October 12, 2000. WO 851 listed 26  
pharmaceutically acceptable salts, again including succinic acid. Once again however there is  
no suggestion that ODV succinate had ever been made, or that the crystalline ODV succinate had  
ever been made, or that Form I ODV succinate had ever been made before it was created in  
Wyeths laboratories.  
[15] The prior art also disclosed that venlafaxine as EFFEXOR or EFFEXOR XR and their  
metabolite ODV were useful to treat depression.  
[16] As is also well known, depression is a serious medical condition that can be and is often  
debilitating. It is not disputed that all of these drugs including Form I ODV succinate help  
patients suffering from depression to regain and live more full and functional lives.  
2.  
The Invention Story  
[17] The essence of the inventive story is not generally in dispute, although aspects of it are;  
the parties disagree on its characterization, and how the inventive story relates to the obviousness  
 
Page: 12  
and obvious to try and other principles in patent law. The inventive story is also relevant to the  
dispute over the alleged lack of utility and in other respects as well. In my view the inventive  
story warrants being set out in some detail; I will summarize it first.  
[18] The inventive story as I have found it is set out below. It is drawn generally from the  
affidavits of Dr. Shah and Dr. Park; Dr. Shah who was at Wyeth at the time and was in charge of  
commercializing ODV generally and then commercializing ODV succinate. Dr. Park was in  
charge of the polymorph screening of ODV succinate at a specialized company that performed  
polymorph screening for Wyeth, namely, SSCI, Inc. [SSCI].  
[19] I accept the evidence of Dr. Park and Dr. Shah because they were there at the time of the  
invention, and have first-hand knowledge of the matters they describe. I appreciate they are both  
named inventors on the 668 Patent, but am not in any way persuaded that this affected their  
evidence whether deposed to in their affidavits, or in cross-examination.  
[20] Wyeth, now Pfizer, had venlafaxine as one of its drugs. As such, it knew that ODV was  
the active metabolite of venlafaxine. Pfizer at first through a predecessor company and then in its  
own name marketed venlafaxine as EFFEXOR and EFFEXOR XR. EFFEXOR delivered  
venlafaxine immediately, but for many patients that meant it had to be administered several  
times a day. EFFEXOR XR, a sustained release version of EFFEXOR, could be delivered once-a  
day; it delivered a larger dose at the outset but once inside the body its release was spread over a  
prolonged period of time. EFFEXOR XR is an extended or sustained release formulation which  
Page: 13  
was better for many if not most patients, including those suffering depression, because taking a  
once-a-day pill was more convenient and led to greater compliance than taking multiple pills  
throughout the day. In addition, the sustained release form would reduce side effects by reducing  
the amount of the drug released into the body at any one time versus EFFEXOR, the immediate  
release form of venlafaxine.  
[21] Wyeths problem with venlafaxine was that while its active metabolite was ODV, there  
was no solid-state form of ODV itself that could be safely stored, formulated into a drug, and  
effectively delivered to patients. Wyeth only had venlafaxine which relied on the body to be  
metabolized or converted into ODV, which then acted as the anti-depressant in the brain.  
[22] The new ODV drug that Wyeth sought to discover required several key characteristics:  
stability, solubility, permeability and bioavailability. Permeability is the ability of a drug to  
permeate through the lining of the GI tract. Bioavailability is the ability of a drug to get into the  
bloodstream, which in the oral dose sought, involves permeating the gastrointestinal [GI] tract.  
[23] The searched-for new ODV drug had to be a stable, that is, a drug that could be stored  
safely throughout the manufacturing and distribution processes. The searched for ODV had to  
remain stable throughout these processes and also in the hands hospitals and patients over  
different ambient temperatures and humidity levels one would find in the places where it might  
be manufactured, stored, distributed, and or used.  
Page: 14  
[24] The ODV drug form Wyeth was searching for had to be able to dissolve in the  
gastrointestinal [GI] tract i.e., it had to be a drug that was soluble. It also had to be a drug that  
would cross over from the GI tract into the bloodstream where it could do its work in the bodys  
systems and in particular, in the brain, i.e., it had to be a drug that was permeable and  
bioavailable.  
[25] In addition to having stability, solubility, permeability and bioavailability, the searched  
for new ODV drug needed to have these qualities without unacceptable adverse side effects such  
as nausea and vomiting which were known issues with ODV.  
[26] In summary, over some two years - with increased activity towards the end of this period  
- experimentation and drug development was conducted, initially by Wyeth, and then by Wyeth  
together with a specialized contract laboratory, SSCI. Employees of both Wyeth and SSCI are  
named inventors on the 668 Patent.  
[27] Wyeth and SSCI eventually identified a solid crystalline form of ODV that was stable,  
soluble, permeable and bioavailable. This crystalline form is known now as Form I ODV  
succinate, and Pfizer alleges this as the inventive concept in Claims 8 and 9 of the 668 Patent. It  
is common ground that this crystalline form is a new composition of matter that was never before  
made or disclosed until it was created by Wyeth. I should note that Apotex raises invalidity  
based on anticipation therefore newness is in issue, and will be dealt with later in these Reasons.  
Page: 15  
[28] I referred to the experiments that Wyeth and SSCI conducted in which Wyeth created the  
crystalline Form I ODV succinate, and in which ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| In this connection, the experts agree it would  
have been impossible for the Skilled Person to know or predict whether ODV succinate salt  
would form as a solid, whether that solid could be formed as a crystalline compound, or what the  
properties of any hypothetical crystalline solid, let alone Form I ODV succinate would be in  
terms of stability, solubility, permeability, bioavailability and adverse effects; none of this would  
be known without doing empirical research. As will be discussed further, in my view the extent  
of research envisioned by the Skilled Person and actually required in this connection was not  
routine, but in the nature of a research program.  
[29] I wish to note that an issue in this proceeding is whether the experimentation involved  
was routine experimentation, and if so, what legal consequences flow from such a finding. This  
is because the work done by Wyeth included performing salt screening, and because the work  
done by SSCI entailed a different type of screening, known as polymorph or crystal screening.  
Pfizer and Apotex agree that in general terms both salt screens and polymorph screens were  
generally known to a person skilled in the art at the time (the Skilled Person).  
[30] Wyeth not only created the ODV succinate salt, but went further and discovered and  
created a crystalline form of that salt which has become known as the crystalline Form I ODV  
succinate. Wyeth however did not know that the crystal it created ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Wyeth with its subcontractor SSCI went further.  
Page: 16  
SSCI found another three crystalline and one amorphous forms of ODV succinate in addition to  
crystalline Form I ODV succinate created by Wyeth and relied upon by Pfizer in Claims 8 and 9  
of the 668 Patent.  
[31] ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| This discovery allowed Wyeth to develop sustained  
release oral formulations that could deliver therapeutic concentrations of ODV over a prolonged  
period of time, reduce the overall incidence of certain side effects associated with higher peak  
blood concentrations of the drug, and give patients a once daily pill instead of having to take  
multiple pills throughout the day.  
3.  
Invention Story in more detail: the evidence of Pfizers Dr. Shah  
[32] Pfizers Dr. Shah, a pharmaceutical engineer, was the lead investigator involved in  
Wyeths development of ODV for clinical research and commercialization between 1999 and  
2004. Dr. Shahs evidence was that at the outset of the course of Wyeths experimentation,  
Wyeths Discovery Group considered that ODV might be a successful drug candidate for several  
reasons. ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| For example, it  
was thought that by administering the metabolite ODV directly one could have a faster and more  
potent effect.  
 
Page: 17  
[33] In addition, it was known that individuals varied in their ability to metabolize venlafaxine  
into ODV in the liver, which would affect the effectiveness of venlafaxine. By getting rid of the  
metabolic step (in which venlafaxine is converted by the body into ODV) it was thought this  
variability could be addressed. ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
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||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
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[34] Wyeth was also interested in two further matters: 1) improving patient compliance, that  
is, improving the chances of patients actually taking their medication as prescribed, and 2) the  
need to develop a new drug with reduced side effects. One way to do this would be to develop a  
drug that could be dosed once per day, which meant developing a sustained release formulation  
of ODV.  
[35] Wyeths invention story had several components in addition to this background  
knowledge.  
[36] Initially, Wyeth worked with ODV fumarate, a known salt form of ODV, but without  
success.  
Page: 18  
[37] Wyeth also attempted to make a pro-drug of ODV, again without success.  
[38] In addition, and previously, Wyeth had also worked with a number of other salt forms of  
ODV, but without success.  
[39] Wyeth then set out to determine if it could identify a more appropriate salt form, a route  
in respect of which there was internal and science-based skepticism, a point Apotex challenged  
and which I will address shortly. Eventually Wyeth found the ODV succinate salt form, which it  
then with further research and experimentation, developed into a crystalline form then known as  
Form A, which subsequently became known as Form I ODV succinate. Having identified  
positive properties of this new crystal Form I ODV succinate in terms of solubility and stability,  
it engaged SSCI to test the crystalline Form I ODV succinate and identify and test for other  
crystalline forms; SSCI did so and identified three other crystalline forms of ODV succinate plus  
one amorphous form of ODV succinate.  
[40] Wyeth conducted studies in vivo (in the body) in mice, and in cells in vitro (outside the  
body), together with in vivo tests on rats, beagle dogs and ultimately with human volunteers.  
[41] Wyeth determined that the crystalline Form I ODV succinate had the requisite stability,  
together with solubility in addition to both suitable permeability and bioavailability. Wyeth then  
performed additional studies to develop sustained release formulations of Form I ODV succinate.  
Page: 19  
[42] The following outlines these steps in more detail.  
4.  
Experimentation with ODV fumarate  
[43] Pre-clinical work on ODV by Wyeths Discovery Group had been conducted on the  
fumarate salt form of ODV, known as ODV fumarate. ODV fumarate is formed by reacting  
ODV, which is a base, with fumaric acid to make a salt known as ODV fumarate. ODV fumarate  
is a salt form of ODV. ODV fumarate was a known salt form of ODV, which is one of the  
reasons it was looked at by Wyeth. ODV fumarate was known in the art at the time because it  
was disclosed as Example 26 of US 186 as a crystalline salt.  
[44] However, ODV fumarate had problems with bioavailability. ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
[45] This evidence indicates and I accept that oral bioavailability of ODV fumarate was  
relatively poor compared to ODV fumarate ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
|||||||||||||||||||||| The problem with the ODV fumarates bioavailability was considered by Wyeth as  
 
Page: 20  
likely due to low solubility and/or permeabilityof ODV fumarate. ||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||  
[46] As indicated previously, ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||, as Dr. Shah deposed in his affidavit, salts  
that are reasonably soluble like ODV fumarate are usually completely dissociated by the time  
they get to the GI tract. In other words, if the drug ODV became dissociated when it ceased to be  
in salt form ODV fumarate, in the GI tract, where it lacked suitable bioavailability, the same  
dissociation but poor bioavailability could obtain with the drug ODV when reacted to form other  
salts. In other words, if the dissociated drug ODV did not do well in terms of permeability when  
orally dosed as ODV fumarate, it was unclear why another salt form of ODV might behave any  
better:  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||  
Affidavit of Dr. Shah, para 22.  
[47] Apotex argues that ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
To the extent Dr. Shah refers to the views of others at Wyeth, Apotex is correct. However,  
Dr. Shah also deposed to and certainly had personal knowledge of the fact that ||||||||||||||||||||||||||||||||||||||  
Page: 21  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| , namely that since salts that are  
reasonably soluble (like ODV fumarate) are usually completely dissociated by the time they get  
to the GI tract, it was unclear how much impact a new salt would have on improving  
permeability. ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
5.  
Attempt to form pro-drug of ODV  
[48] Wyeth also attempted to develop a pro-drug of ODV in 1999-2000. A pro-drug is a  
compound which is chemically altered in the body to become its bio-active chemical form. Pro-  
drugs are also described as being created by chemically modifying the active compound to  
produce a pharmacologically inactive molecule that will be metabolized into an active form in  
the body following absorption by the body. Depending on the modifications that are made, a pro-  
drug may have improved solubility, dissolution or absorption over the active molecule.  
[49] ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
 
Page: 22  
[50] ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| In this evidence, Dr. Shah was relying on what had  
been reported to him as I agree with Apotex that he had no involvement in WyethsODV pro-  
drug development program, which it appears led to at least one successful patent application of  
which Dr. Shah was unaware.  
[51] However, I accept Dr. Shahs main evidence on this point, namely that Wyeth conducted  
pro-drug development work apart from Dr. Shahs salt and crystalline drug development work in  
connection with ODV. While Apotex calls the Wyeths attempt to find a pro-drug a diversion,  
the fact is that both parties agree that Wyeth undertook pro-drug exploration and development  
work. I accept Dr. Shahs evidence that it took place: this is not disputed by Apotexs expert  
Dr. Steed who disparaged pro-drug development regarding ODV. Accepting Apotexs argument  
that Wyeth succeeded in making and even patenting a pro-drug does not establish that pro-drug  
development was irrational or unreasonable; in my view, it proves the opposite and justifies pro-  
drug development work that Apotex says would not have been done by a Skilled Person.  
6.  
Attempt to form an acceptable salt of ODV  
[52] The third option pursued by Wyeth (after the fumarate salt and pro-drug) to improve  
ODVs absorption/permeability was to attempt to identify a new salt form of ODV. It was known  
that ODV existed as the salt form ODV fumarate as discussed above, but ODV fumarate was not  
pursued as such. It was also known that ODV existed as a free base, but ODV as a free base is  
 
Page: 23  
insoluble in water which I accept leads to absorption issues; therefore the ODV free base was not  
pursued.  
[53] I also accept that it was known, as stated by Dr. Shah, that salt formation provides a  
means of altering the physicochemical properties of a drug - like solubility and stability - without  
modifying its chemical structure. It is also accepted that salts are formed by interacting an acid  
and a base together to form a salt.  
[54] ODV is a base. Therefore, in order to attempt to make a salt with ODV, it was necessary  
to interact the base, ODV, with an acceptable acid.  
[55] ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| As a result, most of the pre-clinical work on ODV conducted by  
the Discovery Group was conducted on ODV fumarate, but as noted already, ODV fumarate  
displayed poor oral bioavailability.  
[56] |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| , Dr. Shah  
proceeded to investigate other salt forms of ODV. This work began by his consulting  
Dr. Hadfield of Wyeths Salt Selection Committee for assistance with preparing and screening  
new salts. ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
Page: 24  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
[57] Dr. Shah and Dr. Hadfield started the salt screening process by preparing the  
|||||||||||||||||||||||||||||||||||||||||||||||| salt of ODV. ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
[58] However, the |||||||||||||||||||||||||||||||| salt of ODV displayed unfavorable properties for further  
drug development. ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
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[59] After discarding the |||||||||||||||||||||||||||||||| salt as a candidate, Wyeth continued to prepare and  
test other salt forms of ODV. Its goal was to identify salt forms of ODV that would exhibit a  
suitably low level of hygroscopicity, and display other properties necessary for development  
(such as crystallinity, aqueous solubility and stability). Dr. Shah stated that all of this was  
necessary before Wyeth could even get to the stage of testing permeability or bioavailability.  
[60] Dr. Hadfields lab notebook confirms that Wyeth attempted to prepare a number of  
different salts of ODV over the summer of 2000, including:  
(a) ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
(b) ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
(c) ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
(d) ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
(e) ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
(f) ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
(g) ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
[61] In addition to these counter-ions, Wyeth tested additional salts in June and July of 2001.  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
(a) ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
(b) ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
Page: 26  
(c)  
Mono-carboxylic counter-ions (like acetate), di-carboxylic counter-ions (like  
succinate, maleate and tartrate), and tri-carboxylic counter-ions (like citrate).  
[62] In addition, Wyeth also screened other types of salts following August 2000, ||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
[63] Apotex notes that ODV succinate was one of the first salts identified after Wyeths salt  
screening commenced; |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| , as reported in para 60(e) above.  
7.  
Polymorph and crystal screening  
[64] Having identified these salts, the next step deposed to by Dr. Shah, who was present  
throughout these experiments as manager of commercialization of ODV, was to determine  
whether any the identified salts of ODV could be made as crystalline solids. Crystalline solids  
were preferable for development because they were often more stable and less hygroscopic than  
non-crystalline (amorphous) solids.  
[65] ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
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[66] ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
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[67] While crystallinity was highly desirable for a drug candidate, Dr. Shahs evidence, which  
I accept, was that not every crystalline salt would have suitable properties for drug development.  
Potential salts therefore also had to be evaluated for solubility, physical and chemical stability,  
and bioavailability. It is not disputed that all of these properties are not necessarily found  
together in any one salt; for example, a salt that displayed good crystallinity and solubility may  
not have good physical stability (and vice versa).  
[68] I therefore accept Dr. Shahs evidence that Wyeth was looking to develop the salt with  
the best combination of properties it could find. Because there was no way of predicting the  
characteristics of a salt at the outset, Dr. Shahs team continued to explore multiple candidates  
and screen further salts as other candidates advanced through solubility, stability and  
bioavailability testing. This allowed them to have alternative salt forms ready in the event that  
the leading salt forms displayed unfavorable properties in further testing.  
Page: 28  
8.  
Solubility  
[69] After identifying these crystalline salts, Wyeth next evaluated the solubility of the  
potential drug candidates. Solubility of a drug candidate was important. In order for an oral dose  
of a drug to be absorbed in the GI tract, it needed to have acceptable solubility to be in solution  
at the three sites of absorption (the stomach, the small intestine and the large intestine), each of  
which have different pH levels. Typically the pH of the stomach is 1.0, the pH of the small  
intestine is around 5.5, and the pH of the large intestine is around 7.0. This meant that the  
solubility of the salt had to be acceptable at each of these three pH levels.  
[70] In addition, Wyeth was looking for a drug candidate that could be administered once a  
day. Therefore, I accept that it did not want solubility to be too high, as this could cause the drug  
to be dissolved all at once and thus absorbed too quickly in the stomach; such rapid absorption  
would not be ideal for a once-a-day formulation as it might also cause nausea and emesis  
(vomiting) which had been exhibited with venlafaxine. Dr. Shah deposed that Wyeth was  
looking for a salt with solubility better than what was observed for ODV fumarate.  
[71] In this connection, ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
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more soluble which made it a likely candidate for further drug development.  
9.  
The Preparation of ODV Succinate  
[72] Given this, it is not surprising and the evidence I accept is that the salt form Wyeth chose  
for further evaluation was the succinate salt of ODV. ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Once it was determined to form as a solid,  
Dr. Hadfield attempted to induce it into a crystalline form, using a variety of solvents. ||||||||||||||||  
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[76] Dr. Shahs evidence which I accept was that ODV succinate monohydrate appeared to  
have properties desirable for a drug candidate.As a result, it was promoted (along with some of  
the other salts of ODV that had been prepared) to permeability and bioavailability testing to see  
if it would fare better than the fumarate salt form.  
Page: 31  
10.  
Permeability and bioavailability testing  
[77] Dr. Shahs evidence, which again I accept, was that the most promising ODV salt forms  
were tested in several bioavailability models, |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| and in vivo (in the  
body). His teams goal in conducting this bioavailability testing was to identify a form of ODV  
that would have sufficient permeability across the entire GI tract to best support once-a-day  
dosing.  
[78] |||||||||| permeability tests, ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
|||||||||||||||||||||||||||||||||||||||||| and the in vivo rat perfusion test, were initial keys in determining which salt,  
if any, might support once-a-day dosing.  
11.  
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[79] ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
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[82] However, regarding point 1, Dr. Shah testified that in another case in which White &  
Case, a US law firm was involved, he was told that they had tried to obtain that information and  
were not able to find the ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
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[83] ||||||||||||||||||||||||||||||||||||||||||, Dr. Shahs reply affidavit clearly rejected Apotexs concerns, which I  
find were speculative to being with. Dr. Shah deposed:  
4.  
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[84] Dr. Shahs explanation makes sense and I accept that ODV fumarate was a natural  
reference salt for permeability testing of novel salt forms, which included ||||||||||||||||||||||||||||||||||||||||||||  
| | | | and the rat perfusion in vivo tests.  
12.  
Rat perfusion test  
[85] A rat perfusion test is an in vivo (inside the body) test that directly measures the  
absorption properties of a compound in three regions of the GI tract of a rat: the duodenum-  
jejunum, the ileum, and the colon. I accept that this test was used by Wyeth because the literature  
established rat perfusion testing was a reliable predictor of a compounds absorption in the  
various regions of the human GI tract.  
[86] Dr. Shahs evidence was that although it was most difficult to achieve permeability  
through the colon wall, absorption in the colon was desired to support once-a-day dosing.  
[87] The rat perfusion tests involved injecting a solution of ODV succinate directly into  
clamped off sections of the GI tract of living male rats (the duodenum, jejunum, ileum and  
 
Page: 34  
colon). The rats were anesthetized and small segments of their GI tracts were surgically isolated  
for this permeability testing. The concentration of ODV succinate was measured at each time  
point using a known analytical technique. The difference in concentration between the inflow  
and the outflow represented the amount of drug absorbed by that segment of the GI tract over  
that period of time.  
[88] ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
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||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
[89] The results of the rat perfusion assay are reported in terms of Peffvalues. Peff value is  
the rate of perfusion (in cm/sec) of the drug across the intestinal wall.  
[90] From the Peff value the evidence is that one may calculate, using a known equation, the  
predicted amount of the drug that would be absorbed through the human GI tract. This  
calculation results in what is known as a Favalue (fraction absorbed), which is the  
percentage of the drug present reliably predicted to be absorbed in the human GI tract.  
Page: 35  
[91] The results of |||||||||||||||||||| rat perfusion test were surprising in terms of the permeability of  
ODV succinate. ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||, ODV succinate was more permeable than ODV fumarate; ODV fumarate was  
significantly less permeable than ODV succinate in all tested GI segments. Moreover, ODV  
fumarate had both Peff and therefore Fa values lower than ODV succinate in all regions.  
[92] Importantly given Dr. Shahs evidence concerning absorption in the colon, while ODV  
fumarate showed no absorption in the colon, ODV succinate was permeable throughout the GI  
tract including the colon. Indeed, it had a Fa value of 16% in the colon (compared with 0% for  
ODV fumarate).  
[93] This result was surprising because, as Dr. Shah had explained earlier, it was not expected  
that any difference in solubility between the two salts would be a factor in the extent of their  
permeabilities. Since both salt forms were completely soluble at the concentration used for each  
experiment, the ODV cation (the ion with a net positive charge in solution) would have been  
anticipated to be dissociated from its fumarate or succinate anion (the ion with a negative charge  
in solution). In both experiments, the ODV cation should have been able to diffuse through the  
wall of the GI segment without any significant impact from the anion (because in solution the  
two counter ions are kept separated by water molecules).  
[94] To Dr. Shahs knowledge, which I accept, ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| His evidence was  
Page: 36  
also that although ODV succinate certainly had higher solubility (which can be one factor that  
contributes to GI perfusion), ODV fumarate would have been expected to behave similarly to  
ODV succinate. He deposed that ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
[95] Apotex raises issues in connection with the rat perfusion tests (going to Apotexs inutility  
argument). Apotex argued that the rat perfusion tests were not demonstrative but only predictive,  
that the tests only showed comparable not improved absorption and were themselves unreliable,  
and that other Wyeth tests showed ODV free base, fumarate and succinate were all favourable  
which test results were not available. I accept Dr. Shahs evidence in interpreting the results over  
that of Dr. Bastin on the first two points, and am not persuaded that Dr. Shah was being anything  
but truthful in his evidence on the third. In connection with missing reports it should be recalled  
that |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| , all of  
which were exhibited to Dr. Shahs affidavit.  
13.  
Beagle dog testing  
[96] Having observed and documented ODV succinates superior solubility together with its  
improved permeability over ODV fumarate in the rat perfusion tests, and the relatively poor  
bioavailability of ODV fumarate previously observed in mice, Wyeth moved on to determine  
whether ODV succinate would have suitable bioavailability in another reliable in vivo system  
used for testing drug development, namely beagle dogs. Dr. Shahs evidence which I accept, was  
that [B]ased on its superior solubility and permeability characteristics, we expected that ODV  
 
Page: 37  
succinate would have improved bioavailability over ODV fumarate and would be appropriate for  
a once a day, extended release formulation. It was therefore selected for further development.”  
[97] Thus ODV succinate was advanced to in vivo beagle dog tests. However, the fumarate  
salt was not subject to beagle dog testing because Wyeth had already established that ODV  
fumarate had poor bioavailability.  
[98] In the beagle dog testing, Dr. Shahs evidence, which I accept, was that Wyeth was  
looking for an oral dosage form of ODV succinate to administer to the dogs to evaluate oral  
bioavailability. As part of the development efforts, Wyeth had started experimenting with  
different formulations of ODV succinate (i.e., different combinations of ingredients mixed with  
ODV succinate to produce solid dosage forms, like tablets). In particular, in accordance with its  
goal of achieving once-a-day dosing, Wyeth was already working on developing an oral  
sustained release formulation of ODV succinate.  
[99] The beagle dog test was conducted using several different ODV succinate formulations,  
including intravenous, oral solution plus two other oral formulations: a capsule designed for  
immediate release, and a tablet designed for sustained release. The tests proceeded in four stages.  
In each stage, the beagles received one of the four different formulations of ODV succinate.  
Blood was taken from the dogs at specified intervals during each stage and was separated, frozen  
and shipped once again to Wyeths Gosport facility in the United Kingdom for analysis. The  
Page: 38  
concentrations of ODV present in the blood were determined by accepted methods and a number  
of pharmacokinetic parameters were calculated.  
[100] The results of the beagle dog bioavailability testing are summarized in ||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| a table summarizing the mean data from all six dogs  
as a function of the concentration of free ODV in the blood. The pharmacokinetic parameters  
reported in the table include:  
(a) AUC (area under the curve) - which measures the total amount of ODV present in  
the blood over the time course of the experiment;  
(b) Cmax - which measures the peak plasma concentration of ODV;  
(c) tmax - which measures the time at which peak concentration occurs; and  
(d) absolute bioavailability-which measures the amount of ODV (as a percentage of the  
dose administered) found in the plasma.  
[101] ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
Page: 39  
[102] The conclusion of this beagle dog testing, which I accept, is that the oral bioavailability  
of ODV succinate in beagle dogs fell within an acceptable range in all formulations tested.  
14.  
Human testing  
[103] With the |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| in vivo testing in rats and beagle dogs showing  
positive results, Wyeth moved to testing in with 18 human volunteers.  
[104] Wyeths human in vivo oral bioavailability studies of ODV succinate were conducted by  
comparing immediate release and sustained release formulations of the ODV succinate salt,  
against Wyeths already successfully commercialized sustained release venlafaxine product  
EFFEXOR XR.  
[105] As in Wyeths in vivo beagle dog studies, its human study ran in three stages. In each  
stage each of the 18 human participants were given 75 mg of EFFEXOR XR as the comparator  
to the immediate and sustained release formulations of ODV. Blood samples were taken at  
specific time periods in each stage and the concentrations of venlafaxine and ODV in the blood  
were measured. A number of the same pharmacokinetic parameters were calculated (AUC,  
Cmax, tmax) as well as t 1/2 (which measures the amount of time it takes for half of the drug to  
be eliminated from the plasma). ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||  
 
Page: 40  
[106] The results of the human studies are summarized in ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
Again, Wyeth noted that oral bioavailability was good in both the immediate and sustained  
release formulations of ODV succinate. However, the sustained release formulation of ODV  
succinate resulted in peak plasma concentrations that were lower, and the time to maximal  
concentration was longer, than observed with the immediate release formulation.  
[107] The human study was also designed to observe side effects of ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
|||||||| and ODV succinate. Dr. Shah deposed that while conducting the human studies, Wyeth  
noted the reports of adverse events or side effects experienced with the various formulations.  
Wyeth was interested in monitoring several common adverse events (such as nausea, vomiting,  
etc.) because they were frequently reported with the use of EFFEXOR. Wyeth noticed that the  
reported adverse events were lower with the sustained release formulation of ODV succinate  
than with the immediate release formulation - a fact I accept. Wyeth surmised that this was likely  
due to the lowered peak plasma concentration (Cmax) and delayed time to peak plasma  
concentration (tmax) achieved with the sustained release formulation.  
[108] Based on its data, Wyeth concluded that sustained release formulation of ODV succinate  
which resulted in peak plasma concentrations of less than 225 ng/mL (the lower end of the range  
observed for the immediate release formulation) would result in a reduction of these side effects.  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
Page: 41  
[109] Dr. Shah deposed, and I accept that from this human in vivo testing, as a flattened blood  
plasma concentration to time profile was achieved, adverse events were reduced or eliminated.  
Thus, a pharmaceutical composition comprising a sustained release formulation of ODV  
succinate having a peak blood plasma profile of less than about 225 ng/ml with reduced side  
effects such as nausea and emesis (vomiting) had been achieved.  
[110] The evidence is and I find that the lower end of the range observed for the immediate  
release formulation, as deposed to by Dr. Shah, namely 225 ng/ml, is the derived result of the  
human subject testing which showed that the Cmax of the immediate release form of ODV  
succinate was 287 plus or minus 52, such that the lower end of the range was 225 ng/ml; this is  
the result disclosed on page 53 of the 668 Patent. Thus I reject Apotexs argument that this  
concentration is arbitrary.  
[111] I also find that the sustained release version of ODV succinate showed considerably  
lower adverse side effects when compared to the immediate release version of ODV succinate.  
Of the 18 subjects given the immediate release single dose of ODV succinate, 10 and 6 reported  
nausea, 2 vomiting, 1 diarrhea, 1 abdominal pain, 2 headache, 2 vaso-vagal malaise and 1  
reported trismus. There were only 2 reports of nausea with the sustained release version of ODV  
succinate, and 1 of abdominal pain; none of the human test subjects reported any other adverse  
side effect noted with the immediate release dosage. Dr. Shah properly noted in his affidavit that  
the report at page 54 of the 668 Patent, through a typographical error, reported no reports of  
abdominal pain with either the immediate or sustained versions of ODV succinate when in fact  
Page: 42  
there was one report for each: this error is not material to the improvement in side effects of the  
sustained release version over the immediate version; as Dr. Shah deposed it does not affect the  
overall conclusion that the incidence of adverse events was lower for ODV succinate sustained  
release than ODV succinate immediate release.  
15.  
Solid state forms: crystallinity, amorphous solids, polymorphs  
[112] Dr. Shahs evidence, which again I accept, was that a criterion for a viable drug form was  
a drug form that could exist as a crystal, or exhibit crystallinity. Crystallinity refers to the  
organization of the molecules in a drug compound (or salt) in three-dimensional space. In a  
crystalline solid, the molecules making up the substance are organized in repeating patterns. By  
contrast, non-crystalline solids (often referred to as amorphoussolids) have molecules that are  
randomly arranged. Crystalline solids were preferable for pharmaceutical drug form  
development because they were typically more stable than amorphous solids.  
[113] Further, Dr. Shah deposed, and I accept that some compounds may exist in more than one  
solid-state form, which may include amorphous forms and/or one or more crystalline forms.  
Different crystalline forms of the same compound are usually referred to as polymorphs.  
Dr. Shahs group understood that different polymorphs of the same compound could have very  
different physical properties (such as solubility, melting point and stability), and that these  
properties could be relevant to drug form development.  
16.  
Polymorph screening and subcontracting polymorph screening to SSCI, Inc.  
   
