Date: 20170922  
Docket: T-1399-15  
Citation: 2017 FC 777  
Ottawa, Ontario, September 22, 2017  
PRESENT: The Honourable Mr. Justice Brown  
BETWEEN:  
PFIZER CANADA INC. and WYETH LLC  
Applicants  
and  
TEVA CANADA LIMITED 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................................................................................................................ 4  
II. Procedural Note ...................................................................................................................... 5  
III. Summary of Conclusions........................................................................................................ 6  
IV. Facts ........................................................................................................................................ 6  
1.  
Witnesses....................................................................................................................................6  
A. Pfizer..................................................................................................................... 6  
Page: 2  
B. Teva....................................................................................................................... 8  
Background.................................................................................................................................8  
The Invention Story .................................................................................................................11  
Invention story in more detail: the evidence of Pfizer’s Dr. Shah........................................15  
Experimentation with ODV fumarate.....................................................................................18  
Attempt to form pro-drug of ODV..........................................................................................20  
Attempt to form an acceptable salt of ODV...........................................................................21  
Polymorph and crystal screening............................................................................................25  
Solubility...................................................................................................................................26  
The Preparation of ODV Succinate ........................................................................................27  
Permeability and bioavailability testing .................................................................................29  
||||||||||||||||||||||.......................................................................................................30  
Rat perfusion test......................................................................................................................30  
Beagle dog testing....................................................................................................................34  
Human Testing.........................................................................................................................36  
Solid state forms: crystallinity, amorphous solids, polymorphs ...........................................39  
Polymorph screening and subcontracting polymorph screening to SSCI............................40  
Dr. Aeri Park at SSCI...............................................................................................................42  
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||| ........................................49  
Melting points and differential scanning calorimetry (DSC)................................................49  
Further temperature studies and amorphous form .................................................................50  
Hygroscopicity testing (a test relevant to drug stability).......................................................51  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||.....52  
|||||||||||||| (Crystal Form “C”)......................................................................................52  
|||||||||||||||||||||||| (Crystal Form “D”)....................................................................53  
Work on other salt candidates and screens.............................................................................55  
2.  
3.  
4.  
5.  
6.  
7.  
8.  
9.  
10.  
11.  
12.  
13.  
14.  
15.  
16.  
17.  
18.  
19.  
20.  
21.  
22.  
23.  
24.  
25.  
26.  
V. Issues..................................................................................................................................... 56  
VI. Statutory provisions and burden of proof ............................................................................. 57  
Page: 3  
VII. Analysis................................................................................................................................. 58  
1.  
2.  
3.  
Relevant Dates..........................................................................................................................58  
Claims Construction.................................................................................................................59  
Obviousness..............................................................................................................................64  
A. Introductory comments and summary ................................................................ 64  
B. The obviousness inquiry ..................................................................................... 65  
C. Federal Court of Appeal Jurisprudence .............................................................. 76  
D. Analysis of Obviousness..................................................................................... 82  
E.  
F.  
Identify the notional “person skilled in the art”.................................................. 82  
Identify the relevant common general knowledge of the Skilled Person ........... 83  
G. Identify the inventive concept of the claim in question or if that cannot readily be  
done, construe it ........................................................................................................... 97  
i. Claims 8 and 9................................................................................................ 98  
ii. Claim 33....................................................................................................... 100  
iii.Claim 43....................................................................................................... 101  
iv. Claim 44....................................................................................................... 102  
H. 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 .................................................................................................................... 103  
i. Claims 8 and 9.............................................................................................. 103  
ii. Claim 33....................................................................................................... 104  
iii.Claim 43 and 44 ........................................................................................... 105  
I.  
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?.......................................................... 106  
i. Apply the definition of obvious before Sanofi............................................. 107  
ii. Consider the doctrine of obvious to try........................................................ 111  
J.  
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? ... 113  
Page: 4  
K. 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?.................................. 125  
L.  
Is there a motive provided in the prior art to find the solution the patent  
addresses?................................................................................................................... 127  
M. The 668 Patent is not a selection patent............................................................ 129  
N. What is the course of conduct followed which culminated in making the  
invention? ................................................................................................................... 131  
i. Conclusions on obvious to try regarding Claims 8 and 9 ............................ 134  
ii. Conclusions on obvious to try regarding Claims 33, 43 and 44 .................. 134  
O. Consideration of guidance of obvious to try analysis set out in Sanofi............ 135  
P.  
Conclusion on obviousness............................................................................... 135  
4.  
Utility......................................................................................................................................136  
A. First identify the subject-matter of the invention as claimed in the patent, and  
second, is that subject-matter useful – is it capable of a practical purpose (i.e. an actual  
result).......................................................................................................................... 141  
B. Is Form I ODV succinate, the subject matter of Claims 8 and 9, useful - is it  
capable of a practical purpose (i.e. an actual result)?................................................. 141  
C. Are the subject matters of Claims 33, 43 and 44 useful – are they capable of a  
practical purpose (i.e. an actual result)?..................................................................... 145  
VIII.Conclusion .......................................................................................................................... 147  
IX. Costs.................................................................................................................................... 148  
X. Confidential Reasons .......................................................................................................... 148  
***  
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 Teva Canada Ltd., [Teva  
 
Page: 5  
or Respondent] to Pfizer Canada Inc., previously Wyeth LLC [Pfizer or Wyeth or Applicant],  
dated July 10, 2015, 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]  
Teva alleges that Claims 8, 9, 33, 43 and 44 of the 668 Patent fail for obviousness and  
lack of utility. Teva also alleges that the 668 Patent is an invalid selection patent. While Teva  
raised non-infringement and anticipation in its NOA, it withdrew those allegations.  
[3]  
Teva also withdrew, on the 3rd day of this 5 day NOC, its allegation that Pfizer obtained  
the 668 patent as a result of having made wilfully misleading statements in its patent application,  
i.e., conduct tantamount to fraud, contrary to s 53 of the Patent Act, RSC 1985, c P-4.  
II.  
Procedural Note  
[4]  
As a procedural note, this case was argued before I heard argument in Pfizer Canada Inc  
and Wyeth LLC v Apotex Inc and The Minister of Health, in respect of which I will deliver  
reasons and judgment later today, 2017 FC 774. These two cases involve different NOAs filed  
by different second persons (Teva and Apotex), against the same first person (Pfizer) in respect  
of the same 688 Patent. While the invention story is essentially the same in both, the grounds of  
invalidity differ. 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 resulting in  
additional repetition.  
 
Page: 6  
As guidance for those reading both decisions, I should note that while obviousness and  
[5]  
inutility are raised in both proceedings, Teva did not argue non-infringement, anticipation or  
double patenting as Apotex did in its proceeding. The parties in this Teva proceeding agree on  
the constructions of Claims 8 and 9, but there was no agreement on claims construction in the  
Apotex proceeding. Apotex in its proceeding also raised overpromising arising out of  
subsection 27(3) of the Patent Act as a ground of invalidity, an argument that Teva did not  
advance in this case.  
III.  
Summary of Conclusions  
[6]  
In the reasons that follow I find on a balance of probabilities that Teva’s allegations of  
invalidity due to obviousness and inutility are not justified. Therefore, Pfizer will have its Order  
of prohibition, together with costs on terms the parties have agreed upon.  
IV.  
1.  
Facts  
Witnesses  
A. Pfizer  
[7]  
Dr. 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 90s 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  
       
Page: 7  
forms of ODV), as well as later clinical research on ODV succinate and PRISTIQ. Dr. Shah is a  
named inventor on the 668 Patent. He was offered as a fact witness.  
[8]  
Dr. Allan Myerson is a Professor of the Practice of Chemical Engineering at the  
Massachusetts Institute of Technology (“MIT”). He is an expert in crystallization and the  
crystallization of pharmaceutical solids. He was on the SSCI advisory board from 2001 to 2006.  
He previously provided evidence regarding the corresponding US patent.  
[9]  
Dr. Aeri Park is a former Principal at SSCI, Inc., the research laboratory hired by Wyeth  
to conduct polymorph and crystal 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. She is one of the named inventors on the 668 Patent.  
Dr. Park was offered as a fact witness.  
[10] Dr. Leonard Chyall is the President of Chyall Pharmaceutical Consulting, LLC. He was  
formerly a Director at SSCI Inc. and had no direct involvement in the ODV succinate project. He  
trained under one of the inventors of the 668 Patent. He is an expert in solid state chemistry and  
has expertise in salt and polymorph screening and in the experimental and analytical techniques  
used to identify and characterize solid forms.  
[11] Dr. 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  
Page: 8  
standards for oral dosage forms. He is an expert in pharmaceutics, pharmacokinetics and  
bioavailability.  
B. Teva  
[12] Dr. Fakhreddin Jamali is a Professor in the Faculty of Pharmacy and Pharmaceutical  
Sciences at the University of Alberta. He teaches, researches and practices in the field of  
pharmacy and pharmaceutical sciences. He has expertise in clinical pharmacology, including  
matters of pharmacokinetics, bioavailability and bioequivalence.  