Page: 43  
[114] As outlined above, when conducting preliminary screening of ODV succinate for  
crystallinity, Dr. Shah and Wyeths Dr. Hadfield created a stable and soluble crystalline  
monohydrate form. However, in order to ultimately develop the compound as a drug, Dr. Shahs  
evidence, which I accept, was that it was important to have a stable and reproducible solid form  
that would not be susceptible to degradation or conversion during storage under different  
humidity conditions at room temperature and during the manufacturing and distribution  
processes. Therefore, to have a better idea of the range of possible solid state forms for a given  
salt, and to determine their individual properties, as well as for possible regulatory compliance,  
Wyeth considered it necessary to undertake a complete polymorph screen for ODV succinate.  
[115] I accept Dr. Shahs evidence that a polymorph screen is a process of discovering further  
unknown crystal forms of a substance by exposing the substance to a number of different  
solvents and conditions, and subsequently characterizing the resulting forms (whether crystalline  
or amorphous). Through this process the drug commercialization developers could get an idea of  
what the various crystal forms of a compound might be, and under what conditions they may be  
expected to form. Dr. Shah added that this process is labour intensive and often involves many  
individual experiments, and that ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||  
[116] ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
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|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Because finding a stable solid  
form that could be consistently prepared was very important to further development, for this  
reason also Wyeth determined that a detailed investigation of the solid forms of ODV succinate  
was necessary to define possible crystal forms.  
[117] As a result, Wyeth retained an outside scientific consulting group, SSCI to conduct a  
detailed polymorph screen of ODV succinate. Wyeth asked SSCI to:  
(a) ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
(b) ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
(c)  
Determine the relative thermodynamic stabilities of the formcs under various  
conditions.  
[118] As a result of its work, SSCI identified and characterized four crystal forms of ODV  
succinate as well as one amorphous form; three of the crystal forms SSCI identified for the first  
time, the fourth was the crystal form developed by Wyeth which Wyeth gave to SSCI for its  
work.  
[119] |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Dr. Shah concluded |||||||||||||||||||||||||||||||||||||||||||||||| that  
one particular crystal form of ODV succinate monohydrate ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||, but  
which is now known and described in the 668 Patent as Form I ODV succinate) ||||||||||||||||||||||||||||||||||  
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| could be expected to be stable under the  
conditions required for manufacturing and storage. This, combined with the other favorable  
Page: 45  
properties of ODV succinate, made Form I ODV succinate a very attractive candidate for  
development as a drug.  
17.  
Dr. Aeri Park at SSCI  
[120] The person managing the team of scientists conducting SSCIs work on ODV succinate  
was Dr. Aeri Park. Dr. Park studied and worked in the field of chemistry for 30 years, and has  
worked specifically in the area of drug development and characterization for 20 years. She began  
working as a Technician for SSCI in 1998 and was promoted to the role of Scientist that same  
year. She was promoted to Senior Scientist in 1999, to Senior Research Investigator in 2000, and  
to Director in 2001. As a Director, she was responsible for managing multiple teams of scientists  
working on solid state chemistry projects, interacting with clients and identifying new  
approaches and potential routes of analysis for our projects. She was also responsible for  
providing training to new scientists on how to use the wide range of instrumentation and  
laboratory tools at SSCIs laboratory. Her involvement with the ODV succinate project began in  
2001, when Wyeth retained SSCI to conduct a complete polymorph screen of ODV succinate.  
[121] I accept Dr. Parks evidence of what SSCI did because of her experience and personal  
involvement with this particular compound and relevant knowledge of work in this area. She  
oversaw the work conducted by specialized SSCI scientists primarily responsible for carrying out  
the day-to-day experimentation on the ODV succinate project; these scientists reported directly  
to her. Dr. Park is one of the named inventors on the 668 Patent, but I am not persuaded this  
affected her evidence in any way.  
 
Page: 46  
[122] ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
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[123] ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
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|||||||||||||||||||||||||||||||||||||||||||||||| Dr. Park deposed, and I accept, that SSCIs goal was to try as many  
different conditions as possible, because different conditions could produce different polymorphs  
and pseudo-polymorphs. Conditions like the solvents used, temperature, rate of cooling, time  
course, the experiment and the presence of other reagents are all examples of matters that may  
affect the solid state form of the compound. Therefore, Dr. Park deposed and based on her  
personal experience I accept, that SSCI typically conducted a large number of different  
experiments under a wide variety of conditions in order to try to identify as many different solid  
state forms as possible.  
Page: 47  
[124] Dr. Parks experience-based evidence was that the creation and analysis of new solid  
state forms in not a rote process. Having carried out or supervised some 10 to 20 polymorph  
screens per year during her tenure at SSCI, I accept her expert evidence on crystal and  
polymorph screens generally; by the times in issue she would have carried out or supervised 10  
to 20 or more polymorph screens. Her evidence was as follows:  
Polymorph Screens  
20.  
I carried out or supervised approximately 10-20 polymorph  
screens per year during my tenure at SSCI. Screens typically took  
three to four months to complete but he timing depended on the  
project, the sample and the goals of the client.  
21.  
Screens broadly followed the frame-work of answering the  
questions identified in the ICH Q6A, a guideline developed by the  
International Council for Harmonisation of Technical  
Requirements for Registration of Pharmaceuticals for Human Use.  
While each polymorph screen generally followed this same broad  
framework such as starting by identifying the solid state forms of  
the provided sample and then carrying out a range of experiments  
to attempt to generate additional solid samples each screening  
project was different. For example, in one screen we might  
discover only one crystalline form, whereas in another we might  
find many. In yet another scenario, we might not be able to  
generate crystalline material at all. The duration, direction, results  
and steps to be taken in each project depended on the  
characteristics of the compound being studied and the goals of our  
client.  
22.  
At regular intervals throughout the screening project, I  
would discuss the experimental results to date with the members of  
my team, and we would decide on what additional experiments and  
analyses to conduct, in light of the results obtained thus far. The  
end goal was usually, but not always, to identify the most stable  
solid state crystal form of the sample provided, but this was not  
always possible.  
[Emphasis added.]  
Page: 48  
[125] Dr. Park further deposed:  
Generating Solid Samples  
34. Our goal in generating solid samples was to try as many  
different conditions as possible because different conditions could  
produce different polymorphs and pseudo-polymorphs of the  
compound. Conditions like the solvent(s) used, the temperature,  
the rate of cooling, the time course of the experiment and the  
presence of other reagents are all examples of things that can affect  
the solid state form of the compound, if any, that is produced.  
Therefore, we would typically conduct a large number of different  
experiments under a wide variety of conditions in order to try to  
identify as many different solid state forms as possible.  
35.  
There were several different methods that we could use to  
try to generate different solid state forms from solution. These  
were, generally speaking, divided into methods involving  
thermodynamic conditions and methods involving kinetic  
conditions. ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
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36.  
The creation and analysis of new solid forms was not a rote  
process. It was not possible for us to predict at the outset how  
many solid forms we would be able to identify, what they would  
be, or what solid forms would result from any particular method or  
set of conditions. Therefore, this process often required numerous  
experiments and analyses, and strategy and judgment had to be  
employed in order to make decisions about how to proceed based  
on the results that we obtained.  
[Emphasis added.]  
Page: 49  
[126] In the process of creating and identifying new solid state forms, Dr. Park and SSCI  
conducted numerous other studies and experiments, as outlined below:  
Characterization of Initial Solid Samples  
42.  
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||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||  
49.  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||  
50.  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
Page: 51  
51.  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
Other Techniques for Analysis and Characterization  
52.  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
53.  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||  
[Emphasis added.]  
[127] ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||  
18.  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
[128] ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
 
Page: 52  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
19.  
Melting points and differential scanning calorimetry (DSC)  
[129] ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||, SSCI also conducted DSC analyses on the crystal forms  
in order to determine the temperatures at which phase transitions (like melting) occurred. DSC is  
a technique of measuring a melting event. Based on these analyses, the melting point of  
Form Awas determined to be about 131°C (endothermic maximum) and the melting point of  
Form Bwas determined to be about 127°C (endothermic maximum). The DSC data did not  
show any dehydration event but showed a single melting event which showed that water  
molecules were very strongly bound in the crystalline lattices of Form Aand Form B. This  
was consistent with the TGA data, where the loss of water did not occur past 100°C. Hydrates  
 
Page: 53  
tend to lose the water of crystallization fairly readily at elevated temperatures due to dehydration,  
and convert to anhydrous crystalline forms or non-crystalline material.  
[130] Therefore, the DSC |||||||||||||||||||| data indicated that Forms Aand Bare very stable  
hydrates. ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||  
20.  
Further temperature studies and amorphous form  
[131] ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| One of the additional  
tests that they performed during this time was variable temperature XRPD (VT-XRPD), which  
involved running XRPD analyses over a range of temperatures to check for changes in the  
resulting diffractograms. Using this test they could observe whether or not the crystal form was  
stable to changes in temperature or whether it would change or convert to another form. ||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||  
[132] During these studies they also identified an amorphous (non-crystalline) form of ODV  
succinate ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
 
Page: 54  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
21.  
Hygroscopicity testing (a test relevant to drug stability)  
[133] ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||  
22.  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
[134] ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
   
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23.  
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[136] SSCI thereby identified crystal forms A, Band C, and then identified crystal form  
Dthrough ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
24.  
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[138] ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
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[139] SSCI ultimately identified four polymorph forms of ODV succinate, namely Forms A,  
B, Cand D. Of these Form A had already been discovered by Wyeth; Wyeth had provided  
Form Ato SSCI. Therefore, SSCI succeeded in identifying three new crystalline forms of  
ODV succinate. SSCI also identified one new amorphous form. In all, five forms of ODV  
succinate were identified by SSCI, four for the first time.  
[140] ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
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[141] In essence, while Wyeths Dr. Hadfield had identified ODV succinate as a salt and as a  
crystal, the specialists at SSCI after thoroughly exploring the field, determined there were three  
other crystalline forms of ODV succinate plus one amorphous form. ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
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25.  
Work on other salt candidates and screens  
[142] Notwithstanding Wyeth and SSCI had made a new composition of matter namely Form I  
ODV succinate in a crystalline form, Dr. Shahs evidence, which I accept, was that ||||||||||||||||||||||||  
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[143] ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
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||||||||||||||||||||||||||  
26.  
Miscellaneous  
[144] While Apotex raised issues in connection with the invention story concerning the  
racemate and enantiomers of ODV succinate in its NOA and based on evidence supplied by  
Apotexs Drs. Bastin and Steed, it did not pursue this issue in its memorandum or at the hearing.  
VI.  
Issues  
[145] The issues remaining in this application are:  
1. Whether Pfizer has discharged its burden to establish on a balance of probabilities  
that Apotexs allegation of obviousness is not justified.  
2. Whether Pfizer has discharged its burden to establish on a balance of probabilities  
that Apotexs allegation of inutility is not justified.  
3. Whether Pfizer has discharged its burden to establish on a balance of probabilities  
that Apotexs allegation of non-infringement is not justified.  
4. Whether Pfizer has discharged its burden to establish on a balance of probabilities  
that Apotex’s allegation of overpromising in relation to subsection 27(3) of the  
Patent Act is not justified.  
5. Whether Pfizer has discharged its burden to establish on a balance of probabilities  
that Apotexs allegation of anticipation is not justified.  
   
Page: 60  
6. Whether Pfizer has discharged its burden to establish on a balance of probabilities  
that Apotexs allegation of double patenting is not justified.  
VII. Statutory provisions and burden of proof  
[146] Pursuant to section 2 of the Patent Act, in order to be patented, an invention must be  
newand useful. Further, a new and useful composition of mattersuch as Pfizer claims  
here, may be patented:  
invention means any new and invention Toute réalisation,  
useful art, process, machine,  
tout procédé, toute machine,  
manufacture or composition of fabrication ou composition de  
matter, or any new and useful  
improvement in any art,  
matières, ainsi que tout  
perfectionnement de lun  
process, machine, manufacture deux, présentant le caractère  
or composition of matter;  
(invention)  
de la nouveauté et de lutilité.  
(invention)  
[Emphasis added.]  
[Soulignements ajoutés.]  
[147] In Novartis Pharmaceuticals Canada Inc v Cobalt Pharmaceuticals Company, 2013 FC  
985 [Novartis], Justice Hughes said the following regarding the burden of proof applicable in  
cases where a patents validity is challenged in an NOC proceeding:  
[23] Who bears the burden when validity of a patent is at issue  
in NOC proceedings has been discussed many times in this Court.  
In brief: a patent is presumed to be valid in the absence of evidence  
to the contrary (Patent Act, s. 43(2)). The party alleging invalidity  
(here Cobalt) has the burden of putting forth evidence supporting  
its allegations. Once evidence is led the matter is determined by the  
Court on the civil burden of proof; namely, balance of  
probabilities. If the Court finds the matter to be evenly balanced,  
then it should find in favour of the person alleging invalidity since,  
under the NOC Regulations, subsection 6(2), the first person (here  
Novartis) bears the burden of demonstrating that the allegations of  
invalidity are not justified.  
 
Page: 61  
VIII. Analysis  
1.  
Relevant Dates  
[148] The relevant dates are agreed upon and are as follows.  
[149] The 668 Patent was filed in Canada on February 11, 2002, claiming priority to two  
previous applications dated February 12, 2001 and June 13, 2001. The application was published  
on August 22, 2002 and the patent issued on May 26, 2009.  
[150] The relevant dates for assessing obviousness for each of the asserted claims are set out in  
s 28.3 of the Patent Act. For publicly disclosed information originating from the patentee, the  
relevant date is February 11, 2001. For all other publicly disclosed information, the relevant date  
is the claim date.  
[151] Pfizer asserts that it is entitled to rely on its priority applications and that the claim date is  
the first priority date of the 668 patent (February 12, 2001). Apotex disputes that Pfizer has  
established that any one of the claims at issue is entitled to a claim of priority and asserts that the  
claim date is therefore February 11, 2002. However, given that the prior art and common general  
knowledge alleged by Apotex to obviate the asserted claims pre-date both of these dates, it is not  
necessary to resolve this conflict.  
   
Page: 62  
[152] The relevant dates for assessing anticipation are as set out in s 28.2 of the Patent Act. For  
publicly disclosed information originating from the patentee, the relevant date is February 11,  
2001. For all other publicly disclosed information, the relevant date is the claim date. As  
previously discussed, Apotexs position is that the claim date is February 11, 2002, and Pfizers  
position is that the claim date is February 12, 2001. However, given that the references alleged  
by Apotex to be anticipatory pre-date both of these dates, the parties agree that it is not necessary  
to resolve this conflict.  
[153] The parties agree that utility (whether demonstrated or soundly predicted) should be  
assessed as of the Canadian filing date, in this case February 11, 2002.  
[154] It is not disputed that the 668 Patent is to be construed from the perspective of a person of  
ordinary skill in the art as of the date of publication: August 22, 2002.  
2.  
Claims Construction  
[155] Claim construction is a question of law to be determined by the Court. Where the  
meaning of terms or elements of claims are not apparent from a reading of the claim itself or  
from reference to the specification, the experts may provide guidance on this matter. The claims  
are to be construed, as they would be read by a Skilled Person, at the relevant date, looking to the  
patent with a view to understand: Gilead Sciences, Inc v Canada (Health), 2016 FC 856 at  
paras 37-38.  
 
Page: 63  
[156] In this connection, Justice Kane in Alcon Canada Inc v Apotex Inc, 2014 FC 699 cited  
Justice Hughes with approval on the principles of claim construction:  
[121] Justice Hughes provided a useful summary of the relevant  
principles following a review of all the jurisprudence in Pfizer  
Canada Inc v Pharmascience Inc, 2013 FC 120, [2013] FCJ No  
111:  
[64] There have been many judicial instructions  
as to the construction of a claim. To summarize:  
• construction must be done before considering the  
issues of validity and infringement;  
• construction is done by the Court alone, as a  
matter of law;  
• the Court is to construe the claim through the eyes  
of the person skilled in the art to which the patent  
pertains;  
• the Court may obtain the assistance of experts to  
explain the meaning of particular words and  
phrases, and as to the state of the art as of the date  
the claim was published;  
• the Court should read the claim in the context of  
the patent as a whole, including the description and  
other claims;  
• the Court should avoid importing this or that gloss  
from the description;  
• the Court should not restrict the claim to specific  
examples in the patent;  
• the Court should endeavour to interpret the claim  
in a way that gives effect to the intention of the  
inventor;  
• the Court should endeavour to support a  
meritorious invention.  
Page: 64  
[157] Pfizer also notes that a patent should be read purposivelyfrom the perspective of a  
person of ordinary skill in the art to which the patent relates. Purposive construction requires the  
Court to consider the words of the claims in light of the whole specification. While the words of  
the patent govern, the Court must consider the context in which they appear. The construction  
should be one that is in the interest of fairness both to the patentee and the public: Whirlpool  
Corp v Camco Inc, 2000 SCC 67 at paras 45, 49, 52-53.  
[158] The parties dispute the construction of the asserted claims, mainly in respect of Claims 8  
and 9. The following is a claims chart prepared by the parties setting out each claim in issue, the  
claims from which they depend (for context), and the partiespositions on construction. Note  
that while more are outlined below, only Claims 8, 9, 33, 43 and 44 are asserted by Pfizer:  
Claim  
No.  
Depends  
From  
Claim Language  
Pfizers Position Apotexs Position  
on Construction on Construction  
1.  
None  
A compound which  
is O-desmethyl-  
venlafaxine  
succinate or a mixed  
salt thereof.  
Not asserted.  
Encompasses all  
crystalline and  
Covers ODV  
succinate, or  
alternatively, a  
mixed ODV  
succinate salt, in  
any form.  
amorphous forms,  
mono and bi ODV  
succinate salts, as  
well as mixed salts  
of ODV succinate.  
2.  
3.  
Claim 1.  
Claim 1.  
A compound  
Encompasses Form  
I (unground), Form  
I (ground), Forms  
II, III and IV, and  
the amorphous  
form.  
Not asserted.  
according to claim 1  
wherein the ratio of  
O-desmethyl-  
venlafaxine to  
succinic acid is 1:1.  
Covers ODV  
mono succinate in  
any form.  
A compound  
Covers bi ODV  
succinate in any  
form.  
Not asserted.  
according to claim 1  
wherein the ratio of  
O-desmethyl-  
Covers ODV bis  
succinate in any  
Excludes Form I  
Page: 65  
Claim  
No.  
Depends  
From  
Claim Language  
Pfizers Position Apotexs Position  
on Construction on Construction  
venlafaxine to  
succinic acid is 2:1.  
form.  
(unground), Form I  
(ground), and Form  
II, III and IV.  
4.  
Claim 1.  
A compound  
Encompasses Form  
I (unground), Form  
I (ground) and  
Not asserted.  
according to claim 1  
which is a hydrate of  
O-desmethyl-  
venlafaxine  
Covers any  
hydrated form  
(i.e., a form in  
which water is  
present in the  
crystal lattice) of  
ODV succinate.  
Forms II and III.  
Form IV, and the  
amorphous form are  
excluded.  
succinate.  
5.  
Claim 1.  
A compound  
according to claim 1  
which is O-  
desmethyl-  
venlafaxine  
Encompasses Form  
I (unground), Form  
I (ground) and Form  
II.  
Not asserted.  
Covers any  
monohydrated  
form of ODV  
succinate (i.e.,  
wherein there is  
one molecule of  
water present in  
the crystal lattice  
for every  
Forms III and IV,  
and the amorphous  
form are excluded.  
succinate  
monohydrate.  
molecule of ODV  
succinate).  
6.  
Claims 1, 2, 4  
or 5.  
A compound  
As it depends on  
claim 5, the claim  
encompasses Form I  
(unground), Form I  
(ground) and Form  
II.  
Not asserted.  
according to any one  
of claims 1, 2, 4 and  
5 wherein the salt is  
crystalline.  
Covers any  
crystalline form  
of ODV succinate  
(or a mixed salt  
thereof). As it  
depends on claim Forms III and IV,  
5, covers any  
and the amorphous  
form are excluded.  
crystalline form  
of ODV succinate  
monohydrate.  
8.  
Claim 6, which A compound  
in turn depends according to claim 6 ODV (mono)  
from claims 1, which exhibits an X- succinate  
Covers Form I  
Covers ODV  
succinate that  
satisfies the  
Page: 66  
Claim  
No.  
Depends  
From  
Claim Language  
Pfizers Position Apotexs Position  
on Construction on Construction  
2, 4 or 5.  
ray powder  
monohydrate (i.e., requirements of  
diffraction pattern  
the crystalline  
claim 6, which  
having characteristic form of ODV  
depends on any one  
of claims 1, 2, 4 or  
5, and that exhibits  
the specific XRPD  
peaks set out in  
claim 8.  
peaks expressed in  
degrees 2θ (+ 0.2°  
2θ) at 10.20, 14.91,  
succinate, which  
exhibits the  
characteristic  
20.56, 22.13, 23, 71, XRPD peaks of  
24.60, and 25.79.  
Figure 1).  
Claim 8 is not a  
claim to Form I per  
se.  
The claim  
encompasses Form I  
(ground).  
Form I (unground),  
II, III and IV and  
the amorphous  
forms are excluded.  
9.  
Claim 6, which A compound  
in turn depends according to claim 6 ODV (mono)  
from claims 1, having an endotherm succinate  
Covers Form I  
Covers any ODV  
succinate that  
satisfies the  
2, 4 or 5.  
at about 131° C.  
monohydrate (i.e., requirements of  
the crystalline  
form of ODV  
succinate, which  
exhibits a  
characteristic  
endotherm at  
about 131°C (¬+  
2°C)).  
claim 6, which  
depends on any one  
of claims 1, 2, 4 or  
5, and that exhibits  
an endotherm of  
131ºC (±1ºC).  
Claim 9 is not a  
claim to Form I per  
se.  
The XRPD pattern  
of claim 8 is not a  
requirement of  
claim 9 because  
claim 9 does not  
depend on claim 8.  
Page: 67  
Claim  
No.  
Depends  
From  
Claim Language  
Pfizers Position Apotexs Position  
on Construction on Construction  
With a variance of +  
1°C (Apotexs  
position), claim 9  
(6, 5, 4, 3, 1)  
encompasses Form I  
(ground).  
Form I (unground),  
and Forms II and IV  
are excluded from  
the claim.  
With a variance of +  
2°C (Pfizers  
position), claim 9  
(6, 5, 4, 2, 1)  
encompasses Form I  
(ground), and Form  
II.  
Form I (unground)  
and Form IV are  
excluded from the  
claim.  
33.  
Any one of  
claim 1 to 20.  
Use of an effective  
amount of O-  
desmethyl-  
venlafaxine  
succinate or a mixed treatment of  
As it depends on  
claims 8 or 9, use claims 8 or 9,  
of Form I ODV  
succinate for the  
As it depends on  
covers an effective  
amount of the  
compounds of  
claims 8 or 9 for the  
treatment of  
salt thereof as  
depression.  
claimed in any one  
of claims 1 to 20 for  
the treatment of  
depression.  
depression.  
See above  
construction of  
claims 8 and 9.  
Encompasses  
intravenous  
administration  
because the claim is  
not specific any  
Page: 68  
Claim  
No.  
Depends  
From  
Claim Language  
Pfizers Position Apotexs Position  
on Construction on Construction  
particular mode of  
administration.  
34.  
35.  
36.  
37.  
Any one of  
claims 1 to 20. amount of O-  
desmethyl-  
Use of an effective  
Construction is the  
same as in claim 33,  
with the exception  
that the use is  
directed to the  
treatment of  
Not asserted.  
As it depends on  
claims 8 or 9, use  
of Form I ODV  
succinate for the  
treatment of  
venlafaxine  
succinate or a mixed  
salt thereof as  
claimed in any one  
of claims 1 to 20 for  
the treatment of  
anxiety.  
anxiety.  
anxiety.  
Any one of  
claims 1 to 20. amount of O-  
desmethyl-  
Use of an effective  
Construction is the  
same as in claim 33,  
with the exception  
that the use is  
directed to the  
treatment of panic  
disorder.  
Not asserted.  
As it depends on  
claims 8 or 9, use  
of Form I ODV  
succinate for the  
treatment of panic  
disorder.  
venlafaxine  
succinate or a mixed  
salt thereof as  
claimed in any one  
of claims 1 to 20 for  
the treatment of  
panic disorder.  
Any one of  
claims 1 to 20. amount of O-  
desmethyl-  
Use of an effective  
Construction is the  
same as in claim 33,  
with the exception  
that the use is  
directed to the  
treatment of anxiety  
disorder.  
Not asserted.  
As it depends on  
claims 8 or 9, use  
of Form I ODV  
succinate for the  
treatment of  
venlafaxine  
succinate or a mixed  
salt thereof as  
claimed in any one  
of claims 1 to 20 for  
the treatment of  
anxiety disorder.  
anxiety disorder.  
Any one of  
claims 1 to 20. amount of O-  
desmethyl-  
Use of an effective  
Construction is the  
same as in claim 33,  
with the exception  
that the use is  
directed to the  
treatment of post-  
traumatic stress  
Not asserted.  
As it depends on  
claims 8 or 9, use  
of Form I ODV  
succinate for the  
treatment of post-  
venlafaxine  
succinate or a mixed  
salt thereof as  
claimed in any one  
Page: 69  
Claim  
No.  
Depends  
From  
Claim Language  
Pfizers Position Apotexs Position  
on Construction on Construction  
of claims 1 to 20 for traumatic stress  
disorder.  
the treatment of  
post-traumatic stress  
disorder.  
disorder.  
38.  
Any one of  
claims 1 to 20. amount of O-  
desmethyl-  
Use of an effective  
Construction is the  
same as in claim 33,  
with the exception  
that the use is  
directed to the  
treatment of  
premenstrual  
dysmorphic  
disorder.  
Not asserted.  
As it depends on  
claims 8 or 9, use  
of Form I ODV  
succinate for the  
treatment of  
premenstrual  
dysphoric  
disorder.  
venlafaxine  
succinate or a mixed  
salt thereof as  
claimed in any one  
of claims 1 to 20 for  
the treatment of  
premenstrual  
dysphoric disorder.  
39.  
Any one of  
claims 1 to 20. amount of O-  
desmethyl-  
Use of an effective  
Construction is the  
same as in claim 33,  
with the exception  
that the use is  
directed to the  
treatment of one of  
the listed disorders.  
Not asserted.  
As it depends on  
claims 8 or 9, use  
of Form I ODV  
succinate for the  
treatment of any  
one of the listed  
conditions.  
venlafaxine  
succinate or a mixed  
salt thereof as  
claimed in any one  
of claims 1 to 20 for  
the treatment of a  
condition selected  
from fibromyalgia,  
agoraphobia,  
attention deficit  
disorder, obsessive  
compulsory disorder,  
social anxiety  
disorder, autism,  
schizophrenia,  
obesity, anorexia  
nervosa, bulimia  
nervosa, Gilles de la  
Tourette Syndrome,  
vasomotor flushing,  
cocaine and alcohol  
addiction, sexual  
dysfunction,  
Page: 70  
Claim  
No.  
Depends  
From  
Claim Language  
Pfizers Position Apotexs Position  
on Construction on Construction  
borderline  
personality disorder,  
chronic fatigue  
syndrome, urinary  
incontinence, pain,  
Shy Drager  
syndrome,  
Raynauds  
syndrome,  
Parkinsons disease,  
and epilepsy.  
40.  
Any one of  
claims 1 to 20. amount of O-  
desmethyl-  
Use of an effective  
Construction is the  
same as in claim 33,  
with the exception  
that the use is  
directed to  
enhancing of  
cognition or for  
cognition  
Not asserted.  
As it depends on  
claims 8 or 9, use  
of Form I ODV  
succinate for  
enhancing  
cognition or for  
cognition  
impairment.  
venlafaxine  
succinate or a mixed  
salt thereof as  
claimed in any one  
of claims 1 to 20 for  
enhancing of  
cognition or for  
cognition  
impairment.  
impairment.  
41.  
Any one of  
claims 1 to 20. amount of O-  
desmethyl-  
Use of an effective  
Construction is the  
same as in claim 33,  
with the exception  
that the use is  
directed to the  
treatment of  
Not asserted.  
As it depends on  
claims 8 or 9, use  
of Form I ODV  
succinate for the  
treatment of  
hypothalamic  
amenorrhea in a  
depress or non-  
depressed human  
female.  
venlafaxine  
succinate or a mixed  
salt thereof as  
claimed in any one  
of claims 1 to 20 for  
the treatment of  
hypothalamic  
amenorrhea in a  
depressed or non-  
depressed human  
female.  
hypothalamic  
amenorrhea in a  
depressed or non-  
depressed human  
female.  
43.  
Any one of  
Use of a  
As it depends on  
As it depends on  
claims 1 to 20. therapeutically  
claims 8 or 9, use claims 8 or 9,  
covers the use of an  
effective amount of a of a sustained  
Page: 71  
Claim  
No.  
Depends  
From  
Claim Language  
Pfizers Position Apotexs Position  
on Construction on Construction  
sustained release  
oral dosage form  
comprising O-  
desmethyl-  
venlafaxine  
succinate or a mixed average blood  
release oral  
dosage form  
comprising Form described in claims  
I ODV succinate  
to induce an  
effective amount of  
ODV succinate as  
8 or 9 in a sustained  
release dosage form  
to induce a blood  
salt thereof as  
claimed in any one  
of claims 1 to 20  
plasma level of no plasma level of no  
more than 225 more than 225  
ng/ml to lower the ng/ml to lower the  
prepared in a dosage overall incidence incidence of  
to induce a blood  
plasma level of no  
more than 225 ng/ml compared to oral  
to lower the  
incidence of nausea, ODV succinate  
vomiting, diarrhea,  
abdominal pain,  
headache, vaso-  
vagal malaise, or  
trismus resulting  
from the oral  
of the specified  
side effects as  
specific side effects  
resulting from the  
oral administration  
administration of of ODV succinate.  
The term  
not so formulated.  
therapeutically  
effective amount”  
conveys that the use  
is for the treatment  
of any disorder  
described and  
claimed by the  
patent (see claims  
33-42). The claim is  
not specific to the  
treatment of  
administration of O-  
desmethyl-  
venlafaxine  
succinate.  
depression.  
Encompasses the  
use of any plasma  
level greater than 0  
ng/ml to below 225  
ng/ml.  
44.  
None.  
A sustained release  
formulation  
comprising O-  
desmethyl-  
venlafaxine  
succinate and a  
pharmaceutically  
A sustained  
release  
formulation  
comprising O-  
desmethyl-  
venlafaxine  
Covers any  
sustained released  
formulation  
containing ODV  
succinate in any  
form (including,  
succinate (in any mono and bi ODV  
succinate salts, the  
acceptable carrier or form, including  
Page: 72  
Claim  
No.  
Depends  
From  
Claim Language  
Pfizers Position Apotexs Position  
on Construction on Construction  
excipient, wherein  
the sustained release succinate) which  
Form I ODV  
amorphous form,  
Form I (ground),  
formulation provides provides average Form (unground),  
peak serum levels of peak serum levels and Forms II, III  
up to 225 ng/ml.  
of up to 225  
ng/ml.  
and IV), providing  
peak serum levels  
of up to 225 ng/ml.  
Encompasses  
sustained release  
formulations that  
provide any plasma  
level greater than 0  
ng/ml to below 225  
ng/ml.  
The claim  
encompasses all  
types of sustained  
release formulations  
(transdermal, oral,  
etc.) because the  
claim is not specific  
to any particular  
type of sustained  
release formulation.  
The claim  
encompasses use of  
the formulation for  
the treatment of any  
disorder described  
and claimed by the  
patent (see claims  
33-42). The claim is  
not specific to the  
treatment of  
depression.  
Page: 73  
A.  
Construction of Claims 8 and 9  
[159] The parties differ on the proper construction of Claims 8 and 9.  
[160] Pfizers position is set out in its memorandum as follows:  
1. Claims 8 and 9 clearly cover Form I ODV succinate. A patent is to be read  
purposivelyfrom the perspective of a person of ordinary skill in the art to which  
the patent relates. Purposive construction requires the Court to consider the words of  
the claims in light of the whole specification. While the words of the patent govern,  
the Court must consider the context in which they appear. The construction should be  
one that is in the interest of fairness both to the patentee and the public.”  
2. Claims 8 and 9 clearly relate to a particular crystalline compound, Form I ODV  
succinate. Claim 8 covers a compound that exhibits an x-ray diffraction pattern  
having seven characteristic peaks. The only such form disclosed in the patent is Form  
I ODV (mono) succinate (the product of Example 7). Similarly, claim 9 makes  
reference to Form I through its characteristic DSC endotherm provided on page 8.  
3. Apotexs experts argue that claims 8 and 9 are not limited to crystal Form I, but can  
be read to cover a potential class - any real or imagined compound that exhibits the  
listed XRPD peaks. This open-ended view is wrong and does not reflect an informed,  
purposive reading of the patent. It is also contrary to Apotexs NOA where it stated  
that a skilled person would understand claims 8 and 9 to relate to Form I ODV  
succinate.The proper view, as reflected in the NOA, is that a skilled person  
reviewing the 668 Patent would readily recognize the list of peaks set out in claim 8  
and the endotherm set out in claim 9 to be the characteristic data provided for crystal  
Form I ODV succinate. In fact, there is no evidence of any other crystal form of any  
compound that exhibits this characteristic data.  
[161] Apotex says in its memorandum:  
17.  
Claim 8: This is a claim for crystalline ODV-S (including  
hydrates) which exhibits the specific XRPD peaks set out in the  
claim. The claim does not contain any other limitations.  
18.  
Pfizer argues that claim 8 relates exclusively to ODV-S  
Form I because it has the same XRPD peaks as the disclosure  
reports for Form I (ground). This is an impermissible approach.  
 
Page: 74  
When a compound is characterized by an XRPD pattern in a claim,  
it is improper to use the disclosure to characterize it differently.  
19.  
Further, claim 8 includes multiple crystal forms, namely  
monohydrates and other hydrates, as is clear in the claims it  
depends upon. And the patents Form 1is not characterized by  
the XRPD of claim 8: the patent teaches that Form I (unground)  
has distinct XRPD peaks.9  
20.  
Claim 9: This is a claim for a crystalline form of ODV-S  
that has an endotherm at about 131°C. Endothermcan be  
thought of as a melting point measured by differential scanning  
calorimetry (DSC).”  
21.  
Pfizer asserts that claim 9 also relates exclusively to Form I  
ODV-S. Once again, this is incorrect because the claim is not  
drawn in this manner. Further, Example 1 of the patent is described  
as being (unground) Form I having a melting point(s) of 122.3 and  
139.6°C. This Form I is not within the scope of claim 9.  
22.  
Pfizer criticizes Apotexs construction of claim 9 for  
ignoring that Apotexs product is Form I and that Apotex does not  
dispute that its product falls within the scope of claim 8. This  
criticism illegitimately considers Apotexs product in its claims  
construction. Further, construing claims 8 and 9 as Form I also  
ignores the presumption in favour of applying different meanings  
to different claims. Finally, claim 9 cannot define Form I because  
the patents Form II also has a endotherm of about 131°C using  
Pfizers definition of aboutas discussed below.  
23.  
The skilled person would read aboutto indicate ± 1°C.  
Pfizer argues that aboutought to mean ± 2°C and thus claim 9  
encompasses those compounds having an endotherm falling within  
the range of 129-133°C. The patent does not support this  
definition.  
24.  
The patent defines aboutto mean generally within 10%”  
or alternatively...within an acceptable standard error of the mean.  
Neither party suggests the former definition applies to claim 9. In  
respect of the latter, the patent does not identify the standard of  
error of the mean for a DSC measurement of an endotherm, nor  
does it include data that would allow this to be calculated. The  
skilled addressee would not consider a margin of error of ± 2°C to  
be acceptable and Pfizers experts have not referenced any  
scientific literature to the contrary.13  
Page: 75  
25.  
Further, construing the term aboutto mean ± 2°C results  
in Form II, with its endotherm at 127°C, falling within the scope of  
claim 9, directly contrary to Pfizers construction that claim 9  
embraces only Form I. Pfizer denigration of this point as  
technicalis actually an acknowledgment that it is correct.14  
Construing a claim in a way that is consistent with the inventors’  
intentions is not `technical; it is what the Supreme Court directs.  
26.  
Pfizer retreats to an argument about the sufficiency of  
Apotexs NOA. Pfizer asserts that Apotexs expertsopinion that  
claims 8 and 9 embrace multiple compounds is contrary to the  
NOAs statement that the skilled person would understand claims  
8 and 9 to relate to Form I [ODV]-S.In fact, there is no  
contradiction.  
27.  
The NOA does not say that the scope of claims 8 and 9 is  
limited to a single compound and the allegations of overbreadth  
and insufficiency specifically assert that claims 8 and 9 include  
more than a single compound.16 The NOA asserts non-  
infringement of claim 9 (but not claim 8), making it clear that the  
NOA distinguished the subject matter of the two claims. This  
Court has rejected arguments regarding the sufficiency of the NOA  
that were based on reading a single sentence of the NOA in  
isolation from the rest of the document.”  
28.  
In any event, Pfizers experts addressed the scope of the  
claims in chief, indicating that Pfizer had fair notice of this issue.  
Even if it were otherwise, experts are permitted to diverge from  
allegations made in a Notice of Allegation, and courts are free to  
differ from either or both parties on issues of construction.  
[162] In my view, Claims 8 and 9 cover the crystalline Form I ODV succinate. I accept that  
both Claims 8 and 9 clearly relate to a particular crystalline compound, Form I ODV succinate.  
Claim 8 covers a compound that exhibits an x-ray diffraction pattern [XRPD] having seven  
characteristic peaks. The only such form disclosed in the 668 Patent is the crystalline Form I  
ODV (mono) succinate (the product of Example 7). Similarly, Claim 9 makes reference to Form  
I through its characteristic DSC endotherm provided on page 8 of the 668 Patent.  
Page: 76  
[163] The identifier XRPD set out in Claim 8 refers to Form I ODV succinate; there is no other  
formthat could have that XRPD data and fall within the claim. I find that this construction  
gives effect to the intention of the inventor and does so in the context of the patent as a whole  
regarding the crystalline Form IODV succinate.  
[164] Apotex disagrees. At page 8 of the 668 Patent the inventors state: [F]orm 1 of ODV  
succinate has an XRPD pattern substantially identical to that shown in Figures 1 (ground Form I)  
and 7 (unground Form I).At page 25 the 668 Patent states that: [W]ithout being bound by any  
theory, the inventors theorize that the XRPD for the unground crystals differed from that of the  
ground crystals due to the preferred orientation of the unground crystals.Apotex says that  
Claims 8 and 9 do not cover Form I ODV-S (unground), and in large part base this on the  
evidence of Dr. Steed. In my view this is not the proper construction of either Claims 8 or 9. First  
of all, neither Claims 8 nor 9 exclude the unground Form I. Secondly, Apotexs Dr. Steed in his  
original affidavit did not deny the inventorstheory concerning orientation of the unground  
crystals: his evidence was that the skilled person would have reservationswith it. Further,  
Pfizers Dr. Atwood filed a reply affidavit that directly and very specifically addresses  
Dr. Steeds point and did so through the eyes of the skilled person. Dr. Atwood stated that:  
4.  
Specifically, in paragraphs 158-159, Professor Steed states  
that the differences in the peak listings provided for the XRPD  
diffractograms of Figure 1 and Figure 7 exhibit differences in their  
2θ values that cannot be the result of preferred orientation effects  
in the unground sample (Figure 7) and must mean that the  
materials are different. However, Professor Steed relies on the lists  
of characteristicpeaks the patent provides for each of these  
samples in Tables 1 and 6 to suggest that the peak positions are  
different. These lists of characteristicpeaks do not include all of  
the peaks present in either diffractogram and are not intended to be  
Page: 77  
exhaustive. It is not correct to compare one against the other in  
order to look for differences or similarities in the peak positions.  
Indeed, as Professor Steed notes, preferred orientation effects can  
change the height (intensity) of the peaks in a XRPD  
diffractogram, which means that different peaks may appear to be  
characteristicin the ground sample as compared to the unground  
sample.  
5.  
A comparison of Figures 1 and 7 reveals that despite some  
differences in intensities that Figure 7 exhibits all of the seven  
characteristic peaks of Form I (peaks appear at around 10.20 2θ,  
14.91 2θ, 20.56 2θ, 22.13 2θ, 23.71 2θ, 24.60 2θ and 25.79 2θ).  
More tellingly, it does not exhibit any additional significant  
peak(s) aside from those that appear in the XRPD diffractogram  
provided in Figure 1. In my opinion, these two XRPD  
diffractograms clearly represent the same form and I believe a  
person of ordinary skill in the art would reach the same conclusion.  
[Emphasis added]  
[165] Dr. Steed filed a sur-reply affidavit in which he buttressed his position that the ground  
and unground versions of Form I are different materials. However, I on a balance of  
probabilities, I accept Dr. Atwoods evidence that the two XRPD diffractograms clearly  
represent the same form and I believe a person of ordinary skill in the art would reach the same  
conclusion.”  
[166] In addition, and this speaks to the construction of both Claims 8 and 9, Apotex stated in  
its Notice of Allegation that: [t]he skilled person would understand that Claims 8 and 9 to relate  
to Form I desvenlafaxine succinate.In my view that statement reflects the intention of the  
inventors; in my view their intentions should be given effect through a construction that holds  
that the two XRPD diffractograms represent the same form, namely the crystalline Form I ODV  
succinate.  
Page: 78  
[167] ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
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[168] In the circumstances, in my view the proper construction of Claim 8 is that it covers  
Form I ODV (mono) succinate monohydrate (i.e., the crystalline form of ODV succinate, which  
exhibits the characteristic XRPD peaks of Figure 1). In my view, this construction gives effect to  
the intention of the inventor and does so in the context of the patent as a whole.  
[169] As to Claim 9, in addition to what I have stated and found regarding Claim 8, in my view  
this claim refers to another identifier, namely an endotherm (melting point). In my view, this  
claim also refers to the crystalline Form I ODV succinate. I am supported in arriving at this  
conclusion by Apotexs Notice of Allegation which appears to concede the point where it states,  
in material part, that a skilled person would understand claims 8 and 9 to relate to Form I ODV  
desvenlafaxine succinatei.e. the crystalline Form I ODV succinate.  
[170] The parties dispute the margin of error referred to in Claim 9. Claim 9 claims [A]  
compound according to claim 6 having an endotherm at about 131°C. The key word is about.  
Pfizer argues that aboutmeans ± 2°C, therefore Claim 9 encompasses those compounds having  
an endotherm falling within the range of 129-133°C. Apotex says it means ± 1°C, narrowing the  
range to 130 to132°C.  
Page: 79  
[171] The 668 Patent defines the word aboutunder the heading Definitionson page 4:  
The termabout generally means within 10%, preferably within 5%, and more preferably  
within 1% of a given value or range. Alternatively, the termabout means within an acceptable  
standard error of the mean, when considered by one of ordinary skill in the art.”  
[172] However, I do not accept this definition applies to endotherms - if it did, then at one end  
of the numerical margins of error it would be ± 13, i.e., a 26°C variation which is far too great a  
difference to have been intended by the inventors. Therefore, and in my view as a matter of  
construction, the definition turns on the alternate, namely an acceptable standard error of the  
mean, when considered by one of ordinary skill in the art.”  
[173] The experts disagreed. Both Pfizers experts, Drs. Myerson and Atwood, considered this  
definition and opined that the margin of error for such endotherms is up to ±2°C. Apotexs  
Dr. Steed while stating that the definition in the 668 Patent was ambiguous, proceeded to review  
the 668 Patent for claim differentiation and concluded that aboutmeant ±1°C. Apotexs  
approach presents a serious difficulty in that the issue is not claims differentiation but the margin  
of error for this sort of measurement as seen by the Skilled Person. In this respect, I prefer the  
evidence of Drs. Myerson and Atwood which directly addressed the question as understood by  
the Skilled Person. Dr. Steed provided a much less satisfactory answer which in effect did not  
speak to the Skilled Persons appreciation of the margin of error for DSC measurements in terms  
of the state of the art for this sort of measurement, but very differently provided a case-specific  
analysis in which the answer depends how claims in this patent - or by extension, some other  
Page: 80  
patent - may be differentiated. In my view Dr. Steed did not answer the question in terms of the  
state of the art as well as did Drs. Myerson and Atwood. I should note that I arrived at this  
conclusion without regard to Pfizers argument based on the fact that Apotexs own proposed  
new drug submission also speaks to a margin of error of ±2°C.  
[174] I agree with Apotex that if the margin of error is ±2°C, Claim 12 also will be captured by  
Claim 9 and vice versa. However, in my view the inventors did not intend Claims 9 and 12 to  
encompass both Forms I and II. In my view, the presumption of different meanings for different  
claims is displaced; the intention of the inventors was to describe the same compound by  
reference to the different identifiers set out in both Claims 8 and 9. In my view Claims 8 and 9  
should be construed to identify the same crystalline form, namely the crystalline Form I ODV  
succinate.  
[175] Therefore I construe Claim 9 to covers Form I ODV (mono) succinate monohydrate (i.e.,  
the crystalline form of ODV succinate, which exhibits a characteristic endotherm at about 131°C  
(+ 2°C)).  
[176] Again, this construction gives effect to the intention of the inventor and does so in the  
context of the patent as a whole regarding the crystalline Form I ODV succinate referred to on  
page 8 of the 668 Patent.  
Page: 81  
B.  
Construction of Claim 33  
[177] Apotex says that the only debate between the parties relates to the scope of Claims 8 and  
9 upon which claim 33 is dependent. Therefore I construe Claim 33 as it depends on Claims 8 or  
9, use of Form I ODV succinate for the treatment of depression.  
C.  
Construction of Claims 43 and 44  
[178] Apotex says that by specifying that the use will lowerside effects, the claim makes a  
comparison to a dosage form which does not limit the blood plasma level to 225 ng/ml or less;  
that the claim is not specific to crystal form, nor to any specific blood plasma level below  
225 ng/ml; and notes with respect to the comparator, Pfizers experts proposed an instant release  
formulation.  
[179] To recall, this is the claim to the sustained release oral dosage form.I agree that the  
claim as worded does not refer to specific crystal form, but consistent with my findings  
respecting the intention of the inventors and the purpose of the 668 Patent respecting claims 8  
and 9, the claim should be construed with respect to the crystalline Form I ODV succinate. The  
other points made by Apotex should not be incorporated into the construction of this claim.  
[180] In my view Claim 43 should be construed as follows: as it depends on Claims 8 or 9, use  
of a sustained release oral dosage form comprising Form I ODV succinate to induce an average  
   
Page: 82  
blood plasma level of no more than 225 ng/ml to lower the overall incidence of the specified side  
effects as compared to oral administration of ODV succinate not so formulated.  
[181] Regarding Claim 44, Apotex says in its claims construction arguments that this claim is  
for an sustained release formulation containing ODV-S providing peak serum levels of up to 225  
ng/ml (i.e., from 0 to 225 ng/ml), and that this claim is not limited to oral formulations or to any  
particular form of ODV-S. I agree that this claim is not limited to oral formulations or to any  
particular form of ODV-S, but I see no need to add that to the claim construction as a matter of  
law.  
[182] Therefore, Claim 44 should be construed as follows: a sustained release formulation  
comprising O-desmethyl-venlafaxine succinate (in any form, including Form I ODV succinate)  
which provides average peak serum levels of up to 225 ng/ml.  
3.  
Non-infringement  
[183] I will deal with this issue claim by claim.  
[184] Claim 8: Pfizer asserts that both of Apotexs 50 mg and 100 mg products infringe  
Claim 8. Apotex made no allegation of non-infringement with respect to Claim 8 except on the  
basis that Claim 8 is invalid and therefore cannot be infringed.  
 
Page: 83  
[185] Because I have found on a balance of probabilities that Apotexs allegations relating to  
the invalidity of Claim 8 are not justified, I find on a balance of probabilities that Apotexs  
allegation of non-infringement of Claim 8 is not justified.  
[186] Claim 9: Pfizer asserts that both of Apotexs 50 and 100 mg products infringe Claim 9.  
Apotex defends on the bases that (1) Apotexs products irrespective of dosage do not fall within  
the scope of this claim and (2) that Claim 9 is invalid and cannot be infringed.  
[187] Apotexs allegation of non-infringement relating to Claim 9, other than that depending on  
a finding that Claim 9 is invalid, is based on the meaning of aboutwhich I have just discussed  
under Claims Construction, above. Apotex says that if the Court accepts Apotexs construction  
of about 131°C(namely, 130°C to 132°C) , Apotexs proposed product as set out in its new  
drug submission, which has a melting point below 130°C, does not infringe Claim 9 and  
therefore Apotexs allegation would be justified in this respect. The converse is also true, namely  
that if the Court accepts Pfizers construction of about 131°C, Apotexs proposed product will  
infringe.  
[188] I have found that the proper construction of Claim 9 entails a margin of error is ±2°C,  
producing a range of endotherms between 129°C and 133°C.  
[189] According to Apotexs Dr. Steed, the endotherms of the API in Apotexs proposed new  
drug exhibited endotherms at 129.33°C, 129.18°C, 129.34°C, and 128.96°C.  
Page: 84  
[190] Therefore I find on a balance of probabilities that Apotexs products irrespective of  
dosage fall within the scope of Claim 9. I have also found on a balance of probabilities that  
Apotexs allegations relating to the invalidity of Claim 8 are not justified. I find on a balance of  
probabilities that Apotexs allegation of non-infringement of Claim 9 is not justified.  
[191] Claim 33: Pfizer asserts that both of Apotexs 50 mg and 100 mg products infringe  
Claim 33. Apotex made no allegation of infringement with respect to Claim 33 except on the  
basis that Claim 33 is invalid and therefore cannot be infringed.  
[192] Because I have found on a balance of probabilities that Apotexs allegations relating to  
the invalidity of Claim 33 are not justified, I find on a balance of probabilities that Apotexs  
allegation of non-infringement of Claim 33 is not justified  
[193] Claims 43 and 44: Pfizer only asserts that Apotexs 50 mg product would infringe  
Claims 43 and 44. Pfizer does not dispute that Apotexs proposed 100 mg product will not  
infringe Claims 43 and 44. Apotex defends on the basis that Claims 43and 44 are invalid and  
thus cannot be infringed by its 50 mg product.  
[194] Because I have found on a balance of probabilities that Apotexs allegations relating to  
the invalidity of Claims 43 and 44 are not justified, I find on a balance of probabilities that  
Apotexs allegation of non-infringement by its 50 mg product of Claim 43 and 44 is not justified.  
Page: 85  
[195] I find on a balance of probabilities that Apotexs allegation of non-infringement by its  
100 mg product of Claims 43 and 44 is justified.  
[196] A patentee will prevail even if only one claim of a patent is found to have been infringed:  
Hughes & Woodey on Patents, LexisNexis, loose leaf 2017, vol. 1, para 38 citing to Arctic  
Cat Inc v Bombardier Recreational Products Inc, 2016 FC 1047 at para 211. In this case I have  
found that Apotexs proposed product will infringe several of the claims in the 668 Patent.  
[197] Therefore I conclude on a balance of probabilities that Pfizer has established that  
Apotexs allegation of non-infringement is not justified.  
4.  
Obviousness  
A.  
Introductory comments and summary  
[198] Pursuant to s 28.3 of the Patent Act, an invention must not be obvious to a Skilled  
Person:  
Invention must not be  
obvious  
Objet non evident  
28.3 The subject-matter  
defined by a claim in an  
application for a patent in  
28.3 Lobjet que définit la  
revendication dune demande  
de brevet ne doit pas, à la date  
Canada must be subject-matter de la revendication, être  
that would not have been  
obvious on the claim date to a  
person skilled in the art or  
science to which it pertains,  
having regard to  
évident pour une personne  
versée dans lart ou la science  
dont relève lobjet, eu égard à  
toute communication :  
(a) information disclosed more a) qui a été faite, plus dun an  
   
Page: 86  
than one year before the filing avant la date de dépôt de la  
date by the applicant, or by a  
person who obtained  
demande, par le demandeur ou  
un tiers ayant obtenu de lui  
linformation à cet égard de  
façon directe ou autrement, de  
manière telle quelle est  
knowledge, directly or  
indirectly, from the applicant  
in such a manner that the  
information became available  
to the public in Canada or  
elsewhere; and  
devenue accessible au public  
au Canada ou ailleurs;  
(b) information disclosed  
before the claim date by a  
person not mentioned in  
b) qui a été faite par toute autre  
personne avant la date de la  
revendication de manière telle  
paragraph (a) in such a manner quelle est devenue accessible  
that the information became  
available to the public in  
Canada or elsewhere.  
[Emphasis added.]  
au public au Canada ou  
ailleurs.  
[Soulignement ajouté.]  
[199] One of the central issues in this case is obviousness, and its ancillary doctrine, obvious to  
try. Once the appropriate legal tests are resolved, the determination of both obviousness and  
obvious to try resolve into factual determinations based on the evidence and the 668 Patent. I  
have concluded that viewed through the eyes of the Skilled Person, the invention claimed in the  
668 Patent, and in particular the inventive concepts of Claims 8, 9, 33, 43 and 44 were not  
obvious and were not obvious to try.  
[200] In my view, the new composition of matter being the crystalline Form I ODV succinate,  
was worth a try. In addition, there were possibilitiesthat the Skilled Person would find the  
invention claimed in the 668 Patent through difficult experimentation particularly in respect of  
crystallization and polymorph screening. However, mere possibilities are not enough, and it is  
established that being worth a tryis not the test for obvious to try.  
Page: 87  
[201] On the evidence, I have concluded that Pfizer has established on a balance of  
probabilities that Apotexs allegation of obviousness including obvious to try are not justified.  
B.  
Legal principles in the obviousness inquiry and the Sanofi decision  
[202] The key decision in the law of obviousness is that of the Supreme Court of Canada in  
Apotex Inc v Sanofi Synthelabo Inc 2008 SCC 61 [Sanofi or Plavix].  
[203] That said, after the hearing of this case, the Supreme Court gave judgment in  
AstraZeneca Canada Inc v Apotex Inc, 2017 SCC 36 [AstraZeneca], dealing with the Promise  
Doctrine. In post-hearing filings on the impact of AstraZeneca (which I will discuss in detail  
under the heading of inutility), Apotex argued that the law of obviousness was changed by  
AstraZeneca. I am not persuaded; had the Supreme Court intended to restate the law of  
obviousness in AstraZeneca it could have done so and said do but it did not. It does not appear to  
me that the Supreme Court intended to opine on obviousness when dealing with the utility  
arguments it addressed in AstraZeneca. While the obviousness inquiry starts with the claims, it is  
trite law that claims are to be read with a view to the patent as a whole. That the Court must  
identify the inventive concept of the claimin question or if that cannot readily be done,  
construe it, is demanded at the second step of the Sanofi inquiry, as I will address shortly.  
Nothing in AstraZeneca says that different claims may not have different inventive concepts, and  
indeed the Supreme Court of Canada said that it is possible for each claim in a patent to disclose  
a separate invention: Teva Canada Ltd v Pfizer Canada Inc, 2012 SCC 60 at para 64. Claims  
construction allows the Court to read the claim in the context of the patent as a whole, including  
 