[13] Dr. Eugene F. Fiese is a consultant with Fiese Pharmaceutics Consulting. Dr. Fiese is a  
pharmaceutical chemist expert in the areas of preformulation, pharmaceutics research and dosage  
form development.  
[14] Dr. Daniel Z. Lieberman is a Professor of Psychiatry and Behavioral Sciences and  
Clinical Director at George Washington University. He is a clinician who teaches, researches and  
practices psychiatry and has particular expertise in the treatment of mood disorders including  
depression.  
2.  
Background  
[15] The 668 Patent concerns a drug called o-desmethyl-venlafaxine, henceforth referred to as  
ODV. ODV is a serotonin and norepinephrine reuptake inhibitor [SNRI] which is indicated for  
the treatment of depression. ODV works by simultaneously inhibiting the reuptake of both  
   
Page: 9  
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. 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. Pfizer argues and as will be  
seen, I have accepted that Form I ODV succinate is the subject of Claims 8 and 9, on which  
Claims 33, 43 and 44 depend.  
[16] ODV is an active metabolite of ODV’s parent drug, venlafaxine. ODV is called a  
metabolite because when venlafaxine is administered, it is chemically modified in the body to  
form ODV; it is ODV that is responsible for delivering some or all of the pharmacological effect.  
[17] It is common ground that ODV itself and its use as an antidepressant have been known  
for some time. Venlafaxine had been previously approved to treat depression, and was marketed  
by Wyeth and now Pfizer, Wyeth’s successor. Wyeth had ODV in hand since at least 1990.  
Wyeth marketed ODV, as the known metabolite of venlafaxine, under the names EFFEXOR and  
EFFEXOR XR. EFFEXOR is the immediate release version of venlafaxine (which converts in  
the body to ODV); EFFEXOR XR is the extended release version of venlafaxine (which also  
converts in the body to ODV). ODV is thus the API in both EFFEXOR and EFFEXOR XR.  
[18] Both EFFEXOR and EFFEXOR XR contain venlafaxine hydrochloride which is a salt;  
venlafaxine hydrochloride is henceforth simply referred to as venlafaxine.  
Page: 10  
[19] ODV and “pharmaceutically acceptable salt forms thereof” were claimed in both US  
Patent No. 4,535,186 (US 186) Claim 22, issued in 1985, and in Canadian Patent No. 1,248,540  
(CA 540), Claim 21, issued in 1989. CA 540 was granted to a predecessor company of the  
Applicant Wyeth, which predecessor company is also shown as an assignee of US 186.  
[20] “Pharmaceutically acceptable salts” as the term is used in US 186 and CA 540, are made  
by reacting an acid and a base. ODV is a base; therefore, to make a salt an appropriate acid is  
required for such a reaction. Both US 186 and CA 540 claim ODV succinate as one of 11  
“illustrative” pharmaceutically acceptable salts, and therefore include reference to reacting ODV  
with succinic acid. However, there is no suggestion that ODV succinate had ever been made, nor  
that a crystalline salt ODV succinate had ever been made, nor that Form I ODV succinate had  
ever been made it was made by Wyeth.  
[21] In addition to disclosure in the Canadian (CA 540) and American (US 186) patents just  
mentioned, it is also 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. Again there is no suggestion  
that ODV succinate had ever been made, nor that a crystalline salt ODV succinate had ever been  
made, nor that Form I ODV succinate had ever been made before it was made by Wyeth.  
[22] The prior art disclosed that venlafaxine as EFFEXOR or EFFEXOR XR and their  
metabolite ODV were useful to treat depression.  
Page: 11  
[23] Depression is and was also well known to be serious medical condition that can be and is  
often debilitating to those who suffer from it. 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.  
3.  
The Invention Story  
[24] The essence of the inventive story is also not generally in dispute although aspects of it  
are; the parties disagree on its characterization, and how the inventive story relates to the  
obviousness and obvious to try and other principles in patent law. The inventive story is also  
relevant in the dispute over utility. In my view it warrants being set out in some detail; I will first  
summarize it and then set it out in more detail.  
[25] The inventive story as I have found it is generally drawn from the affidavit of Dr. Shah  
who was at Wyeth at the time and who was in charge of commercializing ODV generally and  
then commercializing ODV succinate. The inventive story is also taken from the affidavit of  
Dr. Park who was in charge of polymorph screening of ODV succinate at a specialized company  
that performed polymorph screening for Wyeth, namely, SSCI, Inc. [SSCI].  