Page: 88  
the description and other claims, and the disclosure may be considered to assist in understanding  
the claims or to dispel ambiguity.  
[204] Therefore, as indicated, I prefer to rely on Sanofi for the law of obviousness.  
[205] For convenience of reference and because of its centrality on this issue, I will set out in  
its entirety the relevant part of the Sanofi decision both in terms of the legal test and its  
application to the facts, per Rothstein J. for the unanimous Court:  
(d) Approach to Obviousness in Canada  
[64] While I do not think the list is exhaustive, the factors set  
forth by Kitchin J. and adopted by Lord Hoffmann in Lundbeck,  
referred to at para. 59 of these reasons, are useful guides in  
deciding whether a particular step was obvious to try. However,  
the obvious to trytest must be approached cautiously. It is only  
one factor to assist in the obviousness inquiry. It is not a panacea  
for alleged infringers. The patent system is intended to provide an  
economic encouragement for research and development. It is well  
known that this is particularly important in the field of  
pharmaceuticals and biotechnology.  
[65] In Saint-Gobain PAM SA v. Fusion Provida Ltd., [2005]  
EWCA Civ 177 (BAILII), Jacob L.J. stated, at para. 35:  
Mere possible inclusion of something within a  
research programme on the basis you will find out  
more and something might turn up is not enough. If  
it were otherwise there would be few inventions that  
were patentable. The only research which would be  
worthwhile (because of the prospect of protection)  
would be into areas totally devoid of prospect. The  
obvious to trytest really only works where it is  
more-or-less self-evident that what is being tested  
ought to work.  
Page: 89  
In General Tire, Sachs L.J. said, at p. 497:  
Obviousis, after all, a much-used word and it  
does not seem to us that there is any need to go  
beyond the primary dictionary meaning of very  
plain.  
In Intellectual Property Law, at p. 136, Professor Vaver also  
equates obviousto very plain. I am of the opinion that the  
obvious to trytest will work only where it is very plain or, to use  
the words of Jacob L.J., more or less self-evident that what is being  
tested ought to work.  
[66] For a finding that an invention was obvious to try, there  
must be evidence to convince a judge on a balance of probabilities  
that it was more or less self-evident to try to obtain the invention.  
Mere possibility that something might turn up is not enough.  
[67] It will be useful in an obviousness inquiry to follow the  
four-step approach first outlined by Oliver L.J. in Windsurfing  
International Inc. v. Tabur Marine (Great Britain) Ltd., [1985]  
R.P.C. 59 (C.A.). This approach should bring better structure to the  
obviousness inquiry and more objectivity and clarity to the  
analysis. The Windsurfing approach was recently updated by Jacob  
L.J. in Pozzoli SPA v. BDMO SA, [2007] F.S.R. 37 (p. 872), [2007]  
EWCA Civ 588, at para. 23:  
In the result I would restate the Windsurfing questions thus:  
(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 artand the inventive concept of the  
claim or the claim as construed;  
Page: 90  
(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 added in original]  
It will be at the fourth step of the Windsurfing/Pozzoli approach to  
obviousness that the issue of obvious to trywill arise.  
i.  
When Is the Obvious to TryTest  
Appropriate?  
[68] In areas of endeavour where advances are often won by  
experimentation, an obvious to trytest 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 trytest  
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 TryConsiderations  
[69] If an obvious to trytest 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?  
[70] Another important factor may arise from considering the  
actual course of conduct which culminated in the making of the  
Page: 91  
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.  
[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.  
(e) Application to the Facts of This Case  
[72] Applying the four steps of Windsurfing/Pozzoli, I accept  
the applications judges findings of fact where they are unaffected  
by his rejection of the obvious to trytest. Where application of  
the obvious to try test requires further consideration of the  
evidence, it will be necessary for this Court to make some findings  
of fact. In this case, I think it is preferable to remitting the matter to  
the trial judge for redetermination and subjecting his decision to  
further possible appeals.  
[73] Apotex filed its notice of allegation in 2002. It is now some  
six years later. If the 777 patent is invalid, and provided all other  
requirements are met, Apotex should be entitled to a notice of  
compliance from the Minister without any further delay. Indeed,  
the NOC Regulations are intended to be a summary procedure. I  
Page: 92  
think it is time that this matter finally be resolved. I would conduct  
the following analysis:  
i.  
Identify the Notional Person Skilled in the  
Art  
[74] Both parties agreed that a trained pharmachemist is that  
person.  
ii.  
Identify the Relevant Common General  
Knowledge of That Person  
[75] Apotex reiterates its submissions made with respect to  
anticipation, insisting that, since the methods of separation were  
well known, the claimed invention and its advantages would have  
been obvious to the person skilled in the art. Shore J. found on the  
evidence before him that there were five well-known methods to  
separate this racemate into its isomers. However, he did not find  
that the relative advantage of the dextro-rotatory isomer would  
have been known by the skilled person.  
iii.  
Identify the Inventive Concept of the Claim  
in Question or, if That Cannot Readily Be Done,  
Construe It  
[76] The construction of the claims in the 777 patent is not an  
issue. It is agreed that they constitute the dextro-rotatory isomer of  
the racemate and its pharmaceutically acceptable salts and  
processes for obtaining them.  
[77] The inventive concept of the claims is not readily  
discernable from the claims themselves. A bare chemical formula  
in a patent claim may not be sufficient to determine its  
inventiveness. In such cases, I think it must be acceptable to read  
the specification in the patent to determine the inventive concept of  
the claims. Of course, it is not permissible to read the specification  
in order to construe the claims more narrowly or widely than the  
text will allow.  
[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.  
Page: 93  
iv.  
Identify What if Any Differences Exist  
Between the 875 Patent and the 777 Patent  
[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.  
v.  
Viewed Without Any Knowledge of the  
777 Patent, Do Those Differences Constitute Steps  
Which Would Have Been Obvious to the Person  
Skilled in the Art or Do They Require a Degree of  
Inventiveness?  
[81] At this stage, it must be determined whether the nature of  
the invention in this case is such as to warrant an obvious to try”  
test. The discovery of the dextro-rotary isomer and its bisulfate salt  
came after experimentation. There were interrelated variables with  
which Mr. Badorc had to experiment. An obvious to trytest in  
this case would recognize the evidence of the expert witnesses as  
to the discovery of the beneficial properties of the dextro-rotary  
isomer and its bisulfate salt and the methods for finding them.  
[82] The applications judge cannot be faulted for the analysis he  
conducted as far as it went. However, he erred in not allowing for  
the application of the obvious to trytest, which is warranted in  
this case.  
[83] The following factors are therefore relevant at this fourth  
step of the obviousness inquiry:  
Page: 94  
(1)  
Is It More or Less Self-Evident That What Is  
Being Tried Ought to Work?  
[84] As I have observed earlier, Shore J. found that the skilled  
person would not know, before separating this particular racemate  
into its isomers and then testing the separated isomers, that the  
properties of the dextro rotatory isomer would be different from  
the properties of the racemate or the levo rotatory isomer (para.  
81). Similarly, he found that the person skilled in the art would not  
know before trying the different salts in combination with the  
dextro rotatory isomer what the bisulfate salts beneficial  
properties would be (para. 82).  
[85] Just because there are known methods of separating a  
racemate into its isomers does not mean that a person skilled in the  
art would necessarily apply them. The fact that there are such  
known methods of separation will be of no account if the evidence  
does not prove that it was more or less self-evident to try them. It  
is true that at the relevant time there was evidence that a skilled  
person would know that the properties of a racemate and its  
isomers might be different. However, a possibility of finding the  
invention is not enough. The invention must be self-evident from  
the prior art and common general knowledge in order to satisfy the  
obvious to trytest. That is not the evidence in this case.  
(2)  
What Is the Extent, Nature and Amount of  
Effort Required to Achieve the Invention?  
[86] As indicated, the applications judge found that there were  
five well-known techniques for separating this racemate into its  
isomers. He also found that there was no evidence that at the  
relevant time, a person skilled in the art would know which one  
would work with the racemate at issue in this case. The evidence  
was that a skilled person would eventually find the right technique.  
[87] As earlier indicated, Shore J. also found that there was no  
evidence that at the relevant time a person skilled in the art would  
know before separating the racemate and testing the isomers what  
their properties would be, although the specific properties of the  
isomers could be discovered. There was evidence that, using  
known techniques, the properties of different pharmaceutically  
acceptable salts to be used with the dextro-rotatory isomer could be  
discovered.  
Page: 95  
[88] However, in considering whether it was obvious to tryto  
find the invention, once it was decided to isolate the dextro-  
rotatory isomer, the methods for doing so were known, the  
methods for testing the properties of the isomers were known and  
the method for determining the beneficial properties of the salts to  
be used with the isomer would also have been known.  
[89] According to Mr. Badorcs affidavit, it took from  
November 1985 to April 1986 to find the 777 invention, and he  
was already familiar with the 875 invention. Potentially five  
different methods to separate the racemate would have had to have  
been tried and tested before determining the properties of the  
dextro-rotatory isomer. As in the case of anticipation, one might  
infer that the applications judge, if asked to decide this question,  
would have held that the investigation here was not routine, but  
rather was prolonged and arduous. In any event, on the facts of this  
case, this factor would assume small significance in view of the  
finding I make with respect to the whole course of conduct  
discussed at para. 91 below.  
(3)  
Is There a Motive From the Prior Art to Find  
the Solution That the 777 Patent Addresses?  
[90] It is well known that the pharmaceutical industry is  
intensely competitive. Market participants are continuously in  
search of new and improved medications and want to reach the  
market with them as soon as possible. So demand for an effective  
and non-toxic product to inhibit platelet aggregation might be  
assumed to exist. However, nothing in the 875 patent or common  
general knowledge provided a specific motivation for the skilled  
person to pursue the 777 invention. The prior patent was a genus  
patent, and selection might be expected. However, the prior patent  
did not differentiate between the efficacy and the toxicity of any of  
the compounds it covered. This suggests that what to select or omit  
was not then self-evident to the person skilled in the art.  
(4)  
What Is the Course of Conduct Which Was  
Followed Which Culminated in the Making of the  
Invention?  
[91] Mr. Badorcs affidavit reveals that for several years prior to  
November 1985, Sanofi was in the process of developing the  
racemate in its salified form. In November 1985, the racemate was  
being tested in preliminary human clinical trials. It was at that time  
that Mr. Badorc was asked to separate the racemate into its  
Page: 96  
isomers. After he discovered that the dextro-rotatory isomer was  
active and non-toxic and that the levo-rotatory isomer was non-  
active and toxic, Sanofi decided to develop the dextro-rotatory  
isomer and abandon its work on the racemate. However, this was  
after it had spent millions of dollars and several years developing  
[the racemate] up to the point of preliminary human clinical trials”  
without at least trying to see if the dextro rotatory isomer had  
advantageous properties to those of the racemate (Affidavit of Mr.  
Badorc, at para. 25). This evidence was uncontradicted.  
(5)  
Was the Invention of the 777 Patent  
Obvious to Try?  
[92] The methods to obtain the invention of the 777 patent were  
common general knowledge. It can be assumed that there was a  
motive to find a non-toxic efficacious product to inhibit platelet  
aggregation in the blood. However, it was not self-evident from the  
875 patent or common general knowledge what the properties of  
the dextro-rotatory isomer of this racemate would be or what the  
bisulfate salts beneficial properties would be and therefore that  
what was being tried ought to work. The course of conduct and the  
time involved throughout demonstrate that the advantage of the  
dextro-rotatory isomer was not quickly or easily predictable. Had  
the dextro-rotatory isomer been obvious to try, it is difficult to  
believe that Sanofi would not have opted for it before unnecessary  
time and investment were spent on the racemate. I conclude that  
the prior art and common general knowledge of persons skilled in  
the art at the relevant time were not sufficient for it to be more or  
less self-evident to try to find the dextro-rotatory isomer.  
(f) Conclusion on Obviousness  
[93] As I have earlier explained, there was a significant  
difference between the 875 genus patent and the 777 selection  
patent. The difference was not obvious. Having regard to the  
foregoing analysis, I conclude that the allegation of obviousness is  
not justified.  
[Emphasis added except where in original.]  
Page: 97  
[206] The Supreme Court in Sanofi made new patent law for Canada; the Supreme Court held  
there may be circumstances where an obvious to try analysis could be conducted - previously,  
obvious to try was not allowed as a test of obviousness.  
[207] I note that the Supreme Court in Sanofi provided guidance concerning obvious to try at  
the outset of its analysis:  
[64] However, the obvious to trytest must be approached  
cautiously. It is only one factor to assist in the obviousness inquiry.  
It is not a panacea for alleged infringers. The patent system is  
intended to provide an economic encouragement for research and  
development. It is well known that this is particularly important in  
the field of pharmaceuticals and biotechnology.  
[65] Mere possible inclusion of something within a research  
programme on the basis you will find out more and something  
might turn up is not enough. If it were otherwise there would be  
few inventions that were patentable. The only research which  
would be worthwhile (because of the prospect of protection) would  
be into areas totally devoid of prospect. The obvious to trytest  
really only works where it is more-or-less self-evident that what is  
being tested ought to work.  
I am of the opinion that the obvious to trytest will work only  
where it is very plain or, to use the words of Jacob L.J., more or  
less self-evident that what is being tested ought to work.  
[66] For a finding that an invention was obvious to try, there  
must be evidence to convince a judge on a balance of probabilities  
that it was more or less self-evident to try to obtain the invention.  
Mere possibility that something might turn up is not enough.  
[208] According to Sanofi’s guidance, obvious to try must be approached cautiously.The  
obvious to try test “…is only one factor to assist in the obviousness inquiry.” The Supreme Court  
Page: 98  
added that obvious to try “… is not a panacea for alleged infringers.” The Supreme Court added  
relevant context to these principles in para 64: [T]he patent system is intended to provide an  
economic encouragement for research and development. It is well known that this is particularly  
important in the field of pharmaceuticals and biotechnology.”  
[209] In the next paragraph, para 65, the Supreme Court confirmed that: [M]ere possible  
inclusion of something within a research programme on the basis you will find out more and  
something might turn up is not enough. If it were otherwise there would be few inventions that  
were patentable. The only research which would be worthwhile (because of the prospect of  
protection) would be into areas totally devoid of prospect. The obvious to trytest really only  
works where it is more-or-less self-evident that what is being tested ought to work.”  
[210] It recapped these parameters in para 66 stating: [F]or a finding that an invention was  
obvious to try, there must be evidence to convince a judge on a balance of probabilities that it  
was more or less self-evident to try to obtain the invention. Mere possibility that something  
might turn up is not enough.”  
C.  
Federal Court of Appeal jurisprudence including Atazanavir and Beloit  
[211] The Federal Court of Appeal addressed the obvious to try analysis in several cases after  
Sanofi.  
 
Page: 99  
[212] In Pfizer v Apotex, 2009 FCA 8, the Federal Court of Appeal per Noël J.A. rejected the  
proposition, advanced on the basis of English law, that if the prior art indicates that something  
may work, and the motivation is such as to make this avenue worthwhileto pursue, the  
obvious to try test is satisfied:  
[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 worthwhileto  
pursue (Pfizer Ltd., supra, para. 107, as quoted at para. 42 above).  
As such, a solution may be worthwhileto pursue even though it  
is not obvious to tryor 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.  
[Emphasis added.]  
[213] In Novartis, after referring to Sanofi, Justice Hughes discusses the Federal Court of  
Appeals decision in Sanofi-Aventis v Apotex Inc, 2013 FCA 186 [Plavix 2]:  
[64] These principles have been applied recently by the Federal  
Court of Appeal in Sanofi-Aventis v Apotex Inc, 2013 FCA 186,  
wherein the Court of Appeal found that the Trial Judge had erred  
in concluding that if the necessary techniques were available to  
arrive at the alleged invention, the invention itself was obvious.  
Pelletier JA (with whom Noël JA agreed) wrote at paragraphs 73  
and 74:  
73  
With these facts in mind, the Supreme Court  
articulated why the separation of the racemate was  
not obvious to try. It held that just because the  
methods of separating a racemate into its isomers  
are known, it does not follow that a person skilled  
in the art would necessarily apply them. The  
Supreme Court explained:  
It is true that at the relevant time there was evidence  
that a skilled person would know that the properties  
Page: 100  
of a racemate and its isomers might be different.  
However, a possibility of finding the invention is  
not enough. The invention must be self-evident from  
the prior art and common general knowledge in  
order to satisfy the obvious to trytest. That is not  
the evidence in this case.  
Plavix, cited above, at paragraph 85  
However, the prior patent did not differentiate  
between the efficacy and the toxicity of any of the  
compounds it covered. This suggests that what to  
select or omit was not then self-evident to the  
person skilled in the art.  
Plavix, cited above, at paragraph 90:  
74  
What emerges from this review of the  
Supreme Courts decision in Plavix, cited above, is  
that the key factor in its obvious to tryanalysis  
was the lack of knowledge of the properties of the  
enantiomers of the compounds of the 875 Patent,  
including the racemate from which clopidogrel was  
obtained. Absent that knowledge, it was not obvious  
to try to resolve the racemate, or any other  
compound, so as to obtain the enantiomer having  
those advantageous properties.  
[Emphasis added.]  
[214] In Eli Lilly v Mylan, 2015 FCA 286, per Dawson J.A., the Federal Court of Appeal at  
para. 4, declined to agree that the obvious to try test should be whether the skilled person had  
good reason to pursue predictable solutions or solutions that provide a fair expectation of  
success”‘. Instead, the Court of Appeal at para. 4 stated that: “…. the correct test, and the test  
that ought to be applied by the Federal Court, is that articulated by the Supreme Court of Canada  
in Apotex Inc v Sanofi-Synthelabo Canada Inc, 2008 SCC 61, [2008] 3 SCR 265, at para 66: For  
a finding that an invention was obvious to try, there must be evidence to convince a judge on a  
Page: 101  
balance of probabilities that it was more or less self-evident to try to obtain the invention. Mere  
possibility that something might turn up is not enough.”  
[215] Shortly before the hearing in the case at bar, the Federal Court of Appeal released Bristol-  
Myers Squibb Canada Co v Teva Canada Limited, 2017 FCA 76 [Atazanavir]. The parties  
included references to Atazanavir in their submissions.  
[216] In Atazanavir, per Pelletier J.A., the Federal Court of Appeal considered the obviousness  
inquiry and the doctrine of obvious to try. The Court of Appeal confirmed that the innovative  
feature of the Supreme Courts decision in Sanofi in relation to obviousness was its adoption of  
the obvious to trytest [para 34].  
[217] At para 38 the Court said that “… the Supreme Court was quick to add that the obvious  
to trytest must be approached cautiouslybecause it is only one factor to assist in the  
obviousness inquiry: Plavix 1 at para. 64.”  
[218] The Federal Court of Appeal confirmed that:  
[60] The reasonable conclusion to be drawn from these  
expressions of caution is that the obvious to trytest has not  
displaced all other inquiries into obviousness. Indeed, that is what  
this Court concluded in Wenzel Downhole Tools Ltd. v. National-  
Oilwell Canada Ltd., 2012 FCA 333, [2014] 2 F.C.R. 459 at  
para. 105.  
Page: 102  
[219] In this connection the Federal Court of Appeal in Atanazavir also referred to the test for  
obviousness prior to Plavix which test had been set out by the Federal Court of Appeal in Beloit  
Canada Ltd v Valmet OY (1986), 64 N.R. 287, 8 C.P.R. (3d) 289 at 294 (FCA) [Beloit]:  
61.  
While the Supreme Court accepted the obvious to trytest  
as a way of addressing the issue of obviousness, other inquiries  
remain possible, including the Beloit test, subject to the Courts  
warnings about a rigid acontextualapplication of that test, or of  
any other for that matter.  
[220] The Beloit test referred in Atanazavir set out the previous established obviousness test:  
The classical touchstone for obviousness is the technician skilled  
in the art but having no scintilla of inventiveness or imagination; a  
paragon of deduction and dexterity, wholly devoid of intuition; a  
triumph of the left hemisphere over the right. The question to be  
asked is whether this mythical creature (the man in the Clapham  
omnibus of patent law) would, in the light of the state of the art  
and of common general knowledge as at the claimed date of  
invention, have come directly and without difficulty to the solution  
taught by the patent.  
[221] The Federal Court of Appeal held that Sanofi did not the change the definition of  
obviousness:  
[65] It may be helpful to keep in mind that the obviousness  
analysis asks whether the distance between two points in the  
development of the art can be bridged by the Skilled Person using  
only the common general knowledge available to such a person. If  
so, it is obvious. The first of those points is the state of the prior art  
at the relevant date. References in the jurisprudence to the  
inventive concept, the solution taught by the patent, what is  
claimedor simply the inventionare attempts to define the  
second point.  
[66] Prior to Plavix 1, the jurisprudence followed Beloit and  
treated the second point as the solution taught by the patent”  
which was often treated as synonymous with what is claimed in  
Page: 103  
the patentor the invention: Proctor & Gamble Pharmaceuticals  
Canada Inc. v. Canada (Minister of Health), 2004 FCA 393,  
[2005] 2 F.C.R. 269 at para. 47, Pfizer Canada Inc. v. Canada  
(Health), 2007 FCA 209, 366 N.R. 347 at para. 133, Novopharm  
Limited v. Janssen-Ortho Inc., 2007 FCA 217, 366 N.R. 290 at  
para. 25. The question is whether the inventive conceptwas  
intended to redefine the second point as it was understood to be  
prior to Plavix 1. I note that in the passage from Pozzoli quoted  
above, the English Court of Appeal did not consider the inventive  
conceptto have changed anything of substance. If the parties  
could not agree on it, it could be forgotten. It went on to say at  
paragraph 19 of its reasons: In the end what matters is/are the  
difference(s) between what is claimed and the prior art.This is  
essentially the state of Canadian law prior to Plavix 1.  
[67] Is it the case that changing one of the two points I referred  
to earlier amounts to changing the definition of obviousness?  
Given that obviousness is concerned with whether bridging the  
difference between the prior art and a second point requires  
inventiveness, changing the second point will affect the difficulty  
of bridging that difference, therefore making inventiveness more or  
less likely. If that is so, is it reasonable to conclude that the  
Supreme Court intended to change the definition of the  
obviousness analysis when it adopted, without commentary, the  
Windsurfing/Pozzoli framework? Is it likely that the Supreme  
Court, having taken great care in modifying the test for  
obviousness, would, without saying so, change the definition of  
obviousness?  
[68] My inclination is to believe that the Supreme Court does  
not change substantive law by implication, particularly when it has  
shown a cautious approach to change in the same context: see  
Apotex Inc. v. Eli Lilly Canada Inc., 2016 FCA 267, 142 C.P.R.  
(4th) 171 at para. 37.  
[Emphasis added.]  
[222] In Atanazavi, the Federal Court of Appeal clarified the definition of inventive concept”  
(and see in this respect para 65 just quoted above):  
[75] For the reasons set out above, I find that the inventive  
conceptis not materially different from the solution taught by  
Page: 104  
the patent. Had the Federal Court applied that definition to the  
facts, it would have found that the inventive concept in this case is  
atazanavir bisulfate, a salt of atazanavir which is pharmaceutically  
acceptable because it has equal or better bioavailability than the  
atazanavir free base. Atazanavirs limited bioavailability was the  
source of the motivation to pursue the solution. The fact that claim  
2 of the 736 patent claims a pharmaceutical dosage form of Type-  
I atazanavir bisulfate confirms its acceptability for pharmaceutical  
purposes.  
D.  
Analysis of Obviousness  
[223] With these principles in mind, I proceed with the analysis of obviousness as set out by the  
Supreme Court in Sanofi.  
1. (a) Identify the notional person skilled in the art”  
[224] A patent is addressed to the Person of Ordinary Skill in the Art[Skilled Person], who I  
previously defined in the following terms:  
[38] A patent is addressed to this notional Skilled Person, who is  
unimaginative and uninventive, but at the same time is understood  
to have an ordinary level of competence and knowledge incidental  
to the field to which the patent relates and to be reasonably diligent  
in keeping up with advances: AstraZeneca Canada Inc v Apotex  
Inc, 2014 FC 638 at para 51 (citing Merck & Co v Pharmascience  
Inc, 2010 FC 510 at paras 34-40), affd 2015 FCA 158. The  
unimaginative and uninventivelanguage is found in Beloit  
Canada Ltd v Valmet OY (1986), 8 C.P.R. (3d) 289 (F.C.A.)  
[Beloit], where the Federal Court of Appeal refers to the  
unimaginative skilled technician, and Apotex Inc v Sanofi-  
Synthelabo Canada Inc, 2008 SCC 61 at para 81, where the  
Supreme Court refers to inventiveness as foreign to the Skilled  
Person in the obviousness analysis. In my view, the Federal Court  
retained these concepts in its interpretation of the skilled technician  
in patent law: AstraZeneca Canada Inc v Apotex Inc, 2014 FC 638  
   
Page: 105  
at para 51 (Rennie, J as he then was) (citing Merck & Co v  
Pharmascience Inc, 2010 FC 510 at paras 34-40 (Hughes, J)), affd  
2015 FCA 158 (Dawson, J.A.).  
Gilead Sciences, Inc v Canada (Health), 2016 FC 856.  
[225] In this case, the parties take the following positions on the qualities of the Skilled Person,  
which would in this case be a person or team of people:  
Pfizers position: The 668 patent is directed to those skilled in the arts of solid state  
chemistry, pharmaceutical formulation and development, pharmacology and  
pharmacokinetics.  
Apotexs position: The 668 patent addresses solid state chemistry, pharmaceutical  
formulation and development, pharmacology, pharmacokinetics, and the treatment of  
disease and conditions. By definition the skilled addressee would have skills in these  
areas.  
[226] I take it as a given that a Skilled Person has skills in their respective areas. Therefore, the  
parties disagree only on whether the Skilled Person would have skills in the treatment of disease  
and conditions, which is what Apotex says; Pfizer disagrees. However, Apotexs Dr. Parr agreed  
that the 668 Patent is not necessarily directed to a medical doctor, and added that  
pharmaceutical scientists understand that their purpose is to formulate an active ingredient in a  
way that allows it to be both therapeutically effectively and safe when used in a clinical setting.  
In cross-examination Dr. Parr stated that a Skilled Person team without an MD was an option. In  
fact, the only expert with a medical degree (Pfizers Dr. Blier) deposed that medical expertise is  
Page: 106  
not required of the Skilled Person. Dr. Blier added that in general, medical doctors are  
concerned with the treatment of patients in a clinical setting and not with the formulation of  
drugs -- that is the work of a person of skill in pharmaceutics.I agree.  
1. (b) Identify the relevant common general knowledge of the Skilled Person  
[227] The parties disagree as to what constitutes the common general knowledge of the Skilled  
Person.  
[228] In my view, as of February 2001, general methods and techniques to make salts and  
crystals and prepare sustained release dosage forms were known and published. The skilled  
person would also know that ODV had been disclosed to be an active metabolite of venlafaxine  
and a member of a class of compounds in several patents including the US 186, WO 551 and CA  
540. And they would know that ODV was useful to treat depression. The prior art disclosed  
ODV both as a free base and a fumarate salt, and the Skilled Person would know that other  
pharmaceutically acceptable salts (including succinate, among at least eleven (11) others as set  
out in US 186 at column 2, ll. 35 and following; the same eleven were identified in CA 540; WO  
851 listed twenty-six other pharmaceutically acceptable non-toxic acids that might be reacted to  
form salts of ODV.  
[229] However, Pfizer is correct in stating that while the prior art explicitly disclosed ODV as a  
free base and a fumarate salt, and ODV succinate as a potential salt, no crystal form of that salt  
let alone the crystalline Form I ODV succinate had ever been expressly disclosed, made or  
 
Page: 107  
characterized. Also, none of the prior art teaches the successful preparation of a succinate salt of  
ODV nor does it teach, more importantly for this case, the successful preparation of Form I ODV  
succinate, and nothing in the prior art discloses any of the properties or either ODV succinate or  
Form I ODV succinate.  
[230] In my view, the number of experiments required to move from the acceptable  
pharmaceutical salts to the Form I ODV succinate was extremely large as deposed by  
Dr. Myerson at para 102 of his affidavit, and in the nature of a research program, not routine  
experimentation. Even though a Skilled Person may have had some general expectations about  
which salts may form, these expectations were theoretical and the evidence is that empirical  
testing was required to determine if a salt could be made and only then could its properties be  
assessed. It was impossible to predict in advance which of the many possible salts, if any, would  
have the most appropriate properties for formulation as a drug in terms of stability, solubility,  
permeability and bioavailability. Much the same was known in the prior art of crystals: the  
Skilled Person would not know and could not predict which salt would crystallize, nor what  
properties the crystalline form, if any, would have. One would not know in advance that the  
succinate salt, or the crystalline Form I ODV succinate, in the language of the Sanofi test,  
would work.”  
[231] The Skilled Person also knew that even successfully forming a salt was but one part of  
the puzzle; he or she knew that to prepare pharmaceutical salts for formulation into  
pharmaceutical drugs, they were typically looking for a stable crystalline solid. However,  
Page: 108  
whether or not a particular salt formation experiment would result in crystals was not known or  
predictable. Skilled persons would not know in advance how a crystalline solid (if any) of a  
given compound could be made, how many different crystal forms of that compound might exist  
(including hydrated and solvated forms), what those forms would be, or what properties those  
forms would have. They would know that some salts might crystallize, some might form  
amorphous forms, but they would also know that other salts would neither form into crystals.  
[232] The Skilled Person would know generally of the existence of crystalline and polymorph  
screening, and as Apotexs expert put it, that crystal and polymorph screening was specialized”  
work that had to be done. As Dr. Park deposed, polymorph screening was not rote work, was  
difficult and in her experience required skill and judgment. It was not possible to predict at the  
outset of a polymorph screen how many solid forms would identified, what they would be, or  
what solid forms would result from any particular method or set of conditions. Therefore, as Dr.  
Park deposed from her experience, and Dr. Myerson deposed as an expert on the subject, this  
process often required numerous experiments and analyses, and strategy and judgment had to be  
employed to make decisions about how to proceed based on the results that we obtained such  
that the number of potential experiments that can be conducted is extremely large.  
[233] I accept what Dr. Myerson deposed in connection with both the matter of salt screens and  
the matter of crystalline and polymorph screening. Dr. Myerson was a professor of Industrial  
Pharmacy and Pharmaceutics at MIT; in my view his evidence was comprehensive and credible.  
He has what I consider to be very considerable research and academic experience in industrial  
Page: 109  
crystallization and the crystallization of pharmaceutical solids - the matters at hand in relation to  
Form I ODV succinate. His evidence in connection with the crystal and polymorph screening  
process is corroborated by the experience of Dr. Park, which I have accepted, as set out in para  
126 and following of these Reasons. I appreciate that Dr. Park is a named inventor in the 668  
Patent, but this did not detract from her evidence.  
[234] Dr. Myerson deposed:  
Choosing an Appropriate Salt  
72.  
In order to determine if a compound can form salts and if  
so to find the most appropriate salts of a given active compound  
for development, scientists will attempt to make and test a number  
of different salts and examine their properties in a process called a  
salt screen.If the active compound is a base, a salt screen will be  
directed at finding an acid that is potentially capable of forming a  
salt with that free base. Conversely, if the active compound is  
acidic, the salt screen involves finding a base that is capable of  
forming a salt with the free acid.  
73.  
During a salt screen experiment for a free base, scientists  
will dissolve the free base and a potential acidic salt former in  
solution and attempt to precipitate a salt from the mixture by  
changing the conditions of the system. These experiments involve  
using different conditions of concentration and temperature, and  
different solvents and solvent mixtures. The experiments would be  
repeated for each potential counterion (i.e., acid).  
74.  
The main purpose of the salt screen is to determine whether  
salts of the compound can be prepared with the different counter-  
ions under consideration, whether the salt formed is crystalline,  
and whether the form is stable. The choice of potential acids (or  
bases) for pharmaceutical salt formation can be large. It is not  
limited to those counterions that had been previously used in  
approved pharmaceutical products, but would include any acid  
present in food or drink that are generally regarded as safe.  
75.  
The salt selection and formation process is highly  
unpredictable. Indeed, one cannot predict prior to actually  
Page: 110  
attempting to form a salt whether the reaction of a given active  
drug compound with a particular acid or base will successfully  
produce a salt or what the properties of that salt will be.  
76.  
Once a salt form is found with a particular counterion, that  
salt is then typically subjected to a solid form (polymorph) screen,  
which consists of another set of experiments conducted over a  
variety of different conditions to determine what, if any, crystalline  
forms exist for that particular salt.  
77.  
The solid form of a particular salt form can significantly  
influence a number of physical and chemical properties of the API  
including solubility, dissolution rate, chemical stability,  
hygroscopicity, crystal shape and manufacturing/processing  
characteristics. Scientists cannot predict how the formation of a  
particular solid form of a salt will affect these properties prior to  
successful formation and analysis of the salt and its solid forms.  
Therefore, it is not possible to predict in advance of actually  
making the salt whether its formation will yield any solid form  
(crystalline or amorphous), much less one with more desirable  
properties than those of the free base or other salt forms of the  
drug.  
Crystalline and Amorphous Solids  
78.  
Crystals are solids in which the constituent atoms or  
molecules are arranged in a periodic repeating pattern that extends  
in three dimensions. When crystals are grown slowly and carefully  
they are normally bounded by plane faces (flat surfaces extending  
in different directions) that can be seen with the naked eye.  
Looking at a common material such as table salt under a  
magnifying glass will reveal these plane faces. They can also be  
seen in the beautiful mineral samples that are often displayed in  
museums.  
79.  
Not all crystalline materials display these obvious plane  
faces. Materials such as steel, concrete, bone, and teeth are made  
up of small crystals that can be seen under a light or electron  
microscope. Still other materials, such as wood, silk, hair, and  
many solid polymers (plastics) are only partially crystalline or  
have crystalline regions.  
80.  
Solids that are not crystalline and have no long range order  
for example, glass are said to be amorphous. Amorphous solids  
are often (but not always) less chemically stable than crystalline  
Page: 111  
solids (an undesirable property for pharmaceuticals). However,  
they are typically more soluble than crystalline materials (a  
desirable property for pharmaceuticals). There are a number of  
reasons why a compound might form as an amorphous solid, rather  
than a crystalline solid. One common reason is the presence of  
impurities that block the formation of the crystalline lattice  
(explained below). Materials can also be mixtures of crystalline  
and amorphous solids. For example, a sample can be largely  
amorphous with some crystalline content and vice versa.  
81.  
Crystals are made up of molecules that interact with each  
other to form chemical bonds of different kinds. They are usually  
classified as ionic, covalent, metallic, van der Waals, or hydrogen  
bonds, with the first three types being stronger than the last two.  
Organic molecules (molecules containing carbon) form crystals  
which are known as molecular crystals, in which the molecules are  
held together in the crystal form by weak attractive van der Waals  
forces.  
82.  
The internal structure of a molecular crystal, called the  
crystal structure or crystalline lattice, is determined by the position  
of the molecules relative to each other in a three dimensional  
space. Different salts of the same parent compound will have  
different crystal structures, because they will be comprised of  
different molecules.  
83.  
The process by which crystals are formed is called  
crystallization. Crystallization from solution is the most common  
crystallization method. In this method, crystallization is induced by  
changing the state of the system to reduce the solubility of the  
substance of interest. The change of state can be brought about by  
cooling, evaporation of solvent, changing of solvent composition,  
chemical reaction, or pH change. This change of state results in  
formation of a crystalline solid through processes known as  
nucleation (the birth of new crystals) and crystal growth (the  
growth of the nuclei to larger sizes).  
84.  
Nucleation of the initial crystal is unpredictable, and it is  
often difficult to crystallize a newly synthesized compound for the  
first time. Once the initial crystal is obtained, it can be used to  
seedsolutions to assist in further crystallization of the  
compound. Under certain circumstances, the nucleation step can be  
delayed almost indefinitely. For example, a solution of phenyl  
salicylate can be kept at a liquid state for several years without any  
solid form emerging out of the solution.  
Page: 112  
Polymorphism  
85.  
Some chemical species can crystallize into more than one  
three-dimensional crystal structure. This phenomenon is called  
polymorphism (or allotropism if the species is an element, such as  
carbon). While polymorphism is relatively common among organic  
molecules, whether or not a particular compound is capable of  
polymorphism and if so how many different polymorphs may  
exist cannot be predicted and must be determined empirically (to  
the extent possible to do so).  
86.  
Different polymorphs of the same material can display very  
different properties. A dramatic example is carbon, which can  
crystallize as graphite or as diamond. Properties such as hardness,  
density, electrical conductivity and shape are very different for  
these two solids although they are both crystalline. These  
significant differences in properties, brought about by differences  
in crystal structure, are not unique to carbon; they can occur in all  
materials that display polymorphism. Other properties that  
normally vary among polymorphs of a given substance include  
solubility, dissolution rate, and vapor pressure, among others.  
87.  
At a particular temperature, one polymorph will be the  
thermodynamically stable form (of the polymorphs currently  
known for a given compound). This does not mean that other  
polymorphs cannot exist under those conditions; it means only that  
one polymorph is stable and any others present can convert to the  
stable polymorphic form over time. The rate of this transition, or  
whether it occurs at all, is dependent on various conditions, such as  
temperature, pressure, presence of solvent, the relative stability of  
the crystal forms and the solubility of the polymorph(s).  
Pseudo-polymorphism  
89.  
The discussion above relating to the thermodynamic  
stability of polymorphs only applies to single component solid  
forms (true polymorphs). Another related category of solid forms  
are known as pseudo-polymorphs.  
90.  
Pseudo-polymorphism refers to the ability of certain  
compounds to crystallize in a structure that contains a solvent as  
part of the crystal lattice. These crystals are also known as  
solvates. A solvate in which the solvent is water is usually referred  
Page: 113  
to as a hydrate. For a given pseudo-polymorph, the ratio of the  
number of molecules of solvent to the number of molecules of the  
chemical species itself is usually fixed. This is referred to as its  
stoichiometry. These forms are referred to as pseudo-polymorphs  
because although they involve the same compounds, they also  
include solvent molecules as part of the structure.  
91.  
Each pseudo-polymorph of a given stoichiometry itself can  
have polymorphs, so a compound can have polymorphs of the  
compound itself (single component) and if the compound for  
example, has a monohydrate and a dihydrate form, each of these  
forms can also have polymorphs.  
92.  
Different crystal forms of an API will have different  
properties from each other and will also differ from the amorphous  
form. In addition, solvates and hydrates will also have different  
properties from other crystal forms and from each other. These  
differences in properties of solid forms can significantly impact the  
manufacturability, performance and/or quality of the drug product.  
93.  
The thermodynamic stability of a compound therefore  
becomes more complicated when looking at systems which have  
multiple polymorphs and pseudo-polymorphs (and polymorphs of  
pseudo-polymorphs). Statements about stability must include both  
the temperature and the presence of solvent. For example, in  
discussing the relative stability of hydrates to a non-hydrated form  
(or of hydrates to each other) both the temperature and the  
presence of water must be specified.  
94.  
Like the different polymorphs of a given compound, it is  
also not possible to predict in advance whether or not a compound  
may have one or more pseudo-polymorphs and if so, what those  
pseudo-polymorphs may be. Knowledge of the existence of  
polymorphs or pseudopolymorphs for one compound does not  
provide useful information about the existence of polymorphs or  
pseudopolymorphs of a different compound (even if the  
compounds are structurally similar, or are different salts of the  
same molecule).  
Importance of Polymorphs in Pharmaceutical Industry  
98.  
Changes in a compounds solid state form can result in  
significant differences in its chemical and physical characteristics.  
Page: 114  
These differences can affect the manufacturability, performance  
and/or quality of the drug product. Since many important  
pharmaceutical compounds display polymorphism and pseudo-  
polymorphism (and can therefore exist in different forms), the  
study of a compounds crystal form is extremely important in the  
pharmaceutical industry.  
99.  
One of the most well-known episodes demonstrating the  
importance of polymorphism in pharmaceuticals involves the  
antiretroviral drug ritonavir (Norvir). In 1998, after the drug had  
been approved and was on the market, a more stable, less soluble  
crystalline form appeared in the formulation that caused  
dissolution failures of the soft gelatin capsules. Because the new  
polymorph was less soluble, less of the drug was absorbed in the  
bloodstream, and the dosage form contained in the soft-gels no  
longer worked. The product was withdrawn from the market  
because the manufacturing process was no longer able to produce  
the desired polymorph reliably. The manufacturer later learned that  
the presence of a low-level impurity in the process had been  
inhibiting the formation of a more stable form. Once that impurity  
was no longer present, the more stable and less soluble form  
emerged. Eventually the product was reformulated with the more  
stable polymorph and relaunched. This demonstrates that when  
evaluating polymorph stability, you can only indicate that a given  
form is the most stable form of those discovered to date, as it is  
always possible to potentially discover a new, more stable form.  
100. In addition, the most stable form of a compound known is  
not necessarily the form that has the desired properties. The history  
of paracetamol (also known as acetaminophen) exemplifies the  
difficulties encountered in identifying the appropriate polymorph  
for pharmaceutical formulations. In the mid-1990s, Wyeth first  
attempted to use the thermodynamically stable Form I in  
pharmaceutical formulations. However, its crystal structure  
exhibited certain properties that made it extremely expensive and  
troublesome to make in an oral formulation. Other polymorphs  
were difficult to isolate and obtain in a stable form. One  
polymorph was observed only in fusion experiments, and was  
reported to be so unstable that no crystals had been isolated to date.  
The third polymorph, Form II, had been almost impossible to  
reproduce reliably for over 20 years. Wyeth spent a significant  
amount of resources to reliably crystallize Form II before realizing  
that Form II converted to Form I if allowed to remain in solution or  
stored without drying, but did not convert to Form I if it was  
Page: 115  
ground or compressed. This further illustrates how variations in  
experimental and manufacturing conditions can mask the existence  
of other polymorphs, including those which may be better suited  
for pharmaceutical formulations than the most stable polymorph  
known for the compound.  
101. Today, the search for crystalline forms, including  
polymorphs, solvates and hydrates, has become a significant part  
in the development of new pharmaceutical products. Polymorph  
screening is time consuming with no ability to predict success in  
identifying a suitable solid-state form for development. Solid form  
screening for a given compound can involve thousands of  
experiments performed over many months or even longer. There is  
no standardmethod for performing a solid form screen and the  
number of experiments and conditions that are tried are dependent  
on the choices made by the investigator and the time allotted to the  
screen.  
102. While the general methods to perform crystallizations at  
different conditions and with different solvents were known in the  
art as of the early 2000s, there are a wide variety of combinations  
of variables such as, solvents, solvent mixtures, temperatures,  
cooling rates, evaporation rates, etc. that could be used to attempt  
to generate new solid state forms. Thus, the number of potential  
experiments that can be conducted is extremely large.  
103. Overall, given a particular compound, a person skilled in  
the art in the early 2000s would not be able to predict:  
(a)  
whether he or she would be able to make  
any crystal form of that compound;  
(b)  
if so, what level of effort would be required  
to obtain it;  
(c)  
what its properties would be, including  
whether there were potential polymorphs, solvates  
and hydrates of that crystal from;  
(d)  
if there were potential polymorphs, solvates  
and hydrates, under what conditions those  
polymorphs, solvates and hydrates could be  
prepared; and  
Page: 116  
(e)  
what the properties of any polymorphs,  
solvates and hydrates would be.  
104. Therefore, even if potential solid forms are discovered,  
such forms may be unsuitable for formulation and/or manufacture  
into a drug product and therefore, unsuitable for drug development.  
Properties such as hygroscopicity, solubility, solid state stability,  
chemical stability and crystal shape (among others) can all  
influence the suitability of a solid forms.  
105. As summarized by a publication contemporary to the date  
of the 668 Patent, the relevance of polymorphism is clear but  
remains a subject that is not fully or widely understood at a  
fundamental level.The inherent unpredictability of crystalline  
solid form was acknowledged in the scientific literature:  
It is still not possible to predict with any reasonable  
level of confidence the crystal structure of an  
organic material ... The range and combinations of  
crystal growth conditions are virtually infinite, and  
there is no way to guarantee the preparation of  
additional polymorphs of a substance, much less the  
generation of allof them.  
This statement from 1993 remains true, even today. Other  
references contemporary to the 668 Patent similarly highlight the  
unpredictability of developing polymorphs.  
[Emphasis added, citations omitted.]  
[235] Given that as of 2001, neither ODV succinate nor any of its forms or properties were  
known including the Form I ODV succinate, in my respectful view, a Skilled Person could not  
have known, anticipated or predicted the properties of either ODV succinate generally, or Form I  
ODV succinate, or in particular, whether those properties would be amenable to formulation as a  
sustained release dosage form, let alone one with any specific pharmacokinetic profile.  
[236] This was not only the evidence of Pfizer, but of Apotex as well.  
Page: 117  
[237] Evidence offered by Apotexs Dr. Bastin confirmed that looking at the 186 Patent and  
Can 540 Patent, even if the Skilled Person performed a salt screen he or she would not know in  
advance which salts would be formed from the screen. Further, neither Patent gave the skilled  
person any more information about which salts of ODV could be made than the other prior art.  
Dr. Bastin likewise agreed that the 851 Patent does not identify which salts are necessarily  
referred to.  
[238] The evidence further confirmed that choosing the appropriate salt can be a very difficult  
task, which in my respectful view required judgment. Dr. Steed was referred to an article which  
stated: [C]hoosing the appropriate salt, however, can be a very difficult task, since each salt  
imparts unique properties to the parent compound.Dr. Steed was asked if that was something  
that the skilled reader would observe as being part of the art in 2001. Correct? A. Yes and the  
keyword here is choosing, that making a choice can be a difficult task because very often  
different commercial drivers, depending upon a particular way in which a medicine is to be  
sold.”  
[239] To the same effect was another article (Bighley) put to Dr. Steed, which said:  
[A]lthough attempts have been made to apply decision analysisand potential problem  
analysisto select salts and help predict salt performance [1], the choice of which salt to use  
remains a difficult decision.Dr. Steed testified:  
Q.  
That is certainly something that the skilled reader reading  
this document in 2001 would observe and make a note of. Correct?  
Page: 118  
A.  
Once again, you are referring to the choice being the  
difficulty here and in fact what this article is doing is providing, as  
he says, a decision tree to help with that choice.  
[240] It seems to me that Pfizer is correct in stating that there was no generally accepted  
procedure of selecting a salt form because each procedure is based upon the structure of each  
particular drug form.  
[241] This was confirmed by Apotexs Dr. Steed who agreed that teachings in a 1994 textbook  
was part of the prior art in 2001. The textbook stated: [Al]though the importance of using the  
optimal salt form of a compound in dosage form design is well-recognised there is no generally  
accepted procedure of selecting such a form during the drug development.Dr. Steed explained  
the meaning of this passage:  
Q.  
A.  
Have I read that correctly?  
You have, that is because each procedure is based upon the  
particular drug substance in question.  
Q.  
A.  
Q.  
I was just asking whether or not I had read it correctly?  
Your reading was accurate.  
Thank you. And this was something that a skilled person  
would have read and observed in 2001. Correct?  
A. Yes, this is part of the state of the art in 2001.  
[242] The following passage from a textbook relied upon by Dr. Steed stated: [T]his review is  
intended to provide a strategic approach to remove much of this uncertainty by presenting  
concepts and ideas in the form of flow charts rather than a set of guidelines or regulations. This  
Page: 119  
is especially important because each individual compound has its own peculiarities which require  
flexibility approach.Dr. Steed gave the following answers regarding this passage:  
Q.  
Stopping there, and a skilled reader would make note of  
that observation and statement on 2001. Correct?  
A.  
Yes, this is a 1995 article, part of the state of the art, in  
which Byrn is providing a systemic approach to addressing  
regulatory concerns over solid form.  
Q.  
Right, and he is saying that because each compound has its  
own peculiarities an investigator must use some flexibility in the  
approach. Correct?  
A.  
That is what he says, yes, and what he means by that is that  
you need to consider the actual structure of the drug substance  
itself in designing the screening.  
[243] The foregoing deals with the salts. The situation regarding crystals is, if anything more  
complex, and further from the capabilities of the unimaginative uninventive Skilled Person in my  
respectful view, based on the experience of Dr. Park which I have accepted and that of  
Dr. Myerson referred to at para 234 above. Apotexs witnesses confirm a number of points, a  
central one being the fact that identification of crystals was not predictable. Dr. Steed agreed that  
the Skilled Person in 2001 cannot predict in advance how many crystal structures of a  
compound might be stable under a given set of conditions.While he then testified that is  
possible to make predictions about how many crystal forms there might be computationally, he  
did not share any such computations in his affidavit, and later agreed that crystal structures were  
in fact not predictable. In 2009 he authored a book in which he stated that in general crystal  
structures are not predictable: [D]espite the fact that, in general, crystal structures are not  
predictable, a number of attempts, some of them increasingly successful, have been made to  
Page: 120  
address the problem from a computational standpoint.Apotexs Dr. Steed testified that: [T]he  
trick is knowing which ones of those will actually form in practice. In other words, finding the  
conditions to produce them.He confirmed that if crystal structures were generally unpredictable  
of 2009, they were also generally unpredictable to the Skilled Person as of 2001. He later  
confirmed that in 2001 the computational approach did not work in 2001, “… the field in 2001  
did not really progress by calculating a crystal structure in advance, it is much more simple to  
simply crystallise the compound and analyse its structure experimentally.”  
[244] Moreover, polymorph screening was not only difficult, but seen as time-consuming and  
expensive according to Dr. Steed who wrote in 2012 concerning crystal forms of theophylline,  
polymorphs and hydrate: [D]iscovery of the full range of crystal forms of any given compound  
is usually time-consuming and expensive, and even after extensive screening it is difficult to be  
certain that the process is complete and every possible form has been identified.Dr. Steed also  
wrote: [I]t is increasingly apparent that many compounds can exist in more than one crystal  
form, and identification and analysis of every form (particularly the thermodynamically stable  
form under a given set of conditions) is essential for manufacturing, storage, and intellectual  
property considerations.”  
[245] Apotex makes a great number of other assertions concerning what a Skilled Person would  
know of the common general knowledge. To save repetition I will deal with these under  
Question 1 of Sanofis obvious to try analysis later in these Reasons at para 300.  
Page: 121  
2.  
Identify the inventive concept of the claim in question or if that cannot readily be done,  
construe it  
[246] Identifying the inventive concept is the next step in the obviousness analysis outlined in  
Sanofi. The Federal Court of Appeal in Atanazavir held that the inventive stepis the same as  
the solution taught by the patent. In this connection, having regard to the Federal Court of  
Appeals comments concerning Beloit, and the decision of the Supreme Court in Sanofi, what is  
claimed in the patentand the inventionare synonymous with inventive stepand the  
solution taught by the patent. The solution taught by the patent, also known as the inventive  
concept is to be assessed in respect of each claim at issue (claim by claim), which emphasizes  
that different claims may have different inventive concepts.  
[247] This second point, the solution taught by the patent, also known as the inventive concept  
is to be assessed in respect of each claim (claim by claim) at issue: Sanofi at para 67. I accept  
that different claims may have different inventive concepts: Pozzoli SpA v BDMO, [2007] FSR  
37 (2007) at para 17:  
What now becomes stage (2), identifying the inventive concept,  
also needs some elaboration. As I pointed out in Unilever Pie v  
Chefaro Proprietaries Ltd [1994] R.P.C. 567 at 580:  
It is the inventive concept of the claim in question  
which must be considered, not some generalised  
concept to be derived from the specification as a  
whole. Different claims can, and generally will,  
have different inventive concepts.”  
 
Page: 122  
Apotexs Dr. Steed was instructed to the same effect; he said in cross-examination: [I] was told  
the inventive concept is to be discerned from the language of the claims with the understanding  
that the individual claims may have different inventive concepts to them, so yes, it is a claim-by-  
claim basis.Apotexs Dr. Bastin testified that novel crystalline forms are inventions above and  
beyond the identification of a salt.”  
[248] Claims 8 and 9. Both Claims 8 and 9 cover Form I ODV (mono) succinate monohydrate,  
that is, the crystalline Form I ODV succinate. Claims 8 and 9 specifically claim a new and  
distinct composition of matter. Claim 8 says this crystal form exhibits a fingerprint, namely  
characteristic XRPD as set out in Figure 1, while Claim 9 identifies another fingerprint namely  
that the polymorph crystal exhibits a characteristic endotherm (melting point) at about 131?C. In  
my view, these identification or characterization data, which are inherent to the form of the novel  
crystal at issue, are not the invention. These identifying properties are not the inventive concept,  
nor are they the solution taught by the 688 Patent.  
[249] In my respectful view, the solution taught by these two claims, heir inventive concept, is  
the novel crystalline form of ODV succinate referred to as Form I. In short, the inventive concept  
or the solution taught by these two claims in the 668 Patent is the novel crystal Form I ODV  
succinate.  
[250] Apotex disagrees and says the 668 Patent teaches that the solution to this problem is  
ODV succinate in any form, and further that ODV succinate is the single inventive concept of  
Page: 123  
the claims. With respect, I am unable to agree. It is well established that in construing the claims  
one must read the patent as a whole, a point Apotexs Dr. Steed conceded. However, Dr. Steed,  
who advanced the single inventive concept in connection with all asserted claims, did not discuss  
the following statement in the 668 Patent itself, which says at page 5, that [E]ach polymorph  
forms another aspect of the invention.Dr. Steed agreed, however, that by this statement in the  
668 Patent, the inventors are clearly telling the reader that polymorphic forms would be  
different aspects of the invention.Apotexs Dr. Parr in cross-examination on the same statement  
in the 668 Patent, agreed with the proposition that:  
Q.  
[B]y another,when it says, another aspect of the  
invention,it means an aspect of the invention in addition to the  
invention of the novel salt?  
A.  
Yes, maam.  
[251] Based on this evidence and the clear language of the statement in the 668 Patent that  
[E]ach polymorph forms another aspect of the invention, I am confirmed in my view that the  
inventive concept or the solution taught by these two claims in the 668 Patent is the novel crystal  
Form I ODV succinate. I also reject Apotexs single inventive concept argument.  
[252] Claim 33. Claim 33 depends on Claims 8 and 9. Claim 33 states: [U]se of an effective  
amount of O-desmethyl-venlafaxine succinate or a mixed salt thereof as claimed in any one  
claims 1 to 20 for the treatment of depression.This is a use claim, and in the context of this  
litigation, is a claim to the use of an effective amount of Form I ODV (mono) succinate  
Page: 124  
monohydrate that is, to the use of an effective amount of the crystalline Form I ODV succinate  
for the treatment of depression.  
[253] Therefore, the inventive concept or solution taught by claim 33 is the use of an effective  
amount of the crystalline Form I ODV (mono) succinate monohydrate for the treatment of  
depression.  
[254] I have rejected the single inventive concept argument.  
[255] Claim 43. Claim 43 is expressed: [U]se of therapeutically effective amount of sustained  
release oral dosage form comprising O-desmethyl;-venlafaxine succinate or a mixed salt thereof  
as claimed in any one of claims 1 to 20 prepared in a dosage to induce a blood plasma level no  
more than 225 ng/ml to lower the incidence of nausea, vomiting, diarrhea, abdominal pain,  
headache, vaso-vagal malaise, or trismus resulting from the oral administration of O-desmethyl-  
venlafaxine succinate.Properly construed, this claim means: as it depends on claims 8 or 9, use  
of a sustained release oral dosage form comprising Form I ODV succinate to induce an average  
blood plasma level of no more than 225 ng/ml to lower the overall incidence of the specified side  
effects as compared to oral administration of ODV succinate not so formulated.  
[256] The inventive concept of claims 43 and 44 is a sustained release dosage form comprising  
the new crystalline Form I ODV succinate that has specific pharmacokinetic characteristics  
namely a peak blood plasma level of less than 225 ng/ml and, and therefore reduces the  
Page: 125  
incidence of certain side effects that would otherwise result from oral administration of ODV  
succinate.  
[257] I have rejected the single inventive concept argument.  
[258] Claim 44. Claim 44 is made as follows: [A] sustained release formulation comprising  
O-desmethyl-venlafaxine succinate and a pharmaceutically acceptable carrier or excipient,  
wherein the sustained release formulation provides peak serum levels of up to 225ng/ml.I have  
construed it as a sustained release formulation comprising O-desmethyl-venlafaxine succinate (in  
any form, including Form I ODV succinate) which provides average peak serum levels of up to  
225 ng/ml.  
[259] In my respectful opinion, the inventive concept and solution taught by the invention in  
claim 44 is a sustained release formulation comprising O-desmethyl-venlafaxine succinate (in  
any form, including Form I ODV succinate) which provides average peak serum levels up to  
225 ng/ml.  
[260] Taken together, the inventive concept of Claims 43 and 44 is a sustained dosage form  
comprising the novel salt, ODV succinate (or Form I ODV succinate, as those claims depend on  
Claims 8 or 9) that has specific pharmacokinetic characteristics (a peak blood plasma level of  
less than 225 ng/ml), and therefore reduces the incidence of certain side effects that would  
otherwise result from oral administration of ODV succinate. The difference between the two is  
Page: 126  
that Claim 43 refers to lowering the incidence of adverse side effects while Claim 44 does not;  
both reference a peak blood plasma level of less than 225 ng/ml.  
[261] I have already rejected the single inventive concept argument.  
3.  
Identify what, if any, differences exist between the matter cited as forming part of the  
state of the artand the inventive concept of the claim or the claim as construed.  
[262] I will take this stage of the analysis on a claim by claim basis.  
i.  
Claims 8 and 9  
[263] In my respectful view, the Skilled Person would not know nor could he or she predict that  
ODV succinate salt would form as a solid, whether that solid would form as a crystal, or what the  
properties of a hypothetical crystalline solid would be. This is the case regardless of the fact that  
salt screens were generally known as were, also in general terms, crystallization and polymorph  
screens. In fact, neither ODV succinate nor any of its crystalline forms, let alone Form I, were  
specifically previously disclosed in the prior art.  
[264] The solution taught by Claims 8 and 9, their inventive concept, is the novel crystalline  
form of ODV succinate referred to as Form I. In short, the inventive concept or the solution  
taught by the 668 Patent is the novel crystal Form I ODV succinate.  
   
Page: 127  
[265] In my view therefore the gap between the state of the art and the inventive concept of  
Claims 8 and 9 of the 668 Patent is therefore the invention of a new composition of matter  
namely Form I ODV succinate.  
ii.  
Claim 33  
[266] To recall, the inventive concept or solution taught by Claim 33 is the use of an effective  
amount of the crystalline Form I ODV (mono) succinate monohydrate for the treatment of  
depression. Claim 33 depends on Claims 8 and 9.  
[267] Pfizer says that because the prior art did not disclose the Form I ODV succinate or for  
that matter, any of its properties, the gap between the prior art and invention of Claim 33, the use  
of this novel crystalline form for the treatment of depression, was not obvious. I agree.  
[268] For the same reasons that Form I ODV succinate was not more or less self-evident, in my  
view, neither was its use to treat depression.  
[269] The gap between the state of the art and the inventive concept of Claim 33 of the 668  
Patent is therefore the invention of a new composition of matter namely Form I ODV succinate  
to treat depression.  
 
Page: 128  
iii.  
Claim 43 and 44  
[270] In terms of Claims 43 and 44, both depend on Claims 8 and 9 i.e., the new crystalline  
Form I ODV succinate. To recall, the inventive concept of Claims 43 and 44 is a sustained  
dosage form comprising Form I ODV succinate, as those claims depend on Claims 8 or 9, that  
has specific pharmacokinetic characteristics namely a peak blood plasma level of less than  
225 ng/ml.  
[271] Claim 43 in addition to the foregoing, claims a reduction in side effects over the oral  
administration of Form I ODV succinate in an immediate release formulation; both reference a  
peak blood plasma level of less than 225 ng/ml. Claim 44 does not refer to side effects.  
[272] Pfizer says that the gap between the prior art and Claims 43 and 44 is the invention of a  
new sustained release dosage form of the novel salt or crystalline form that reduces blood plasma  
levels of ODV and reduces the incidence of adverse events from non-sustained release  
administration. With respect, I agree.  
[273] I have found that neither ODV succinate nor any of its forms or properties were known,  
predicted or predictable. The Skilled Person could not anticipate what properties either ODV  
succinate or Form I ODV succinate would have, which means that the Skilled Person could not  
anticipate whether those properties would allow the formulation of a sustained release dosage.  
 
Page: 129  
As with Claim 33, the prior art also taught and the Skilled Person knew that every new solid  
form had its own set of unknown, unpredicted and unpredictable properties.  
[274] In addition, for the same reasons that Form I was not more or less self-evident, neither  
was its use in sustained release formulation. Likewise it cannot be said that the use of Form I  
ODV succinate in sustained release formulation was more or less self-evident to reduce adverse  
side effects.  
[275] While the prior art disclosed that sustained release formulations of other drugs including  
EFFEXOR XR had been both made and used to ameliorate blood plasma concentrations  
generated by immediate release administration, the prior art contained no application of this  
general principle to ODV, nor to ODV succinate nor to Form I ODV succinate. The evidence  
establishes that it would not have been obvious to the Skilled Person that ODV succinate had any  
stable, solid crystal form at all, let alone one that could be formulated into a sustained release  
formulation. Nor was it obvious or predicted or predictable that Form IODV succinate would  
have the appropriate stability, solubility, permeability and bioavailability characteristics for oral  
formulation development as identified by the experimentation entailed in its development. It was  
not known, predicted or predictable that any such sustained release formulation of ODV  
succinate would result in blood plasma levels below 225 ng/ml while maintaining therapeutic  
concentrations as per both Claims 43 and 44.  
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?  
 
Page: 130  
5.  
Apply the definition of obvious before Sanofi  
[276] At this point in the analysis, in light of Atanzavir and instead of moving next to an  
obvious to tryanalysis, I will apply the test for obviousness set out by the Federal Court of  
Appeal in Beloit.  
[277] Thus, the question becomes whether the Skilled Person would, in the light of the state of  
the art and of common general knowledge as at the claimed date of invention, have come directly  
and without difficulty to the solution taught by the patent, namely directly and without difficulty  
to the novel crystalline form of ODV succinate referred to as Form I. In my respectful view, the  
evidence does not justify such a conclusion.  
[278] I appreciate Apotex’s arguments to the effect that its witnesses were blinded, but that is a  
question of relevance, reliability and weight: Gilead Sciences, Inc v Canada (Health), 2016 FC  
857 at para 59, and see the cases discussed there. I have already accepted and prefer the  
evidence of Dr. Myerson on the common general knowledge regarding the matters of salt screens  
and crystalline and polymorph screening as set out above at paras 234 and 278 of these reasons. I  
have also accepted the experience-based evidence of Dr. Park in this connection, see para 124  
and following, which corroborates that of Dr. Myerson. Dr. Myerson concluded:  
102. While the general methods to perform crystallizations at  
different conditions and with different solvents were known in the  
art as of the early 2000s, there are a wide variety of combinations  
of variables such as, solvents, solvent mixtures, temperatures,  
cooling rates, evaporation rates, etc. that could be used to attempt  
 
Page: 131  
to generate new solid state forms. Thus, the number of potential  
experiments that can be conducted is extremely large.  
103. Overall, given a particular compound, a person skilled in  
the art in the early 2000s would not be able to predict:  
(a)  
whether he or she would be able to make  
any crystal form of that compound;  
(b)  
if so, what level of effort would be required  
to obtain it;  
(c)  
what its properties would be, including  
whether there were potential polymorphs, solvates  
and hydrates of that crystal from;  
(d)  
if there were potential polymorphs, solvates  
and hydrates, under what conditions those  
polymorphs, solvates and hydrates could be  
prepared; and  
(e)  
what the properties of any polymorphs,  
solvates and hydrates would be.  
104. Therefore, even if potential solid forms are discovered,  
such forms may be unsuitable for formulation and/or manufacture  
into a drug product and therefore, unsuitable for drug development.  
Properties such as hygroscopicity, solubility, solid state stability,  
chemical stability and crystal shape (among others) can all  
influence the suitability of a solid forms.  
105. As summarized by a publication contemporary to the date  
of the 668 Patent, the relevance of polymorphism is clear but  
remains a subject that is not fully or widely understood at a  
fundamental level.The inherent unpredictability of crystalline  
solid form was acknowledged in the scientific literature:  
It is still not possible to predict with any reasonable  
level of confidence the crystal structure of an  
organic material ... The range and combinations of  
crystal growth conditions are virtually infinite, and  
there is no way to guarantee the preparation of  
additional polymorphs of a substance, much less the  
generation of allof them.  
Page: 132  
This statement from 1993 remains true, even today. Other  
references contemporary to the 668 Patent similarly highlight the  
unpredictability of developing polymorphs.  
[Emphasis added, citations omitted.]  
[279] In these circumstances, and in my respectful view, the Skilled Person in the light of the  
state of the art and of common general knowledge as at the claimed date of invention, would not  
have come directly and without difficulty to the solution taught by the 668 Patent, namely the  
novel crystalline form of ODV succinate referred to as Form I.  
[280] The test in Beloit is whether the Skilled Person would in the light of the state of the art  
and of common general knowledge as at the claimed date of invention, have come directly and  
without difficulty to the solution taught by the patent.This test is not met on the facts of this  
case. Further, the road seen by the Skilled Person based on the prior art would be difficult and  
not direct. The Skilled Person would foresee an extremely large number of studies and tests with  
no predictable result.  
[281] In essence the Skilled Person would see a research program. This finding applies to  
Claims 8 and 9. As they are dependent on Claims 8 and 9, this finding applies also to Claims 33,  
43 and 44.  
[282] The obviousness inquiry does not end here. At this point, having looked at obviousness  
using the Beloit test, the Court must follow the balance of the steps suggested by Sanofi. The  
Page: 133  
Court must now consider the applicability of, and if appropriate, review the matter against the  
obvious to trytest.  
6.  
Consider the doctrine of obvious to try  
[283] As the Supreme Court noted at para 67 of Sanofi, [I]t will be at the fourth step of the  
Windsurfing/Pozzoli approach to obviousness that the issue of obvious to trywill arise.”  
Having said that the Supreme Court asked at para 68: When Is the Obvious to TryTest  
Appropriate?In answer it said at para 68: [I]n areas of endeavour where advances are often  
won by experimentation, an obvious to trytest 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 trytest since there may be many  
chemically similar structures that can elicit different biological responses and offer the potential  
for significant therapeutic advances.”  
[284] This case is one in the pharmaceutical industrycategory; therefore the next step is to  
consider the factors discussed by the Supreme Court in Sanofi, recognizing that they are not  
exhaustive.  
[285] In doing so, I note the introductory guidance set out in Sanofi at para 64: [H]owever, the  
obvious to trytest must be approached cautiously. It is only one factor to assist in the  
obviousness inquiry. It is not a panacea for alleged infringers. The patent system is intended to  
provide an economic encouragement for research and development. It is well known that this is  
 
Page: 134  
particularly important in the field of pharmaceuticals and biotechnology.These were described  
as useful guidanceby the Federal Court of Appeal in Apotex Inc v Pfizer Canada Inc, 2009  
FCA 8 at para 26.  
[286] These Reasons will consider the obvious to try analysis first without reference to this  
guidance, and then come back to it to determine what if any difference this guidance makes to  
the analysis; in the manner proposed it will be easier to determine the impact of this guidance on  
the Courts conclusions.  
[287] After establishing this guidance in Sanofi, the Supreme Court set out factors that should  
be considered:  
[69] If an obvious to trytest 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?  
[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  
Page: 135  
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.  
[288] I will deal with each of these considerations.  
7.  
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?  
[289] The parties disagree. Both parties cited cases where, on the accepted evidence in a  
particular case, various courts came to conclusions on obvious to try. While of relevance, each  
case in this connection has been decided on facts particular to it, having regard to the  
submissions of the experts and counsel. Although Apotex pressed hard, it remains that none say  
that all salt screens are obvious to try, or involve only matters of routine experimentation. Nor do  
any say that all polymorph or crystal screen research is obvious to try or merely entails routine  
experimentation. None do and of course none could. Ultimately the proper characterization of  
each case is a question of applying the law of obvious to try as set out in Sanofi to the evidence  
before the Court.  
[290] Pfizer says that all the experts agree that the existence and properties of crystal forms  
cannot be predicted in advance of their having been successfully made and tested. A Skilled  
Person would not know nor could he or she predict that Form I ODV succinate existed nor could  
 
Page: 136  
they identify or predict what properties it would have, or how if at all, it could be prepared. In  
my respectful view this is an accurate summary.  
[291] I agree with that summary because it is borne out in the extract from the affidavit of  
Dr. Myerson set out at paras 234 and 278 of these Reasons, whose evidence was corroborated by  
the experience of Dr. Park as set out at para 124 and following of these Reasons. Dr. Myerson  
concluded with respect to the crystallization and polymorph screening, with apologies for  
repetition:  
103. Overall, given a particular compound, a person skilled in  
the art in the early 2000s would not be able to predict:  
(a)  
whether he or she would be able to make  
any crystal form of that compound;  
(b)  
if so, what level of effort would be required  
to obtain it;  
(c)  
what its properties would be, including  
whether there were potential polymorphs, solvates  
and hydrates of that crystal from;  
(d)  
if there were potential polymorphs, solvates  
and hydrates, under what conditions those  
polymorphs, solvates and hydrates could be  
prepared; and  
(e)  
what the properties of any polymorphs,  
solvates and hydrates would be  
104. Therefore, even if potential solid forms are discovered,  
such forms may be unsuitable for formulation and/or manufacture  
into a drug product and therefore, unsuitable for drug development.  
Properties such as hygroscopicity, solubility, solid state stability,  
chemical stability and crystal shape (among others) can all  
influence the suitability of a solid form.  
Page: 137  
105. As summarized by a publication contemporary to the date  
of the 668 Patent, the relevance of polymorphism is clear but  
remains a subject that is not fully or widely understood at a  
fundamental level.The inherent unpredictability of crystalline  
solid form was acknowledged in the scientific literature:  
It is still not possible to predict with any reasonable  
level of confidence the crystal structure of an  
organic material ... The range and combinations of  
crystal growth conditions are virtually infinite, and  
there is no way to guarantee the preparation of  
additional polymorphs of a substance, much less the  
generation of allof them.  
[292] The second part of this question asks whether there are a finite number of identified  
predictable solutionsknown to persons skilled in the art; in my view there were not because the  
number of potential experiments was in fact extreme large. That was the evidence of  
Dr. Myerson which I accept who deposed that the number of potential experiments that can be  
conducted is extremely large:  
80.  
Today, the research for crystalline forms, including  
polymorphs, solvates and hydrates, has become a significant part  
in the development of new pharmaceutical products. Polymorph  
screening is time consuming with no ability to predict success in  
identifying a suitable solid-state form for development. Solid form  
screening for a given compound can involve thousands of  
experiments performed over many months or even longer. There is  
no standardmethod for performing a solid form screen and the  
number of experiments and conditions that are tried are depending  
on the choices made by the investigator and the time allotted to the  
screen.  
81.  
While the general methods to perform crystallizations at  
different conditions and with different solvents were known in the  
art as of the early 2000s, there are a wide variety of combinations  
of variables such as, solvents, solvent mixtures, temperatures,  
cooling rates, evaporation rates, etc. that could be used to attempt  
to generate new solid state forms. Thus, the number of potential  
experiments that can be conducted is extremely large.  
Page: 138  
[Emphasis added.]  
[293] This fact was confirmed by Dr. Parks experience who deposed at para 34 of her affidavit  
that SSCI typically conducted a large number of different experiments under a wide variety of  
conditions in order to try to identify as many different solid state forms as possible.”  
[294] I also note the Supreme Court in Sanofi poses the question as one concerning identified  
predictable solutions. While there were research possibilities, and the possibility of conducting  
studies and engaging in a research program, on the facts of this case, there were no identified  
predictable solutions.  
[295] Apotex argues that salt screens and crystallization and polymorph screening constituted  
routine experimentation known to the Skilled Person, and that knowledge together with a large  
number of other factors alleged to be known to the Skilled Person made it more or less self-  
evident that Form I ODV succinate, i.e., what was being tried, ought to work.  
[296] Routine experimentation is permitted under the obvious to try analysis. The issue of  
routine experimentation was recognized by the Federal Court of Appeal in Plavix 2 at para 81,  
and is referenced in Sanofi itself under the second question in obvious to try. I disagree with the  
position advanced by Apotex because in my view far more than routine experimentation would  
have been foreseen by the Skilled Person in this case. A general knowledge of salt screens and  
what was known of crystallization and polymorph screening, merely provided possibilities for  
Page: 139  
the Skilled Person to conduct research, studies and further experiments which in this case were  
significant and in the nature of a research program particularly in the area of crystallization and  
polymorph screening. This is not enough; every Court that has reviewed this matter has agreed  
that mere possibilities do not satisfy the obvious to try set out in Sanofi.  
[297] In my view, the fact of certain known tests and procedures in this case is very analogous  
to the facts before the Supreme Court in Sanofi, where the second person advanced similar  
arguments that were rejected. The Court in rejecting those arguments, said:  
[85] Just because there are known methods of separating a  
racemate into its isomers does not mean that a person skilled in the  
art would necessarily apply them. The fact that there are such  
known methods of separation will be of no account if the evidence  
does not prove that it was more or less self-evident to try them. It  
is true that at the relevant time there was evidence that a skilled  
person would know that the properties of a racemate and its  
isomers might be different. However, a possibility of finding the  
invention is not enough. The invention must be self-evident from  
the prior art and common general knowledge in order to satisfy the  
obvious to trytest. That is not the evidence in this case.  
[Emphasis added.]  
[298] In my respectful view this is the situation here: salt screens and the availability of  
crystallization and polymorph screening were generally known as methods by which it might be  
possible to screen for salts, which may or may not solidify, with any such resulting salts having  
unknown and unpredictable properties. It was also known to the Skilled Person that through salt  
screens and crystallization and polymorph screening research programs it might be possible to  
identify crystals and polymorphs. However the Skilled Person would also know that no such  
Page: 140  
crystal or polymorph forms might be possible, and that if any crystals or polymorphs were found,  
they would have unknown and unpredictable properties. In my view that does not make the  
inventive concept of the Claims 8 and 9, namely, Form I ODV succinate, obvious to try. The  
evidence in this case established what were mere possibilities of identifying the ODV succinate  
salt, or perhaps no salt at all, in a salt screen in first place, and a possibility of finding Form I  
ODV succinate crystalline, or perhaps no crystalline form at all, in crystallization and polymorph  
screening in the second place. But mere possibilities are not sufficient.  
[299] As Sanofi put it, knowing these procedures existed is of no account because the evidence  
does not prove it was more or less self-evident to try them: a possibility of finding the invention  
is not enough. The invention must be self-evident from the prior art and common general  
knowledge in order to satisfy the obvious to trytest. That is not the evidence in this case.”  
[para 85] That is not the evidence in this case either: the invention was not self-evident from the  
prior art and the common general knowledge on the facts of this case.  
[300] Apotex argued that the Skilled Person would have knowledge of numerous other matters,  
which taken together would have led him or her to the solution taught by the 668 Patent,  
i.e., Form I ODV succinate. I will attempt to list them, followed by my observations:  
A. The skilled person knew that the properties of medicinal compounds were typically  
improved by forming salts. Court comment: it was known that some compounds  
might form salts while others might not and that if salts formed they might entail  
improved properties. That was a hoped for result.  
Page: 141  
B. Further, ODV had been the subject of previous patents, which patents taught and  
claimed salts (and solvates) of ODV generally. Court comment: I agree.  
C. It was known that such salts typically crystallize into one or more different solid  
forms, each one having somewhat different pharmaceutical properties. Court  
comment: I disagree: crystallization was not a certainty, some might crystalize, some  
might form into amorphous forms, and some may do neither. ||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
D. For example, ODV-S, as a salt, would be expected to be more soluble than ODV free  
base, and generally speaking, increased solubility was correlated with increased oral  
bioavailability. Court comment: I disagree because this result was not known or  
predicted and required testing and experimentation.  
E. The skilled person knew that changing the form (i. e. salt/polymorph) was a way to  
change the properties of a drug relevant to its formulation and use. Court comment:  
this is correct only so far as it goes because it was equally known that no crystal  
might form, and in any event no one knew or could predict any resulting properties.  
F. Skilled persons would, as a matter of routine, prepare a number of different salts  
under various conditions and verify the properties of these salts in parallel, that is,  
conduct a screen. This is among the most routine tasks for those in the industry.  
There is always an expectation that salt selection will lead to crystalline forms. Court  
comment: I disagree: I decline to find salt screens among the most routine tasks.  
Page: 142  
Moreover the test of fair expectation of successwas not approved in Eli Lilly v  
Mylan, 2015 FCA 286 at para 4.  
G. Experts from both parties agreed that virtually all salts will be isolatable as crystals.  
Solubility, permeability, bioavailability, crystallinity and hygroscopicity were  
properties that would have been evaluated as part of the screen. The skilled person  
would expect that one or more salt forms having suitable properties for development  
would be identified. Court comment: I disagree. The Skilled Person would know that  
some salts would not crystallize; ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
|||||||||||||||||||||||| What the Skilled Person would see was a course of experimentation in  
the nature of a research program.  
H. The skilled person would characterize the solid state form by XRPD and DSC as an  
ordinary part of pharmaceutical development. Court comment: I agree. I would note  
that identifying the XRPD is simply one method of characterizing a substance.  
I. The skilled person would always expect that ODV would be useful in the treatment  
of depression irrespective of its salt or polymorphic form. Court comment: I  
disagree; one may say that ODV was known to be useful in the treatment of  
depression; for use in treatment as drug that did not require metabolization in the  
body, ODV would have to be formulated into a drug with solid state stability, and a  
drug was soluble, permeable and bioavailable; no Skilled Person could identify  
which if any salt would qualify let alone which if any crystal would have the  
Page: 143  
appropriate mix of properties for development as a drug, let alone its effective  
therapeutic dosage(s).  
J. ODV was understood to be a basic compound. As such, it was known that ODV  
would be made into a salt by reacting it with an acid. The skilled person would  
screen a group of acids known for their use in creating pharmaceutically-acceptable  
salts. Court comment: I agree, although nothing in the prior art pointed specifically to  
ODV as opposed to other acceptable salts.  
K. The skilled person would know that acids having a pKa of 2-3 units lower than that  
of ODV would form a salt. The skilled person would include succinic acid in his or  
her screen. Court comment: I agree.  
L. Succinic acid was a common acid used to form salts of pharmaceuticals, has a pKa  
within 2-3 units of ODVs, and repeatedly appeared in the lists of possible salts for  
ODV in the prior art. In addition, it was known that the fumarate salt of ODV had  
been prepared and was crystalline. Succinic acid is similar in structure to fumaric  
acid. Court comment: I agree.  
M. Given the similarity in structure, it was expected that succinic acid would also form  
as a crystalline solid. Additionally, succinic acid is more soluble than fumaric acid,  
and it was thus expected that ODV-S would be more soluble than ODV fumarate.  
Court comment: I disagree; these are matters that the Skilled Person knew would  
entail detailed and specific experimentation as part of a research program.  
Page: 144  
N. The solvents and conditions that would yield the succinate salt of ODV, including  
Form I, would be those used routinely. Court comment: the Skilled Person could  
neither identify nor predict Form I ODV succinate.  
O. Typically, the most stable form of crystal would be the one most likely to form in the  
screen, and would be the least likely to undergo a crystal form change in the  
formulation process. Court comment: by definition the most stable form of crystal  
would be the least likely to undergo a change.  
P. The generally accepted practice was to prepare and use the most stablecrystal  
form (polymorph) of a crystalline salt. ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
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Q. No special steps were needed to arrive at Form I. Court comment: I disagree; while  
what became known as Form I ODV succinate was developed by Wyeth using its  
domestic and international facilities, that was preceded by pro-drug experiments and  
work on other salts including the fumarate salt. The fact remains that the salt screen  
work did not have an identified and predictable outcome; ODV succinate the salt had  
never been made before. I do not consider SSCIs specialized polymorph screening  
to be routine work, nor was the overall drug development program including work on  
a prodrug and other unsuccessful salts routine experimentation of the type  
performable by the unimaginative uninventive Skilled Person. Work in this regard  
Page: 145  
was in the nature of a research program especially when the in vitro, in vivo and  
human tests and experimentation are considered as they must be.  
R. Once a useful salt was identified, the skilled person would choose a formulation to  
deliver the medicine in the manner appropriate for treatment. If an instant release of  
the drug was needed, immediate release compositions would be prepared. If a lower  
but sustained release was desired, a sustained release composition would follow. This  
was all routine work in the development of a new drug. ODV salts were identified as  
being particularly suited for inclusion in a sustained release formulation due to  
ODVs relatively long half-life. Prior art (e.g., WO 955, WO 851, EP 374 and US  
186) disclosed the preparation and use of oral dosage forms containing ODV and its  
salts (including ODV-S) for use in the treatment of CNS disorders. Sustained release  
oral dosage forms, including those previously described for use with venlafaxine or  
as conventional sustained release oral formulations were said to be advantageous  
formulations because they would control the blood levels of the drug and therefore  
reduce the occurrence of side effects associated with use of venlafaxine, including in  
particular nausea and headache. Preparing and modifying these formulations to vary  
the drugs pharmacokinetic parameters was routine work for a formulator. Court  
comment: I disagree: the prior art did not disclose either the ODV succinate or Form  
I ODV succinate let alone the sustained release version with the pharmacokinetic  
properties claimed in Claims 43 and 44. Much of this assertion is argumentative and  
contrary to the evidence I have accepted of Dr. Myerson and others and the  
experience of Dr. Park.  
Page: 146  
S. The skilled person would be motivated to prepare ODV-S with the expectation that it  
would form a crystalline salt that would be useful as a medicine. Court comment: I  
disagree; there was no motivation in the prior art to prepare either the succinate salt  
let alone crystalline Form I ODV succinate.  
T. Once formed, the skilled person would determine its solubility, permeability,  
bioavailability, crystallinity, hygroscopicity and stability and would characterize its  
solid state forms by DSC and XRPD. Court comment: I agree; the key is once  
formedwhich was neither predicted nor predictable and in respect of which the  
Skilled Person foresaw a research program.  
U. In so doing, he or she would obtain ODV-S, including Form I ODV-S, would  
measure its XRPD and its endotherm, all without inventive effort. Court comment: I  
disagree because this is the product of several previously rejected premises.  
V. Claims 33 is also obvious. In addition to the above, the Skilled Person knew that  
ODV-S would be useful for the treatment of depression. Neither the salt nor the  
polymorphic form imparts the therapeutic properties of ODV. The Skilled Person  
would know that, when administered, the salt would dissolve and dissociate from the  
ODV, lose its solid form, and be available in the body to treat depression. Court  
comment: I disagree; Claim 33 depends on Claims 8 and 9 and to the extent they are  
not obvious, Claim 33 is not obvious. Claims 8 and 9 were not obvious nor obvious  
to try therefore neither was Claim 33.  
Page: 147  
W. Claims 43 and 44 are also obvious for the same reasons. The Skilled Person also  
knew that the higher the Cmax, the greater the incidence of side effects. It was self-  
evident that a formulation that induces a Cmax of less than 225 ng/ml (e.g., 50  
ng/ml) would have lower side effects than formulations which did not. The Skilled  
Person also knew that the Cmax could be decreased by administering ODV-S in a  
sustained release oral dosage form as discussed above. While the prior art did not  
disclose that an ODV dosage form Cmax ought to be less than 225 ng/ml, this  
information was easily ascertained through the use of commercial software and  
available pharmacokinetic data derived from Effexor XR or pharmacokinetic  
modeling techniques. Court comment: I disagree with this line of argument because  
Claims 43 and 44 depend on Claims 8 and 9; to the extent Claims 8 and 9 were not  
identified or predicted in the prior art and could not be known to the Skilled Person,  
the same must be said of Claims 43 and 44.  
X. In any event, the 225 ng/ml C. value is of no practical significance to the working of  
the claim 43 and 44 formulations because this value was arrived at arbitrarily and in  
an unexplainable manner. Court comment: this submission has no merit as discussed  
at para 110.  
[301] While I have dealt in summary fashion with each of the Apotexs prior art arguments, the  
more fundamental problem with these arguments is that they are contrary to the expert evidence I  
have accepted. That aside, even if all of these arguments are accepted as being in the prior art,  
Page: 148  
contrary to my finding, in my view they set up the much the same situation as was rejected by  
the Supreme Court in Sanofi:  
[85] Just because there are known methods of separating a  
racemate into its isomers does not mean that a person skilled in the  
art would necessarily apply them. The fact that there are such  
known methods of separation will be of no account if the evidence  
does not prove that it was more or less self-evident to try them.  
[302] As Sanofi put it, knowing these procedures existed is of no account because the evidence  
does not prove it was more or less self-evident to try them: a possibility of finding the invention  
is not enough. The invention must be self-evident from the prior art and common general  
knowledge in order to satisfy the obvious to trytest. That is not the evidence in this case.”  
[para 85] As I understand it, knowing a host or multiplicity of different facts and procedures does  
not necessarily lead to the conclusion that it was obvious to try to find everything that could be  
made based on those facts and procedures. This is because, as Sanofi confirms at para 65: [I]f it  
were otherwise there would be few inventions that were patentable. The only research which  
would be worthwhile (because of the prospect of protection) would be into areas totally devoid  
of prospect. The obvious to trytest really only works where it is more-or-less self-evident that  
what is being tested ought to work.”  
[303] That is not the evidence in this case either: the invention was not self-evident from the  
prior art and the common general knowledge and on the evidence in this case. I am unable to  
find that the uninventive and unimaginative Skilled Person would consider the invention or  
Page: 149  
discovery of Form I ODV succinate was self-evident from the prior art and the common general  
knowledge.  
[304] In my view, these considerations under this heading point against a finding of obvious to  
try in this case.  
8.  
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?  
[305] I have accepted the evidence of Dr. Myerson on the extent, nature and amount of effort to  
achieve the invention as known to the Skilled Person paras 234 and 278. I also have accepted  
Dr. Parks experience-based evidence on crystallization and polymorph screening - para 124 and  
following. In my respectful view, the extent nature and amount of effort required to achieve the  
invention, that is, to achieve Form I ODV succinate, was considerable; what was needed would  
be seen by the Skilled Person as a research program.  
[306] Again by analogy to Sanofi at para 86, there is no evidence that at the relevant time a  
Skilled Person would know which salt, or which crystalline form, would work to achieve the  
invention i.e., the crystalline Form I ODV succinate. In fact, in this case the evidence appears  
stronger than that in Sanofi against obviousness to try, because here there is evidence which I  
accept on a balance of probabilities that the salt ODV succinate in fact would not work. This  
evidence was based on the fact that ODV fumarate, another salt of ODV, had not worked.  
Because ODV in its dissociated state, i.e., separated from the ODV fumarate salt once dissolved,  
 
Page: 150  
did not work when introduced into the body, it was logical to expect that a different salt, namely  
ODV succinate, also would not work, because the ODV dissociated from the succinate salt  
would be the same as the ODV dissociated from the fumarate salt. If one did not work it was  
logical the other would now work. I also accept Dr. Shahs evidence of ||||||||||||||||||||||||||||||||||||||||||||||||  
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|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| The nature of the work seen in this context was uphill.  
[307] Also by analogy to Sanofi, at para 87, there was no evidence that at the relevant time the  
Skilled Person would know the properties of ODV succinate, nor would the Skilled Person have  
known or predicted the properties of the novel crystalline form claimed in the 668 Patent.  
[308] While I agree that salt screening may not have been seen by the Skilled Person as  
prolonged and arduous, that is not the case with the crystallization and polymorph screening  
performed by SSCI, which I find would have been seen as difficult and prolonged. In addition,  
the Skilled Person would see as prolonged and arduous the overall research program that was  
conducted here, which in my view was justified and reasonable in this drug development context,  
which included pro-drug experimentation, salt screening and polymorph screening together with  
the in vitro and in vivo testing including that in ||||||||||||||||||||||||, rats, dogs and humans.  
[309] This factor points away from finding obvious to try.  
9.  
Is there a motive provided in the prior art to find the solution the patent addresses?  
 
Page: 151  
[310] What is required to establish motivation is whether there is a motive provided in the prior  
art to find the solution the patent addresses. The solution the 668 Patent addresses as found is  
the new composition of matter namely crystalline Form I ODV succinate.  
[311] There is no evidence of motivation in the prior art that points in the direction of the  
succinate salt of ODV, nor to any particular solid state form of ODV succinate, let alone the  
Form I monohydrate. This is not unexpected given the Skilled Person would have had no  
knowledge or predictability of what forms existed nor how they could be formed.  
[312] Pfizers position is that beyond a general statement about the possibilities of other  
pharmaceutically acceptable salts of ODV, there was no pre-existing motive provided in the prior  
art to find the solution provided by the 668 Patent. It says, and I agree, that while a Skilled  
Person perhaps would have had a general motive to find a form of ODV that could be  
formulated, there was no suggestion as to which salts might have crystalline forms. In my view,  
and in addition, there was no evidence of motivation pointing in the direction of succinate salt as  
the solution and certainly no evidence of motivation to prepare any particular solid state form of  
ODV succinate, let alone Form I ODV succinate which is the solution taught by the 668 Patent.  
[313] Again, I look at Sanofi, this time at para 90, and note that the Supreme Court examined  
the facts for evidence that provided a specific motivation for the skilled person to pursuethe  
invention claimed. That is the same situation here, there is a lack of specific motivation, and I  
Page: 152  
emphasize the words specific motivationin the prior art to find the novel crystalline Form I  
ODV claimed by the 668 Patent.  
[314] I note also that Sanofi dealt with a genus patent, where, as the Supreme Court stated at  
para 90, selection might be expected, but nonetheless Sanofi found no motivation in the prior  
art: neither do I. Apotex accepts this is not a selection patent.  
[315] In my view, this aspect of the obvious to try test favours Pfizer.  
10.  
What is the course of conduct which was followed which culminated in the making of the  
invention?  
[316] The course of conduct in this specific case, that is, the invention story regarding the 668  
Patent is outlined above as deposed by Drs. Shah and Park. Based on my findings in that regard,  
I am unable to conclude that the course of conduct that was followed and which culminated in  
the crystalline Form I ODV succinate was routine.  
[317] I agree with Apotex that the salt form ODV succinate was made as a new composition of  
matter ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||| However, and without doubting its relevance, the time taken to make a  
new invention is only one factor. This is particularly the case given the evidence that this  
particular salt and crystalline form was not predicted or predictable. I have noted the evidence,  
 
Page: 153  
and already found that salt forms in fact were seen as counter-intuitive ||||||||||||||||||||||||||||||||||||||  
|||||||||||||||||||||||| based on the fact that the salt form ODV fumarate had not worked.  
[318] ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
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||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
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[319] Moreover, the invention story did not start at the salt screen or the identification of the  
succinate salt as a possible candidate for further testing and drug development. To start the  
analysis there is to ignore the work done before the most recent salt experimentation began,  
including work on other salts including the fumarate salt, and the work directed towards  
developing a pro-drug - which pro-drug work the parties agree took place. It is also to ignore the  
very considerable work in terms of the in vitro and in vivo and human testing that Wyeth  
performed after the detailed and salt screening and specialized crystal polymorph screening. And  
one may not ignore the very considerable work in terms of the in vitro and in vivo and human  
testing that Wyeth performed after the detailed and salt screening and specialized crystal  
polymorph screening.  
[320] ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
Page: 154  
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| But that was neither  
predictable nor predicted. Again, it is but one factor. More importantly, the major purpose of  
SSCIs involvement was that extensive additional testing was necessary to determine whether  
there were other forms of ODV succinate, and if so which form of ODV succinate was the most  
stable, i.e., the best candidate for further drug development. The fact that the new crystalline  
composition of matter was made before Wyeth engaged SSCI does not detract from the facts that  
a) the experimentation required to get to that point was more than routine in this case and b) that  
further experimentation was required from the specialists at SSCI.  
[321] On balance, and in my respectful view, the actual course of conduct in this case entailed  
more than routine experimentation; in my view it was a research program. This confirms my  
earlier finding that the Skilled Person looking at the prior art and common general knowledge  
would see a research program in terms of finding a compound suitable for drug development that  
had the necessary properties including solid state stability at ambient temperatures and relative  
humidity, solubility, permeability and bioavailability.  
[322] That said, while I agree that some of the work done by Wyeth and SSCI was not arduous,  
viewed overall it was nonetheless difficult. In my view, in this connection, the comments of  
Gauthier JA in Plavix 2 are appropriate:  
137  
However, Rothstein J. made it clear in Plavix that whether  
the separation or resolution of the enantiomers was routine or  
involved arduous work would assume small significance in this  
case when one considers the whole course of conduct that led to  
the decision to separate (See Plavix at para 89).  
Page: 155  
[323] These circumstances favour Pfizer in the obvious to try analysis.  
11.  
Conclusion on obvious to try regarding Claims 8 and 9  
[324] In summary, based on the above, I find on a balance of probabilities that it was not more  
or less self-evident to the Skilled Person that what is being tried, i.e., the inventive concept or  
solution taught by the 668 Patent namely the crystal Form I ODV succinate as claimed in Claims  
8 and 9, ought to work.  
12.  
Conclusion on obvious to try regarding Claims 33, 43 and 44  
[325] Because Claims 33, 43 and 44 depend on Claims 8 and 9, I conclude that their respective  
inventive concepts, the solutions they teach, were also not obvious to try.  
13.  
Consideration of the guidance for obvious to try analysis set out in Sanofi  
[326] I have made these findings without specific reference to the guidance set out at the start  
of the obvious to try outline in Plavix 1. There, the Court stated that the obvious to try doctrine  
must be approached cautiouslyand is only one factor to assist in the obviousness inquiry,  
not a panaceaat para 64.  
[327] That need to be cautious in approach leads me to the same conclusion as just made, as  
does being guided by the clear warning that obvious to try is not a panacea.  
     
Page: 156  
[328] I turn to the Supreme Courts considerations in Sanofi respecting the purposes of the  
Patent Act, namely that: [T]he patent system is intended to provide an economic encouragement  
for research and development. It is well known that this is particularly important in the field of  
pharmaceuticals and biotechnology.[at para 64] This guidance confirms my finding on a  
balance of probabilities that Apotexs allegation of obvious to try is not established.  
[329] In summary, the guidance provided by the Supreme Court with respect to obvious to try  
supports the conclusions that Form I ODV succinate was not obvious to try.  
14.  
Conclusion on obviousness  
[330] In my respectful view, the Applicant has established on a balance of convenience that  
Apotexs allegation of obviousness is not justified.  
5.  
Inutility  
[331] The statutory basis for the proposition that a patent is invalid for inutility, or put another  
way, that it lacks utility, is set out in the Patent Act at s 2 where it is enacted that an invention  
must be useful:  
invention means any new and  
invention Toute réalisation,  
useful art, process, machine,  
tout procédé, toute machine,  
manufacture or composition of fabrication ou composition de  
matter, or any new and useful  
improvement in any art,  
matières, ainsi que tout  
perfectionnement de lun  
process, machine, manufacture deux, présentant le caractère  
or composition of matter;  
de la nouveauté et de lutilité.  
(invention)  
(invention)  
   
Page: 157  
[Emphasis added.]  
[Soulignement ajouté.]  
[332] Previously, the discussion of utility would have started out by identifying the need for  
utility to be either demonstrated or soundly predicted, and then discuss the Promise Doctrine.  
However, subsequent to the hearing in this matter, the Supreme Court of Canada held that the  
application of the Promise Doctrine is not the correct approach to determine whether a patent has  
sufficient utility.See AstraZeneca v Apotex, 2017 SCC 36 [AstroZeneca] at para 2. I invited  
submissions from the parties concerning AstraZeneca originally requesting revised submissions  
on utility. Apotex asked that it be allowed to file submissions on anticipation and obviousness in  
addition to utility, and as a consequence I asked the parties to file submissions concerningthe  
AstraZeneca decision and the case at bar. Both parties filed main and responding submissions.  
[333] Pfizer summarized its arguments on utility this way:  
1.  
In AstraZeneca Canada Inc. v. Apotex Inc.  
(AstraZeneca), the Supreme Court significantly modified the law  
of utility by expressly overturning the Promise Doctrine,which  
it found to be unsound,” “excessively onerous,and counter to  
the scheme of the [Patent Act].Instead, the Court introduced a  
new two-step utility approach. First, courts must identify the  
subject matter of the invention as claimed in the patent. Second,  
courts must consider whether that subject matter is useful. A  
scintilla of utility will do,and a single use is sufficient to satisfy  
the utility requirement under section 2 of the Patent Act (the  
Act), even if multiple uses are disclosed or described.  
2.  
Even under the now-rejected promiseapproach, the  
Asserted Claims of the 668 Patent had sufficient utility. Therefore,  
under the new framework, with its substantially lower threshold,  
Apotexs allegations of inutility cannot be justified. While the 668  
Patent may disclose multiple uses relating to various aspects of its  
subject matter, the subject matter of claims 8 and 9 is the novel  
crystal form Form I ODV succinate. Applying the Supreme  
Page: 158  
Courts guidance, the utility associated with that novel crystal form  
is solid-state stability, which the inventors demonstrated prior to  
the relevant date. This is a complete answer to Apotexs allegation  
that the subject matter of claims 8 and 9 lack utility under section 2  
of the Act.  
3.  
Apotex cannot reasonably maintain its position that these  
claims lack utility in light of the decision in AstraZeneca. It has not  
contested that the stability of Form I ODV succinate was  
demonstrated. Rather, Apotexs argument that claims 8 and 9 lack  
utility was based on its allegation that these claims were associated  
with a number of promises, including promises relating to  
comparative properties of the salt, and the reduction of side-  
effects. Now that it is clear that any utility is sufficient to support a  
claim, Apotexs allegation cannot succeed.  
4.  
In AstraZeneca, the Court reminded parties that patents are  
designed to provide inventive solutions to practical problems. That  
is precisely what the 668 Patent does. The inventors had a  
problem: prior forms of ODV exhibited unfavourable properties  
for drug development. They conducted experiments to try to solve,  
and ultimately succeeded in solving, that problem. Through those  
experiments, they discovered a new salt (ODV succinate) with  
improved properties and a novel crystal form (Form I ODV  
succinate) that was sufficiently stable for development. Based on  
AstraZeneca, the stability of Form I, and therefore its suitability for  
pharmaceutical development, is sufficient utility to support claims  
8 and 9, regardless of what other uses the patent specification may  
disclose.  
5.  
Finally, the only issue before the Supreme Court in  
AstraZeneca was the utility required under section 2 of the Act.  
The Court did not address the law of either obviousness or  
anticipation and nothing in the AstraZeneca decision alters the  
tests for obviousness or anticipation it previously set out in Sanofi-  
Synthelabo.  
[334] Apotex summarized its utility arguments (it also raised obviousness and overpromising  
but did not revisit anticipation) as follows:  
15.  
In AstraZeneca, the Supreme Court held that the promise  
of the patentdoctrine as described by the Court is not the correct  
Page: 159  
approach to determine whether a patent claim has the utility  
required. At the same time, the Supreme Court reaffirmed the  
utility requirement in unequivocal terms and directed that utility be  
determined as follows:  
(a)  
First, the court must identify the subject  
matter of the invention as claimed in the patent;  
(b)  
Second, the court asks whether the subject  
matter is useful. In this regard, usefuldoes not  
mean that any use will do- it means that the  
subject matter works as a solution to a practical  
problem, is capable of an actual relevant  
use...related to the nature of the subject-matter, and  
carries out some useful objective and is not merely  
a laboratory curiosity whose only possible claim to  
utility is as a starting material for further research.”  
16.  
The Supreme Court also reaffirmed that the utility as  
construed must be established by either demonstration or sound  
prediction as of the filing date of the patent.  
[335] In this connection the Supreme Court in AstraZeneca itself sets out the correct approach  
to utility:  
(2) The Correct Approach to Utility  
[52] The words in s. 2 of the Act ground the type of utility that  
is pertinent by requiring that it is the subject-matter of an invention  
or improvement thereof that must be useful. For the subject-matter  
to function as an inventive solution to a practical problem, the  
invention must be capable of an actual relevant use and not be  
devoid of utility. As stated by Justice Binnie in AZT, a patent is a  
method by which inventive solutions to practical problems are  
coaxed into the public domain by the promise of a limited  
monopoly for a limited time(para 37, (emphasis added)).  
[53] Utility will differ based on the subject-matter of the  
invention as identified by claims construction. Thus, the scope of  
potentially acceptable uses to meet the s.2 requirement is limited –  
not any use will do. By requiring the usefulness of the proposed  
invention to be related to the nature of the subject-matter, a  
Page: 160  
proposed invention cannot be saved by an entirely unrelated use. It  
is not sufficient for a patentee seeking a patent for a machine to  
assert it is useful as a paperweight.  
[54] To determine whether a patent discloses an invention with  
sufficient utility under s.2, courts should undertake the following  
analysis. First, courts must identify the subject-matter of the  
invention as claimed in the patent. Second, courts must ask  
whether that subject-matter is useful - is it capable of a practical  
purpose (i.e. an actual result)?  
[55] The Act does not prescribe the degree or quantum of  
usefulness required, or that every potential use be realized a  
scintilla of utility will do. A single use related to the nature of the  
subject-matter is sufficient, and the utility must be established by  
either demonstration or sound prediction as of the filing date (AZT,  
at para 56).  
[336] The first question is to identify the subject-matter of the invention as claimed in the  
patent. The second question the Court must ask is whether that subject-matter is useful - is it  
capable of a practical purpose (i.e. an actual result). The utility must be either demonstrated or  
soundly predicted.  
[337] AstraZeneca states that utility will differ based on the subject-matter of the invention as  
identified by claims constructionat para 53. Utility is assessed on a claim by claim basis after  
AstraZeneca as it was before AstraZeneca: AstraZeneca v. Apotex, 2015 FCA 158, paras 4 and 5,  
and Apotex v Pfizer, 2014 FCA 250, in accordance with s 58 of the Patent Act and para 46 of  
AstraZeneca itself.  
Page: 161  
[338] Therefore the Courts utility analysis will proceed on a claim by claim basis, having  
regard to the construction given each of the asserted claims in the 668 Patent, namely Claims 8,  
9, 33, 43 and 44.  
[339] Claims 8 and 9 - I have found that subject matter of Claims 8 and 9 are to the novel  
crystalline Form I ODV succinate as characterized by its XRPD and endotherm. These claims to  
the Form I crystal form in my view cover distinct subject matter over the claims of the 668  
Patent directed more generally to the novel salt ODV succinate, as the 668 Patent confirms,  
[E]ach polymorph forms another aspect of the invention.In this regard, Apotexs Dr. Parr  
agreed this statement in the 668 Patent means an aspect of the invention in addition to the  
invention of the novel salt.”  
[340] Pfizer says that the usefulness, the utility, of Claims and 9 is its usefulness as a stable,  
solid state form of ODV succinate. I agree. I also agree that this use is directly related to the  
subject matter of Claims 8 and 9. Stability (i.e., the tendency not to change to other forms) is an  
important property for a new crystal form and there is ample evidence that stability was required  
for this pharmaceutical development.  
[341] Apotex disagrees saying that stability is one of the physical properties of the drug (e.g.,  
mass, colour, melting point, stability, etc.), and that utility it is what the drug can do as a  
practical matter (i.e, treat disease) and not its properties. I disagree: in my respectful view a drug  
that is not stable across the manufacturing, distribution and storage processes cannot readily be  
Page: 162  
seen as useful, rather in my view the reverse. I am not persuaded by Apotexs arguments on this  
point particularly because it is the solid state stability of Form I that makes it possible to use  
Form I ODV succinate in formulation i.e., as a drug. Both Apotexs Drs. Bastin and Parr agreed  
stability would be important and a factor. Moreover, Apotexs NOA stated that studies would  
need to be conducted to confirm that the solid form of the drug was a sufficiently stable for use  
in a drug product.The search for a stable form of ODV succinate was a very important  
motivator lying behind the work done in regard to Wyeths salt screening, and the polymorph  
and crystal research undertaken by the specialists at SSC1. While Apotex argues that the stability  
Pfizer asserts is only the stability of ODV-S Form I (ground), Pfizer correctly observes that this  
argument is of no moment for the purposes of the AstraZeneca utility analysis because even if  
the claim were limited to groundForm I, which I have held is not the case, it was still shown to  
be useful.  
[342] I am satisfied that the solid state stability of Form I ODV succinate, the subject matter of  
Claims 8 and 9, is subject-matter that is useful - is it capable of a practical purpose (i.e. an actual  
result): it makes it possible to use Form I ODV succinate in formulation i.e., as a drug.  
[343] In my respectful view, the stability of Form I was demonstrated. Form I was shown to be  
stable at room temperature and up to 105ºC, and physically stable from 5% to 95% relative  
humidity. ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
|||||||||||||| This was the evidence of Dr. Park from her work at SSCI which I accepted at paras 131,  
133 and 140 above. Apotexs expert, Dr. Parr admitted that physical stability was demonstrated  
Page: 163  
for Form I (ground) ODV succinate.Indeed, Dr. Parr deposed: If the property of physical  
stability (i.e., physically stable up to 105 °C and from 5-95% relative humidity) forms part of the  
promised utility associated with claims 8 and 9, I agree with Drs. Myerson (at his paras 306 to  
308) and Atwood (at his paras 269 to 271) that this property was demonstrated for Form I  
(ground) ODY succinate.Given my finding re stability, the parties agree on demonstration in  
this respect.  
[344] Pfizer also argued that the practical usefulness of the drug as a stable solid form is alone  
sufficient utility under AstraZeneca in this context, and I agree.  
[345] Therefore Claims 8 and 9 have demonstrated utility.  
[346] Claims 33, 43 and 44 - The other asserted Claims relate to additional subject matter  
disclosed by the 668 Patent. Specifically, and as I found as a matter of claims construction, and  
as it depends on Claims 8 or 9, Claim 33 relates to the use of Form I ODV succinate in the  
treatment of depression.  
[347] Claim 43, as it depends on Claims 8 or 9, as I have found as a matter of claims  
construction, relates to the use of a sustained release formulation of Form I ODV succinate to  
induce a particular blood plasma concentration and reduce the incidence of side effects that occur  
with a non-sustained release formulation. Claim 44 relates to the same sustained release  
formulation containing ODV succinate in any form.  
Page: 164  
[348] These claims cover further uses of the subject matter of Claims 8 and 9, which brings us  
the next question per AstraZeneca: whether that subject-matter is useful - is it capable of a  
practical purpose (i.e. an actual result).  
A.  
Are the subject matters of Claims 33, 43 and 44 useful - are they capable of a practical  
purpose (i.e. an actual result)?  
[349] Claim 33 - In my respectful view, the inventors had both demonstrated and soundly  
predicted that Form I ODV succinate was capable of a practical purpose (i.e. an actual result)  
namely, that it could be used in the treatment of depression. ODV itself was already known in  
the art to be useful for the treatment of depression, so long as it could be effectively  
administered. The Skilled Person would know that if any particular form of ODV succinate  
could be effectively administered into a patients bloodstream, it would similarly be useful for  
this purpose because ODV would have dissociated. The inventors of the 668 Patent had  
demonstrated by the filing date that Form I ODV succinate could be administered so as to result  
in effective blood concentrations of ODV in human patients. Thus, utility associated with Claim  
33 was demonstrated.  
[350] In my view Form I ODV succinate utility to treat depression was also soundly predicted  
based on the known pharmacology of ODV and the fact that Form I ODV succinate had been  
shown to be capable of getting into the bloodstream. It was known that ODV was  
pharmacologically active as a SNRI and it was known that ODV was the active metabolite of  
venlafaxine, which was approved and used for the treatment of depression as EFFEXOR and  
 
Page: 165  
EFFEXOR XR. In other words, the anti-depression pharmacological activity of ODV was  
known. Further, as just noted Form I ODV succinate was shown to be capable of getting into the  
bloodstream at therapeutically effective concentrations.  
[351] In my view, the conclusion that Form I ODV succinate could get into the bloodstream  
where it would be expected to be useful for all of the clinical uses for which ODV was already  
known to be useful including usefulness to treat depression was therefore based on a sound line  
of reasoning.  
[352] Claims 43 and 44 - In my view the inventors demonstrated at the relevant time that  
sustained release formulations of ODV succinate (specifically, Form I ODV succinate) that  
induced the requisite blood plasma level led to an overall reduction in side effects as compared  
with immediate release formulations.  
[353] In my view this use is a practical result related to the subject matter of Claims 43 and 44,  
which cover sustained release formulations. These formulations are intended to release a drug  
more slowly in order to reduce blood concentrations and therefore side effects.  
B. Conclusion on inutility  
[354] I am satisfied on a balance of probabilities that Apotexs allegations of inutility are not  
justified.  
 
Page: 166  
6.  
Overpromising in relation to subsection 27(3) of the Patent Act  
[355] In its post-hearing submissions directed to the Supreme Court of Canadas decision in  
AstraZeneca, Apotex quite expectedly made submissions on the issue of utility. I say expectedly  
because AstraZeneca changed the law in Canada on the Promise Doctrine in the utility analysis.  
As noted previously, Apotex also made submissions to the effect that AstraZeneca altered the  
law of obviousness, a proposition I did not accept. In addition, Apotex submitted that the 668  
Patent overpromisesin violation of the requirements of subsection 27(3) of the Patent Act,  
such that the Patent is invalid.  
[356] To this end, Apotex argued:  
31.  
Apotexs alleged and provided evidence to establish that  
the 668 Patent overpromised. In particular, Apotex alleged that the  
668 patent promised (1) high and improved solubility,  
permeability, and bioavailability when compared with ODV free  
base and ODV fumarate; (2) the oral administration of ODV-S  
results in a lower incidence of side effects compared to the  
administration of venlafaxine, ODV free base and salts of ODV  
other than ODV-S; and (3) when ODV-S is administered from a  
sustained release oral dosage form, it results in a lower incidence  
of side effects relative to the oral administration of venlafaxine,  
ODV free base, and salts of ODV other than sustained release  
formulations of ODV-S. Apotex established that these promises  
were not demonstrated or soundly predicted as of the filing date of  
the 668 patent.  
32.  
Pfizer did not dispute that these promises were made, but  
rather asserted that not all of these promises ought to constitute the  
utility of each of the claims. For example, Pfizers position was  
that the promises of improvements in side effects ((2) and (3)  
above) ought be read to inform the utility of claims other than  
claims 8, 9 and 33.  
 
Page: 167  
33.  
As noted above, in AstraZeneca, the Supreme Court  
directed that overpromising violates the requires of subsection  
27(3) of the Patent Act. An invention is subject matter that has  
demonstrated utility as of the filing date, or subject that matter that  
constitutes a sound prediction as of the filing date. The statements  
in the 668 patent to the effect that the compounds of the patent  
have the utilities (1)-(3) above were thus not correct and full’  
descriptions of the invention but rather were overpromises. As  
such, they ought to invalidate the 668 patent as a whole.  
[357] I agree that the Supreme Court of Canada in AstraZeneca declared overpromising to be a  
a mischief. However, instead of addressing overpromising within the law of utility, as the  
Promise Doctrine had done, the Supreme Court directed at para 46 that the scheme of the  
[Patent] Act treats the overpromising in multiple ways, including reference to subsection 27(3)  
of the Patent Act. Subsection 27(3) provides:  
Specification  
Mémoire descriptive  
(3) The specification of an  
invention must  
Le mémoire descriptif doit :  
(a) correctly and fully describe a) décrire dune façon exacte  
the invention and its operation et complète linvention et son  
or use as contemplated by the  
inventor;  
application ou exploitation,  
telles que les a conçues son  
inventeur;  
(b) set out clearly the various  
steps in a process, or the  
method of constructing,  
b) exposer clairement les  
diverses phases dun procédé,  
ou le mode de construction, de  
making, compounding or using confection, de composition ou  
a machine, manufacture or dutilisation dune machine,  
composition of matter, in such dun objet manufacturé ou  
full, clear, concise and exact  
terms as to enable any person  
skilled in the art or science to  
which it pertains, or with  
which it is most closely  
dun composé de matières,  
dans des termes complets,  
clairs, concis et exacts qui  
permettent à toute personne  
versée dans lart ou la science  
connected, to make, construct, dont relève linvention, ou  
compound or use it;  
dans lart ou la science qui sen  
rapproche le plus, de  
Page: 168  
confectionner, construire,  
composer ou utiliser  
linvention;  
(c) in the case of a machine,  
explain the principle of the  
machine and the best mode in  
which the inventor has  
contemplated the application  
of that principle; and  
c) sil sagit dune machine, en  
expliquer clairement le  
principe et la meilleure  
manière dont son inventeur en  
a conçu lapplication;  
(d) in the case of a process,  
explain the necessary  
d) sil sagit dun procédé,  
expliquer la suite nécessaire, le  
sequence, if any, of the various cas échéant, des diverses  
steps, so as to distinguish the  
invention from other  
inventions.  
phases du procédé, de façon à  
distinguer linvention en cause  
dautres inventions.  
[358] Apotex raises an entirely new argument in this connection. It made no reference to  
overpromising in its memorandum of fact and law. Nor did it refer to overpromising in any of the  
outlines of argument filed at the hearing. Nor was overpromising discussed by Apotex at the  
hearing. And while Apotex did refer to subsection 27(3) of the Patent Act in its memorandum, it  
made but a single reference and that was in connection with insufficiency and overbreadth;  
Apotex subsequently withdrew both those arguments.  
[359] While I do not fault Apotex for raising its overpromisedoctrine given the invitation to  
make additional comments on AstraZeneca, I note Apotex did not ask to raise overpromising”  
in its letter of July 4, 2017, in which it requested a broadening of the scope of post hearing  
submissions: it only asked to raise anticipation and obviousness. Thus, while Apotex raised  
obviousness in its post-hearing filings, it said nothing about anticipation; instead it raised the  
new issue of overpromising.  
Page: 169  
[360] I also observe that the alleged overpromises resemble the promise arguments advanced  
by Apotex, which are no longer valid having regard to AstraZeneca. If the Supreme Court  
intended to say, in effect, that the Promise Doctrine was not good law in terms of utility under  
s 2, but was good law in terms of patent specifications under subsection 27(3) it could have done  
so; it did not.  
[361] Pfizer opposes Apotexs submissions on overpromising. It puts its argument this way:  
4.  
Apotexs position in both this case and in AstraZeneca was  
that s. 2 of the Act requires a patentee to demonstrate or predict  
every plausible benefit mentioned in the patents specification. The  
Supreme Court described that position and the Promise Doctrine as  
unsound,” “excessively onerous,” “incongruent with … the  
scheme of the [Act]and not good law.Undeterred by this strong  
language, Apotex now suggests that this requirement was correct  
all along and should still be applied, and that what the Supreme  
Court corrected was the relevant section of the Act (s. 27(3) instead  
of s. 2). This Court should not accept Apotexs opportunistic  
invitation to rewrite long-established disclosure principles and  
the Act itself on the basis of an obiter comment of the Supreme  
Court.  
5.  
The Supreme Court did not direct that overpromising  
violates the require[ments] of subsection 27(3).Read purposively,  
the Court was referring to those extraordinary circumstances in  
which the statements in a patent prevent a skilled reader from  
understanding the nature of the inventionor how it is put into  
operation.These have always been (and remain) the core  
requirements of s. 27(3), as the Supreme Court has recently re-  
affirmed in Teva v. Pfizer.  
6.  
Section 27(3) represents the patent bargain. It exists to  
ensure that when the period of monopoly has expired the public  
will be able … to make the same successful use of the invention as  
the inventor could at the time of his application.The promise  
doctrine was eliminated, among other reasons, because it  
discourages rather than encourages disclosure. As the Supreme  
Court said, [t]o invalidate a patent solely on the basis of an  
Page: 170  
unintentional overstatement of even a single use will discourage a  
patentee from disclosing fully, whereas such disclosure is to the  
advantage of the public.”  
[362] The Supreme Court in AstraZeneca stated:  
[45] Supporters of the doctrine assert that the consequences of  
the Promise Doctrine play a key role in ensuring patentees do not  
overpromisein their patent applications. That is, a patentee will  
be dissuaded from stating the invention can be used for things that  
are not sufficiently established at the time of filing if doing so  
would risk invalidating the entire patent. The utility requirement  
should not be interpreted, however, as the Federal Courts have  
done, to address such concerns. Nonetheless, overpromising is a  
mischief.  
[46] The scheme of the Act treats the mischief of overpromising  
in multiple ways. There are consequences for failing to properly  
disclose an invention by claiming, for instance, that you have  
invented more than you have. A disclosure which is not correct and  
full, or states an unsubstantiated use or operation of the invention,  
may be found to fail to fulfill the requirements of s. 27(3). An  
overly broad claim may be declared invalid; however, under the  
operation of s. 58 of the Patent Act, remaining valid claims can be  
given effect. As well, this mischief may result in a patent being  
void under s. 53 of the Act, where overpromising in a specification  
amounts to an omission or addition that is willfully made for the  
purpose of misleading.  
[363] It seems to me that Pfizer is correct. I am unable to see a rationale for the argument that  
the Supreme Court of Canada removed the Promise Doctrine from the utility analysis yet  
simultaneously required it to be considered, in the manner Apotex proposes, in the specification  
analysis. If that was the case, a major underlying problem identified by the Supreme Court itself  
would remain, namely that a patentee will be dissuaded from stating the invention can be used  
Page: 171  
for things that are not sufficiently established at the time of filing if doing so would risk  
invalidating the entire patent.See AstraZeneca para 45.  
[364] Not only would this underlying problem persist, but I do not see anything in AstraZeneca  
to the effect that the Supreme Court intended to overrule itself on the focus of subsection 27(3)s  
disclosure requirements, which the Supreme Court itself had recently outlined in Teva Canada  
Ltd v Pfizer Canada Inc, [2012] 3 SCR 625 [Teva]:  
[49] In Consolboard, this Court reviewed the Acts disclosure  
requirements, which at that time were found in s.36. Although  
there are variations in wording between that section and the current  
s. 27(3), the substance of the disclosure requirements has remained  
the same.  
[50] Dickson J. discussed what the specification must contain in  
order to meet the disclosure requirements. He stated clearly that  
the nature of the invention must be disclosed and that the entire  
specification, including the claims, must be considered in  
determining the nature of the invention and whether disclosure was  
sufficient:  
In essence, what is called for in the specification  
(which includes both the disclosure, i.e. the  
descriptive portion of the patent application, and the  
claims) is a description of the invention and the  
method of producing or constructing it, coupled  
with a claim or claims which state those novel  
features in which the applicant wants an exclusive  
right. The specifications must define the precise and  
exact extent of the exclusive property and privilege  
claimed.  
Section 36(1) seeks an answer to the questions:  
What is your invention? How does it work?With  
respect to each question the description must be  
correct and full in order that, as Thorson P. said in  
Minerals Separation North American Corporation  
v. Noranda Mines, Limited [[1947] Ex. C.R. 306]:  
Page: 172  
… when the period of monopoly has expired  
the public will be able, having only the  
specification, to make the same successful  
use of the invention as the inventor could at  
the time of his application. [at p. 316]  
We must look to the whole of the disclosure and the  
claims to ascertain the nature of the invention and  
methods of its performance, … being neither  
benevolent nor harsh, but rather seeking a  
construction which is reasonable and fair to both  
patentee and public. There is no occasion for being  
too astute or technical in the matter of objections to  
either title or specification for, as Duff C.J.C. said,  
giving the judgment of the Court in Western  
Electric Company, Incorporated, and Northern  
Electric Company v. Baldwin International Radio of  
Canada [[1934] S.C.R. 570], at p. 574, where the  
language of the specification, upon a reasonable  
view of it, can be so read as to afford the inventor  
protection for that which he has actually in good  
faith invented, the court, as a rule, will endeavour to  
give effect to that construction. Sir George Jessel  
spoke to like effect at a much earlier date in Hinks  
& Son v. Safety Lighting Company [(1876), 4 Ch.  
D. 607]. He said the patent should be approached  
with a judicial anxiety to support a really useful  
invention.  
In my view it is a well established principle that a  
patent specification is addressed, not to the public  
generally, but to persons skilled in the particular art.  
I am further of the opinion that s. 36(1) does not  
impose upon a patentee the obligation of  
establishing the utility of the invention. [Emphasis  
added; citation omitted; pp. 520-21.]  
Since Consolboard, the Court has constantly applied the principles  
stated by Dickson J., which is a testament to the soundness of his  
reasoning: see, e.g., Monsanto Canada Inc. v. Schmeiser, 2004  
SCC 34, [2004] 1 S.C.R. 902, at para. 18; Whirlpool Corp. v.  
Camco Inc., 2000 SCC 67, [2000] 2 S.C.R. 1067, at para. 52;  
Page: 173  
Pioneer Hi-Bred Ltd. v. Canada (Commissioner of Patents), [1989]  
1 S.C.R. 1623 (Pioneer Hi-Bred), at p. 1636.  
[51] In Pioneer Hi-Bred, the Court referred to Consolboard in  
discussing the Acts disclosure requirements once again. Lamer J.  
(as he then was), writing for the Court, described those  
requirements as follows:  
In summary, the Patent Act requires that the  
applicant file a specification including disclosure  
and claims (Consolboard Inc., supra, at p. 520).  
Canadian courts have stated in a number of cases  
the test to be applied in determining whether  
disclosure is complete. The applicant must disclose  
everything that is essential for the invention to  
function properly. To be complete, it must meet two  
conditions: it must describe the invention and define  
the way it is produced or built …. The applicant  
must define the nature of the invention and describe  
how it is put into operation. A failure to meet the  
first condition would invalidate the application for  
ambiguity, while a failure to meet the second  
invalidates it for insufficiency. The description must  
be such as to enable a person skilled in the art or the  
field of the invention to produce it using only the  
instructions contained in the disclosure . . . and once  
the monopoly period is over, to use the invention as  
successfully as the inventor could at the time of his  
application (Minerals Separation, supra, at p. 316).  
[Emphasis added; citations omitted; pp. 1637-38.]  
[52] In Consolboard and in Pioneer Hi-Bred, the Court  
correctly analysed the disclosure requirements set out in s. 27(3) of  
the Act. The reasoning in those cases should be reaffirmed and  
applied in the case at bar.  
[Emphasis in original.]  
[365] I see nothing in AstraZeneca that alters what I take from the foregoing namely that the  
specifications analysis under subsection 27(3) requires the patentee to define the precise and  
exact extent of the exclusive property and privilege claimed. In addition, nothing in AstraZeneca  
Page: 174  
departs from the proposition that under subsection 27(3), the applicant must disclose everything  
that is essential for the invention to function properly. To be complete, it must meet two  
conditions: it must describe the invention and define the way it is produced or built …. The  
applicant must define the nature of the invention and describe how it is put into operation. A  
failure to meet the first condition would invalidate the application for ambiguity, while a failure  
to meet the second invalidates it for insufficiency.See Teva at para 51 citing to Pioneer Hi-  
Bred Ltd v Canada (Commissioner of Patents), [1989] 1 SCR 1623, pp. 1637-38.  
[366] In the circumstances I do not agree with Apotexs allegations on overpromising, and  
therefore find on a balance of probabilities that they are not justified.  
7.  
Anticipation  
[367] Apotex points to the following summary of the law of anticipation set out in Gilead  
Sciences Inc v Canada (Health), 2016 FC 857:  
[71] The definition of inventionin section 2 of  
the Patent Act requires that it be new, which  
engages the law of anticipation referred to in s. 28.2  
of the Patent Act each of which are set out below:  
2 In this Act, except as  
otherwise provided,  
2 Sauf disposition contraire,  
les définitions qui suivent  
sappliquent à la présente loi.  
(…)  
(…)  
invention means any new and  
useful art, process, machine,  
invention Toute réalisation,  
tout procédé, toute machine,  
manufacture or composition of fabrication ou composition de  
matter, or any new and useful  
improvement in any art,  
matières, ainsi que tout  
perfectionnement de lun  
process, machine, manufacture deux, présentant le caractère  
 
Page: 175  
or composition of matter;  
(invention)  
de la nouveauté et de lutilité.  
(invention)  
28.2 (1) The subject-matter  
defined by a claim in an  
application for a patent in  
Canada (the pending  
application) must not have  
been disclosed  
28.2 (1) Lobjet que définit la  
revendication dune demande  
de brevet ne doit pas :  
(a) more than one year before  
a) plus dun an avant la date de  
the filing date by the applicant, dépôt de celle-ci, avoir fait, de  
or by a person who obtained  
knowledge, directly or  
indirectly, from the applicant,  
in such a manner that the  
subject-matter became  
la part du demandeur ou dun  
tiers ayant obtenu de lui  
linformation à cet égard de  
façon directe ou autrement,  
lobjet dune communication  
qui la rendu accessible au  
public au Canada ou ailleurs;  
(…)  
available to the public in  
Canada or elsewhere; (…)  
[Emphasis added.]  
[Soulignement ajouté.]  
[72] The Supreme Court of Canada in Apotex Inc v Sanofi  
Synthelabo Canada Inc, 2008 SCC 61 at paras 18-37 [Sanofi] held  
that anticipation consists in one publicly available document  
disclosing the content of the patent at issue, such that the patent  
would infringe the prior disclosure when made, and secondly, that  
the prior disclosure must enable the Skilled Person to make the  
invention as claimed:  
[20] In his reasons after referring to s. 27(1) of  
the Act, the applications judge defined anticipation  
as meaning that the exact invention had already  
been made and publicly disclosed(para. 55). Shore  
J. cited this Courts decision in Free World Trust v.  
Electro Sante Inc., [2000] 2 S.C.R. 1024, 2000 SCC  
66, at para. 26, which approved of the test for  
anticipation described in Beloit Canada Ltd. v.  
Valmet OY (1986), 8 C.P.R. (3d) 289 (F.C.A.), at  
p. 297:  
One must, in effect, be able to look at a  
prior, single publication and find in it all the  
information which, for practical purposes, is  
needed to produce the claimed invention  
without the exercise of any inventive skill.  
The prior publication must contain so clear  
Page: 176  
a direction that a skilled person reading and  
following it would in every case and without  
possibility of error be led to the claimed  
invention. [Emphasis added by the  
applications judge.]  
[21] The applications judge noted that the  
English Court of Appeal stated in General Tire &  
Rubber Co. v. Firestone Tyre & Rubber Co., [1972]  
R.P.C. 457, at p. 486:  
If, on the other hand, the prior publication  
contains a direction which is capable of  
being carried out in a manner which would  
infringe the patentees claim, but would be at  
least as likely to be carried out in a way  
which would not do so, the patentees claim  
will not have been anticipated, although it  
may fail on the ground of obviousness. To  
anticipate the patentees claim the prior  
publication must contain clear and  
unmistakable directions to do what the  
patentee claims to have invented [Emphasis  
added by the applications judge.]  
He then noted that in Free World, at para. 26, this  
Court approved the following statement from  
General Tire:  
A signpost, however clear, upon the road to  
the patentees invention will not suffice. The  
prior inventor must be clearly shown to have  
planted his flag at the precise destination  
before the patentee. [p. 486]  
[22] The law of anticipation as explained in  
Beloit and General Tire has been accepted in  
Canada without reservation: see Free World, at  
para. 26. In his application of the law to the facts,  
there is no doubt that Shore J. was using the test as  
set out in Beloit when he stated, at para. 57:  
Based on the law, the question before the  
Court is whether a person skilled in the art  
was given such a clear direction that, by  
Page: 177  
reading and following the 875 patent (or its  
U.S. or French equivalents) would in every  
case and without possibility of error make a  
compound or pharmaceutical composition  
within the claims of the 777 patent (e.g. the  
bisulfate salt of clopidogrel).  
(c) Recent United Kingdom Jurisprudence  
[23] For the reasons that follow, and in light of  
recent jurisprudence, I am of the respectful opinion  
that the applications judge overstated the stringency  
of the test for anticipation that the exact invention”  
has already been made and publicly disclosed.  
[24] In the 2005 decision of the House of Lords  
in Synthon, Lord Hoffmann has brought some  
further clarity to the law of anticipation as  
understood since General Tire. His reference at  
para. 20 to the unquestionable authorityof Lord  
Westbury in Hills v. Evans (1862), 31 L.J. Ch.  
(N.S.) 457, at p. 463, makes it plain that his analysis  
does not depend on any change on English law  
flowing from the enactment of the Patents Act 1977  
(U.K.), 1977, c. 37, or the U.K.s adoption of the  
Convention on the Grant of European Patents, 1065  
U.N.T.S. 199 (entered into force October 7, 1977).  
He distinguishes between two requirements for  
anticipation that were not theretofore expressly  
considered separately, prior disclosure and  
enablement.  
[25] [In the 2005 decision of the House of Lords  
in Synthon, Lord Hoffmann] explains that the  
requirement of prior disclosure means that the prior  
patent must disclose subject matter which, if  
performed, would necessarily result in infringement  
of that patent, and states, at para. 22:  
If I may summarise the effect of these two  
well- known statements [from General Tire  
and Hills v. Evans], the matter relied upon as  
prior art must disclose subject matter which,  
if performed, would necessarily result in an  
infringement of the patent... It follows that,  
Page: 178  
whether or not it would be apparent to  
anyone at the time, whenever subject matter  
described in the prior disclosure is capable of  
being performed and is such that, if  
performed, it must result in the patent being  
infringed, the disclosure condition is  
satisfied.  
When considering the role of the person skilled in  
the art in respect of disclosure, the skilled person is  
taken to be trying to understand what the author of  
the description [in the prior patent] meant(para.  
32). At this stage, there is no room for trial and  
error or experimentation by the skilled person. He is  
simply reading the prior patent for the purposes of  
understanding it.  
[26] If the disclosure requirement is satisfied, the  
second requirement to prove anticipation is  
enablementwhich means that the person skilled  
in the art would have been able to perform the  
invention (para. 26).  
(1) Disclosure  
[74] As stated in Sanofi, in order for there to be disclosure of the  
619 Patent, the EP 214 application must have disclosed all the  
information that is needed for the Skilled Person, without inventive  
skill, to make the claimed invention, where the claimed invention  
necessarily infringes the prior disclosure. And, as stated in para 25  
in Sanofi, when considering the role of the person skilled in the  
art in respect of disclosure, the skilled person is taken to be trying  
to understand what the author of the description [in the prior  
patent] meant’ […]. At this stage, there is no room for trial and  
error or experimentation by the skilled person. He is simply  
reading the prior patent for the purposes of understanding it.  
Page: 179  
[368] Apotex referred the Court to and I accept what Justice Hughes said regarding the legal  
and evidentiary obligations of first and second persons in Allergan Inc v Canada (Health), 2012  
FC 767 [Allergan]:  
ISSUE #1: Who bears the burden?  
[42] As to the allegations of invalidity, the Patent Act, RSC  
1985, P-4, section 43(2) affords a presumption of validity;  
however, once a second person, here Apotex, puts in some  
evidence as to invalidity, the Court must determine the matter on  
the usual civil burden; namely, balance of probabilities. I repeat  
what I wrote in GlaxoSmithKline Inc v Pharmascience Inc, 2011  
FC 239 at paras 43 and 44:  
43  
OReilly J of this Court has summarized the  
question of burden of proof where the issue is  
invalidity in Pfizer Canada Inc. v. Apotex Inc., 2007  
FC 26, 59 CPR(4th) 183 (affd 2007 FCA 195,  
leave to appeal refused [2007] SCCANo. 371) at  
paragraphs 9 and 12:  
9
In my view, the burden on a  
respondent under the Regulations is an  
evidential burden-- a burden merely to  
adduce evidence of invalidity. Once it has  
discharged this burden, the presumption of  
validity dissolves and the Court must then  
determine whether the applicant has  
discharged its legal burden of proof. I  
believe this is what is meant in those cases  
where the Court has stated that the  
respondent must put its allegations into  
play. It must present sufficient evidence to  
give its allegations of invalidity an air of  
reality.  
...  
12  
To summarize, Pfizer bears the legal  
burden of proving on a balance of  
probabilities that Apotexs allegations of  
invalidity are unjustified. Apotex merely has  
an evidentiary burden to put its case into  
Page: 180  
playby presenting sufficient evidence to  
give its allegations of invalidity an air of  
reality. If it meets that burden, then it has  
rebuttedthe presumption of validity. I must  
then determine whether Pfizer has  
established that Apotexs allegations of  
invalidity are unjustified. If Apotex does not  
meet its evidential burden, then Pfizer can  
simply rely on the presumption of validity to  
obtain its prohibition order.  
44  
In Pfizer Canada Inc. v. Canada (Minister of Health), 2008  
FC 11, 69 C.P.R. (4th) 191, I said in respect of the same thing at  
paragraph 32:  
32 I do not view the reasoning of the two panels of  
the Federal Court of Appeal to be in substantial  
disagreement. Justice Mosley of this Court  
reconciled these decisions in his Reasons in Pfizer  
Canada Inc. v. Apotex Inc., [2007] F.C.J. No. 1271,  
2007 FC 971 at paragraphs 44 to 51. What is  
required, when issues of validity of a patent are  
raised:  
1.  
The second person, in its Notice of  
Allegation may raise one or more grounds  
for alleging invalidity;  
2.  
The first person may in its Notice of  
Application filed with the Court join issue on  
any one or more of those grounds;  
3.  
The second person may lead  
evidence in the Court proceeding to support  
the grounds upon which issue has been  
joined;  
4.  
The first person may, at its peril, rely  
simply upon the presumption of validity  
afforded by the Patent Act or, more  
prudently, adduce its own evidence as to the  
grounds of invalidity put in issue.  
5.  
The Court will weigh the evidence; if  
the first person relies only on the  
Page: 181  
presumption, the Court will nonetheless  
weigh the strength of the evidence led by the  
second person. If that evidence is weak or  
irrelevant the presumption will prevail. If  
both parties lead evidence, the Court will  
weigh all the evidence and determine the  
matter on the usual civil balance.  
6.  
If the evidence weighed in step 5 is  
evenly balanced (a rare event), the Applicant  
(first person) will have failed to prove that  
the allegation of invalidity is not justified  
and will not be entitled to the Order of  
prohibition that it seeks.  
[Emphasis added.]  
[369] The issue of anticipation came before this Court in an unusual manner.  
[370] Apotex raised anticipation in its NOA. Pfizer, as the Applicant in this proceeding,  
provided the Court with evidence of experts who had been instructed on anticipation  
(Drs. Atwood and Myerson). However, Pfizer did not address anticipation in its memorandum of  
fact and law. Instead, Pfizer took the position (in a footnote in its memorandum) that anticipation  
was not before the Court because Apotex had not filed evidence concerning the anticipation of  
any claim in the material it file responding to this application. The footnote added that Pfizer  
reserved the right to make submissions in response should Apotex pursue any additional issues  
at the hearing.”  
[371] At the hearing, Pfizer maintained its position that anticipation was not before the Court  
because Apotex had not dealt with the issue of anticipation in the evidence it filed for the  
Page: 182  
hearing. Pfizer also argued that the evidence Apotex relied on was of no value because Apotexs  
experts had not been instructed in the law of anticipation, or in terms of either disclosure or  
enablement, key concepts related to anticipation.  
[372] The resolution of this issue turns on the evidence: Abbott Laboratories v Apotex Inc,  
2007 FCA 153 at paras 9 and 10. In terms of the evidence before this Court, Apotex relied on the  
affidavit evidence of Dr. Steed and Dr. Bastin to give its allegation of anticipation an air of  
reality sufficient to displace the statutory presumption of validity set out in s 43(2) of the  
Patent Act.  
[373] However I am unable to accept this evidence for several reasons. First, as Pfizer correctly  
pointed out, neither Drs. Bastin nor Steed were instructed on the law of anticipation, and neither  
was instructed on either disclosure or enablement. I am unable to see how the Court may  
confidently accept what is stated by a scientific expert witness when he or she has no  
understanding of the legal meaning of the words or concepts at issue.  
[374] Second, the fact is that the evidence of both Dr. Steed and Dr. Bastin was not tendered in  
respect of anticipation; it was tendered in connection with the issues of obviousness and obvious  
to try.  
[375] The evidence of Dr. Steed that Apotex asks the Court to rely upon was tendered under the  
heading: X. Sixth mandate -Differences between inventive concepts of the claims of the 668  
Page: 183  
Patent and the state of the art and common general knowledge, subheading b. The state of the  
art and common general knowledge as of February 12, 2001, sub-subheading 2(ii) Patents  
disclosing different forms of ODV and formulations of ODV, and subheading d. Was  
inventive ingenuity required to overcome this difference.”  
[376] The evidence of Dr. Bastin that Apotex asks the Court to rely on regarding anticipation,  
was likewise not given in respect of anticipation (like Dr. Steed, he nowhere uses the word), but  
was instead tendered under the heading: VI. Would the skilled person have required inventive  
ingenuity to arrive at the inventive concept of claims 1, 2, 4 to 9, 20, 21, 23 to 28, and 31 to 33 of  
the 668 Patent?, subheading 2. The common general knowledge of the skilled person and the  
state of the art, subsub heading I. ODV, its salts, dosage forms, and uses, and X. The  
affidavits of Drs. Myerson, Atwood, Polli and Blier, subheading 4. The opinion that  
compositions of ODV succinate and their preparation would not be obvious, and subheading 5.  
The opinion that the use of ODV succinate was not obvious.  
[377] Thus, their evidence was not tendered in respect of anticipation but in connection with  
the issue of obvious to try and obviousness. This is underscored by the fact that neither  
Drs. Bastin nor Steed use the word anticipationanywhere in their evidence.  
[378] In this connection, I note that Dr. Bastin uses the words discloseand enablein his  
affidavit; likewise Dr. Steed also uses the word disclosed. However, I was given no reason to  
accept their evidence as useful to the Court given that neither was instructed in respect of  
Page: 184  
anticipation, disclosure or enablement; on this basis alone what they said is not acceptable to  
assist the Court in its anticipation inquiry.  
[379] Use of such words in parts of affidavits directed to obviousness was also insufficient to  
put Pfizer on notice that Apotex was going to use that evidence in support of its allegation of  
anticipation. Apotexs failure to file proper evidence on anticipation led Pfizer to reasonably  
conclude, at the time it filed its memorandum, that it did not need to deal with anticipation.  
Therefore Pfizer was not in breach of Rule 70(1)(c) of the Rules of the Federal Courts, SOR/98-  
106 when it filed its memorandum.  
[380] Apotex says it may rely on this alleged evidence of anticipation notwithstanding these  
defects; I disagree for two reasons. First, I am not prepared to accept as of assistance to the Court  
evidence on the issue of anticipation offered by a witness not instructed on the law of  
anticipation, a point I have already made. Secondly, in my respectful view, neither party should  
be allowed to imbed critical evidence on one issue into material filed in relation to another and  
different issue, and then, after all the evidence including reply affidavits and cross-examinations  
is complete, rely on the imbedded evidence to attack the patent.  
[381] To rule otherwise would not only allow expert evidence in respect of matters where the  
experthas no proper basis on which to give an opinion. It would reward litigation by surprise.  
It would also encourage the playing of hide-and-seek and guessing games. This is not just a  
question of headings as Apotex argued, but a matter of basic fairness. All parties to a NOC, not  
Page: 185  
to mention the Court, are entitled to proper pleadings including affidavits to eliminate such  
conduct so as to best ensure efficient determination of the issues.  
[382] That said, I agree with Apotex that Pfizer may not split its case by declining to deal with  
the merits of an issue in its memorandum and then dealing with that issue in oral reply at the end  
of the hearing. Here, Pfizer argued the absence of properly instructed expert evidence in its  
memorandum. In oral argument in chief Pfizer again pointed to its own expert evidence on the  
issue of anticipation. Apotex in response took the Court through its alleged evidence on  
anticipation, taking the position it had thereby put anticipation into play and was entitled to  
succeed given Pfizers position. In reply, Pfizers counsel dealt with Apotexs submissions and  
then as I understood it, attempted to engage the Court on the merits of an anticipation argument,  
to which Apotex objected. I ruled I would hear Pfizers argument, reserving on what I would do  
with it. In the circumstances, I will not rely on Pfizers reply argument on the merits of  
anticipation because to do so would allow case splitting.  
[383] In my view, once Apotex filed its memorandum dealing with anticipation, which made it  
plain that anticipation was still in issue, Pfizer could no longer proceed on the assumption that  
anticipation was not in issue. That anticipation was still in issue was further confirmed in a joint  
letter to the Court from counsel dated June 9, 2017, the Friday before the hearing which started  
on the 12th. Pfizer could have sought leave to file a supplementary memorandum after it  
received Apotexs responding memo, or taken other steps, but did not. I am not saying that such  
permission would have been granted or dismissed because the point was not argued.  
Page: 186  
[384] In the end, I am asked by Apotex to rely on Justice de Montignys [as he then was]  
decision in Eli Lilly Canada Inc v Mylan Pharmaceuticals, 2015 FC 125 at para 79, and accept  
the evidence of Drs. Steed and Bastin, as a substitute for properly instructed and acceptable  
expert evidence on anticipation notwithstanding the other circumstances of this case.  
[385] In the particular circumstances of this case, and for the reasons already given, I am not  
prepared to do so.  
[386] Apotex also relied on the allegations of anticipation it made in its NOA as evidence to  
displace the statutory presumption. However, and with respect, while allegations of non-  
infringement in a NOA are presumed to be true: Merck Frosst Canada Inc v Canada (Minister of  
National Health and Welfare), [1994] FCJ No 662 at paras 23-24 (FCA) (QL), leave to appeal to  
SCC refused, [1994] SCCA No 330 (SCC) (QL)), I have no authority for the proposition that  
allegations of anticipation in a NOA benefit from the same presumption or are evidencefor the  
purposes of the factors set out above in the Allergan decision.  
[387] Apotex also relied on the WO 851 Patent in support of its allegation of anticipation. I  
have already discussed the WO 851 Patent, and found that as prior art it did not disclose the  
Form I ODV succinate at issue in Claims 8 and 9. Since Claims 33, 43 and 44 depend on claims  
8 and 9, the WO 851 Patent does not assist Apotex on the issue of anticipation.  
Page: 187  
[388] Therefore as I see it, and with respect, this situation gives rise to the 5th factor in the  
passage of Justice Hughes in Pfizer Canada Inc v Canada (Minister of Health), 2008 FC 11 at  
para 32, cited in Allergan, above, which states that: [T]he Court will weigh the evidence; if the  
first person relies only on the presumption, the Court will nonetheless weigh the strength of the  
evidence led by the second person. If that evidence is weak or irrelevant the presumption will  
prevail.”  
[389] Pfizer relies on the presumption. Because I have not accepted the evidence given by the  
second person (Apotex), it must be considered weak in terms of that 5th factor. Therefore the  
presumption of validity will and does prevail.  
[390] I find on a balance of probabilities that Apotexs allegation in respect of anticipation is  
not justified.  
8.  
Double patenting  
[391] It is common ground that the Patent Act only entitles an inventor to a single patent for  
each invention. Thus, a second patent will fail for double patenting if its claims are  
(i) coterminouswith the claims of a prior patent, sometimes called same inventiondouble  
patenting, or, (ii) if its claims lack ingenuity over the claims of an earlier patent (i.e., the claims  
are not patentably distinct), sometimes described as obviousnessdouble patenting.  
[392] The Supreme Court of Canada said in Whirlpool Corp v Camco Inc, 2000 SCC 67:  
 
Page: 188  
63  
The prohibition against double patenting relates back to the  
evergreenproblem mentioned at the outset. The inventor is only  
entitled to apatent for each invention: Patent Act, s. 36(1). If a  
subsequent patent issues with identical claims, there is an improper  
extension of the monopoly. 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.  
The question is how identicalthe claims must be in the  
subsequent patent to justify invalidation.  
64  
The Federal Court of Appeal has adopted the test that the  
claims must be identical or conterminous: Beecham Canada Ltd.  
v. Procter & Gamble Co. (1982), 61 C.P.R. (2d) 1, at p. 22. This  
verbal formulation derives from an editorial comment by Dr. H. G.  
Fox, Q.C., on Lovell Manufacturing Co. v. Beatty Bros. Ltd.,  
reported at (1962), 23 Fox Pat. C. 112, at pp. 116-17:  
Letters patent are not granted at pleasure, but for a  
term of years and the grant of a second patent with  
respect to the same subject-matter would be void  
under this statute [6 Henry VIII, c. 15, 1514] and by  
the Statute of Monopolies, as well as at common  
law and by the terms of section 28(1)(b) of the  
Canadian Patent Act. But for this purpose the  
subject-matter of the two grants must be identical.  
A subsequent claim cannot be invalidated on the  
ground of prior claiming unless the two claims are  
precisely conterminous.  
65  
This branch of the prohibition on double patenting is  
sometimes called same inventiondouble patenting. Given the  
claims construction adopted by the trial judge it cannot be said that  
the subject matter of the 734 patent is the same or that the claims  
are identical or conterminouswith those of the 803 patent.  
66  
There is, however, a second branch of the prohibition  
which is sometimes called obviousnessdouble patenting. This is  
a more flexible and less literal test that prohibits the issuance of a  
second patent with claims that are not patentably distinctfrom  
those of the earlier patent. In Commissioner of Patents v.  
Farbwerke Hoechst Aktiengesellschaft Vormals Meister Lucius &  
Bruning, [1964] S.C.R. 49, the issue was whether Farbwerke  
Hoechst could obtain a patent for a medicine that was a diluted  
version of a medicine for which it had already obtained a patent.  
The claims were neither identical nor conterminous. Judson J.  
Page: 189  
nevertheless held the subsequent patent to be invalid, explaining at  
p. 53:  
A person is entitled to a patent for a new, useful and  
inventive medicinal substance but to dilute that new  
substance once its medical uses are established does  
not result in further invention. The diluted and  
undiluted substance are but two aspects of exactly  
the same invention. In this case, the addition of an  
inert carrier, which is a common expedient to  
increase bulk, and so facilitate measurement and  
administration, is nothing more than dilution and  
does not result in a further invention over and above  
that of the medicinal itself. [Emphasis added.]  
67  
In Consolboard, supra, Dickson J. referred to Farbwerke  
Hoechst as the main authority on double patenting(p. 536)  
which stood for the proposition that a second patent could not be  
justified unless the claims exhibited novelty or ingenuityover  
the first patent:  
Judson J. for the Court said that the second process  
involved no novelty or ingenuity, and hence the  
second patent was unwarranted.  
68  
It is on this second branch of obviousnessdouble  
patenting that the appellants rest their case against all of the claims  
of the 734 patent except the continuous driveclaims which they  
concede to be valid albeit they contest infringement.  
[393] The Federal Court of Appeal in Pharmascience Inc v Sanofi-Aventis Canada Inc, 2006  
FCA 229 [Pharmascience] also discussed the two concepts of double patenting:  
68  
The jurisprudence has so far identified two categories of  
double patenting. In the first category, same invention patenting,  
two patents are the same or have an identical or conterminous  
claim. The second category, obviousness double patenting, is  
somewhat broader. In obviousness double patenting, the claims of  
the patents are not identical or conterminous, but the later patent  
has claims that are not patentably distinct from the other patent, or  
involve no novelty or ingenuity.  
Page: 190  
[394] Recently, Justice Manson of this Court set out the law of double patenting in Bristol-  
Myers Squibb Canada v Apotex Inc, 2017 FC 296:  
B. Double Patenting  
(1)  
Law  
[203] Section 36(1) of the Patent Act states [a] patent shall be  
granted for one invention only but in an action or other proceeding  
a patent shall not be deemed to be invalid by reason only that it has  
been granted for more than one invention. The patent bargain is in  
the interest of both the patentee and the public only if the patent  
owner acquires real protection in exchange for disclosure, and the  
public does not for its part surrender a more extended monopoly  
than the statutory [20] years from the date of the patent grant”  
(Whirlpool Corp v Camco Inc, 2000 SCC 67 at para 37  
[Whirlpool]).  
[204] Double patenting occurs when two patents are issued to the  
same inventor, and the subsequent patent has identical claims to  
the first (Whirlpool, above, at para 63). Determining whether  
double patenting has occurred requires the Court to compare the  
claims, not the disclosures, of both patents and determine whether  
the patents are (1) identical or coterminous; or (2) obvious, such  
that the claims of the second patent are not patentably distinct’  
from those of the earlier patent(Whirlpool at paras 63 to 66).  
[205] A second patent cannot be justified unless the claims  
exhibit novelty or ingenuity over the first patent (Whirlpool at para  
67).  
[395] In its memorandum, Apotex puts its case this way:  
66. The Patent Act only entitles an inventor to a single patent  
for each invention. A second patent will fail for double patenting if  
its claims are coterminouswith the claims of a prior patent, or, if  
its claims lack ingenuity over the claims of an earlier patent. In the  
case of obviousness-type double patenting, the question is whether  
the skilled person reading the first patent together with his or her  
common general knowledge, would arrive at the claims of the  
second patent without exercising inventive ingenuity.  
Page: 191  
67.  
The 540 patent issued on January 10, 2010 and is the  
corresponding Canadian equivalent to US 186 discussed above.  
Like the patent, the 540 patent is owned by Wyeth.  
68.  
Claim 21 of the 540 patent is specifically directed to ODV  
or a pharmaceutically acceptable salt thereof. The skilled person  
would have understood that ODV-S is included within the scope of  
this claim. Further, the disclosure of the 540 patent specifies that  
succinate salts are among the pharmaceutically acceptable salts”  
of its compounds. Practising these claims will yield ODV-S Form  
I. As such, at all material times, claims 8 and 9 of the patent  
represent double patenting over claim 21 of the 540 patent.  
[396] Pfizer in its memorandum said:  
54. No Double Patenting over CA 540. Apotex alleges that  
claims 8, 9, 33, 43 and 44 of the 668 Patent are invalid for double  
patenting over claim 21 of the 540 Patent. The 540 Patent discloses  
a class of chemical compounds which includes ODV. Claim 21  
covers ODV or a pharmaceutically acceptable salt thereof. The  
claim does not mention which, if any, of the possible salts of ODV  
would be contemplated, and does not mention which solid state  
forms of those salts would be included. Claim 21 is not a claim to  
the same inventionas any of claims 8, 9, 33, 43 or 44, which are  
claims to new solid-state forms, uses and formulations of a  
particular salt form of ODV.  
55.  
For the same reasons addressed above in respect of  
obviousness, there is no obviousness-type double patenting over  
claim 21 of the 540 Patent. A skilled person could not know from  
claim 21 what the properties of any particular salt form of ODV  
may be. They would not know whether (or how) it could be made  
as a crystalline solid, what crystalline solids may exist, or whether  
any particular salt or solid form would have properties amenable to  
formulation and development (including as a SR formulation). The  
only salt form of ODV taught by the 540 Patent is the fumarate. No  
properties (beyond a melting point) of that salt are provided. The  
patent discloses the possibility that other pharmaceutically  
acceptable salts of the compounds of the inventioncould exist,  
but there is no specific indication that the succinate salt of ODV  
could be formed, would be crystalline or would have any of the  
properties disclosed in the 668 Patent.  
Page: 192  
[397] It is not disputed that Claim 21 in the earlier CA 540 Patent, which was owned by a  
Pfizer company, covers ODV or a pharmaceutically acceptable salt thereof. The claim does not  
state which, if any, of the possible salts of ODV would be contemplated, and does not mention  
which solid state forms of those salts would be included. In my view, and as I have construed  
them, there is no coterminoussometimes called same inventiondouble patenting involved in  
Claims 8 or 9 of the 668 Patent in relation to Claim 21 of the CA 540 Patent.  
[398] Therefore the issue is whether the 668 Patent lacks ingenuity or, put another way,  
constitutes obviousness-type double patenting. Thus the question - and on this the parties agree -  
is whether the Skilled Person reading the relevant claim of the CA 540 Patent (together with his  
or her common general knowledge) would arrive at the claims of the 668 Patent without  
exercising inventive ingenuity. In my view the Skilled Person would not.  
[399] Apotexs only witness who gave evidence on double patenting was Dr. Bastin. Pfizer  
observes that while Apotex argues that all solid state forms of all salts were monopolized by the  
CA 540 Patent, Dr. Bastin did not give that evidence. Rather, Dr. Bastin testified that nothing in  
the prior art tells one how to prepare Form I ODV succinate specifically.  
[400] Dr. Bastin gave the following evidence in cross-examination at pages 157 and 158:  
Q.  
Right, but nothing in the prior art tells you how to prepare  
Form I ODV succinate specifically?  
A.  
Not specifically, yeah.  
Page: 193  
[401] Insofar as his affidavit is concerned, while Dr. Bastin deposed to his opinion that claim  
21 of the 540 Patent includes within its scope the compound ODV succinate, his evidence  
relating to CA 540 and its Claim 21 does not refer to Form I ODV succinate which I have found  
to be the inventive concept covered by Claims 8 and 9. Dr. Bastins testimony, nothing in the  
prior art, which includes CA 540, tells one how to prepare Form I ODV succinate specifically. In  
my view this supports the proposition that Claims 8 and 9 exhibit novelty or ingenuity.  
[402] In this connection, I accept that a Skilled Person could not know from Claim 21 what the  
properties of any particular salt form of ODV might be. He or she would not know whether (or  
how) it could be made as a crystalline solid, what crystalline solids may exist, or whether any  
particular salt or solid form would have properties amenable to formulation and development  
(including a sustained release formulation). Nothing in Claim 21 pointed to specifically to Form  
I ODV succinate, nor indeed even to ODV succinate as a salt. The only salt form of ODV  
specifically taught by the 540 Patent is the fumarate, and no properties (beyond a melting point)  
of that salt are provided. The CA 540 Patent discloses the possibility that other pharmaceutically  
acceptable salts of the compounds of the inventioncould exist, but there is no specific  
indication that the succinate salt of ODV could be formed, would be crystalline or would have  
any of the properties disclosed in the 668 Patent.  
[403] On further review of the evidence in this case including the invention story and  
knowledge of the Skilled Person as I have found them in my discussion of obviousness, I am  
persuaded that the Skilled Person reading Claim 21of the CA 540 Patent (together with his or her  
Page: 194  
common general knowledge) would not arrive at Claims 8 and or 9 of the 668 Patent, i.e., Form I  
ODV succinate, without exercising inventive ingenuity. Put another way, per Pharmascience at  
para 68, Claims 8 and 9 are patentably distinct from the Claim 21 in CA 540, because it may not  
be said of Claims 8 and 9 that they involve no novelty or ingenuity.  
[404] For the record, I note that both Pfizer and Apotex agree that the 668 Patent is not a  
selection patent.  
[405] Therefore I am satisfied on a balance of probabilities that Apotexs allegation of double  
patenting is not justified.  
IX.  
Conclusions  
[406] I have found on a balance of probabilities that Apotexs allegations of invalidity due to  
obviousness, inutility, anticipation, overpromising and double patenting together with Apotexs  
allegation of non-infringement are not justified. Therefore Pfizer will have its requested Order of  
prohibition.  
X.  
Costs  
[407] Costs follow the cause therefore costs are payable by Apotex to Pfizer. The parties have  
agreed on directions regarding costs, which agreement I find reasonable, such that directions  
   
Page: 195  
shall issue as set out in Schedule A - Agreed Terms of Costs Order attached to these Reasons and  
Judgment.  
XI.  
Confidential Reasons  
[408] These reasons contain information subject to a Protective Order and are therefore marked  
Confidential. The Parties shall have 20 days to consult with one another and advise the Court  
what if any portions they wish redacted, failing which these reasons will become the public  
reasons and be placed on the public file.  
 
Page: 196  
JUDGMENT  
THIS COURTS JUDGMENT is that:  
1. The Application is granted.  
2. The Minister of Health is prohibited from issuing a Notice of Compliance in  
respect of a Notice of Allegation sent by Apotex Inc. to Pfizer Canada Inc.  
previously Wheth LLC, dated January 21, 2016, until the expiry of Canadian  
Patent No. 2,436,668.  
3. Apotex Inc. shall pay Pfizer its costs of this application in accordance with  
Schedule A - Agreed Terms of Costs Order attached hereto.  
4. The Parties shall have 20 days to consult with one another and advise the Court  
what if any portions of this Confidential Judgment and Reasons they wish  
redacted, failing which these reasons will become the public reasons and placed  
on the public file.  
“Henry S. Brown”  
Judge  
Page: 197  
Schedule A - Agreed Terms of Costs Order  
Pfizer is awarded its costs of this Application in accordance with the following directions,  
provided that the following directions in no way modify or supersede any existing Orders or  
Directions with respect to costs for particular motions or steps before the hearing of this  
Application.  
a) Costs are to be assessed at the middle of Column IV of Tariff B;  
b) No costs are recoverable for in-house counsel, law clerks, students and support staff;  
c) Costs are recoverable only for those experts who provided affidavits or reports that  
were filed in the proceedings (the allowable experts);  
d) The hourly rate for allowable experts shall not exceed the hourly rate of senior  
counsel;  
e) Fees paid to allowable experts for time not spent preparing the experts own  
affidavit/report or preparing for the experts own cross-examination are recoverable  
only where it is demonstrated that it was reasonable and necessary to provide technical  
assistance to counsel;  
f) Counsel fees shall be assessed on the basis of:  
i.  
ii.  
one senior and one junior counsel at the hearing;  
one senior and one junior counsel in conducting cross-examinations; and  
one senior counsel in defending cross-examinations;  
iii.  
g) Travel and accommodation expenses will be assessed on the basis of economy air  
fares and single rooms; and  
h) Photocopying costs will be assessed at $0.25 per page, and the number of recoverable  
copies shall be limited to that which is reasonable and necessary.  
FEDERAL COURT  
SOLICITORS OF RECORD  
T-402-16  
DOCKET:  
PFIZER CANADA INC. and WYETH LLC v APOTEX  
INC and THE MINISTER OF HEALTH  
STYLE OF CAUSE:  
TORONTO, ONTARIO  
PLACE OF HEARING:  
DATE OF HEARING:  
JUNE 12, 2017  
BROWN J.  
ORIGINAL AND CORRECTED  
CONFIDENTIAL JUDGMENT  
AND REASONS:  
AUGUST 22, 2017  
BROWN J.  
DATED:  
PUBLIC JUDGMENT AND  
REASONS:  
SEPTEMBER 22, 2017  
DATED:  
APPEARANCES:  
Andrew Shaughnessy  
Andrew Bernstein  
Rachael Saab  
Aria Laskin  
Nicole Mantini  
FOR THE APPLICANTS  
FOR THE RESPONDENTS  
Andrew Brodkin  
Richard Naiberg  
SOLICITORS OF RECORD:  
Torys LLP  
Barristers and Solicitors  
Toronto, Ontario  
FOR THE APPLICANTS  
FOR THE RESPONDENTS  
Goodmans LLP  
Barristers and Solicitors  
Toronto, Ontario  


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