[26] 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 to which they depose. I appreciate that  
they are both named inventors on the 668 Patent, but am not persuaded this affected their  
evidence whether by affidavit or in cross-examination.  
 
Page: 12  
[27] Wyeth, now Pfizer, had venlafaxine and also knew that ODV was an active metabolite of  
venlafaxine. Wyeth through a predecessor company (together referred to as Wyeth) and Pfizer  
marketed venlafaxine as EFFEXOR and EFFEXOR XR. EFFEXOR delivered venlafaxine  
immediately, but for many patients 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 was better for many  
patients 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 extended or 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.  
[28] Wyeth’s 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, and in  
particular on the liver, to be converted into ODV, venlafaxine’s metabolite, which then acted as  
the anti-depressant in the body and more particularly in the brain.  
[29] The new ODV drug which 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 an oral dose involves permeating the GI tract.  
Page: 13  
[30] The searched-for new ODV drug had to be a stable, that is, it had to be 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.  
[31] The searched-for drug had to be a drug that would dissolve in the gastrointestinal [GI]  
tract i.e., 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 body’s systems and in particular, in the  
brain, i.e., it had to be a drug that was permeable and bioavailable.  
[32] 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.  
[33] In summary, over some two years - with greatly increased activity towards the end -  
experimentation and drug development was conducted, initially by Wyeth, and then by Wyeth  
together with I consider a specialized contract laboratory, SSCI. Employees of both Wyeth and  
SSCI are named inventors on the 668 Patent.  
[34] Wyeth and SSCI eventually identified a solid crystalline form of ODV that appeared to  
be stable, soluble 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  
Page: 14  
is common ground that this crystalline form is a new composition of matter that was never made  
or disclosed before it was created by Wyeth.  
[35] In this connection it is worth noting that while Teva alleged anticipation in its NOA, it  
subsequently withdrew that allegation. Therefore, in this proceeding it is not disputed that Form I  
ODV succinate is a “new” composition of matter per s 2 of the Patent Act’s definition of  
“invention.”  
[36] 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 that it would  
have been impossible for the Skilled Person to 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 would be in terms of stability, solubility, permeability and  
bioavailability and adverse effects; none of this would be known without conducting doing  
empirical research.  
[37] 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. 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. The work done by SSCI  
entailed a different type of screening, known as polymorph or crystal screening. Pfizer and Teva  
Page: 15  
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).  
[38] Wyeth not only created the Form I ODV succinate salt, but went further and discovered  
and created the new crystalline Form I ODV succinate claimed in Claims 8 and 9 of the 668  
Patent. Wyeth however did not know that the crystal it created ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| SSCI found another three crystalline and one  
amorphous forms of ODV succinate in addition to crystalline Form I ODV succinate relied upon  
by Pfizer in Claims 8 and 9 of the 668 Patent.  
[39] ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| 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.  
4.  
Invention story in more detail: the evidence of Pfizer’s Dr. Shah  
[40] Pfizer’s Dr. Shah, a pharmaceutical engineer, was the lead investigator involved in  
Wyeth’s development of ODV for clinical research and commercialization between 1999 and  
2004. Dr. Shah’s evidence was that at the outset of the course of Wyeth’s experimentation,  
Wyeth’s Discovery Group considered that ODV might be a successful drug candidate for several  
reasons. ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
 
Page: 16  
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was thought that by administering the metabolite ODV directly one could have a faster and more  
potent effect.  
[41] 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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[42] Wyeth was also interested in improving patient compliance, that is, improving the  
chances of patients actually taking the medication as prescribed, and potential to reduce 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.  
[43] Wyeth’s invention story had several components in addition to this background  
knowledge.  
Page: 17  
[44] Initially, Wyeth worked with ODV fumarate, a known salt form of ODV, but without  
success.  
[45] Wyeth also attempted to make a pro-drug of ODV, again without success.  
[46] In addition, and previously, Wyeth had worked with a number of other salt forms of  
ODV, but without success.  
[47] 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. 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 the 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.  
[48] 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.  
[49] 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  
Page: 18  
performed additional studies to develop sustained release formulations of Form I ODV succinate.  
The following outlines these steps in more detail.  
5.  
Experimentation with ODV fumarate  
[50] Pre-clinical work on ODV by Wyeth’s 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; as Teva notes, ODV fumarate was disclosed as Example 26  
of US 186 as a crystalline salt.  
[51] However, ODV fumarate had problems with bioavailability. ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
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[52] Teva disputes Pfizer’s assertion that ODV fumarate was unsuitable because ||||||||||||||||  
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[53] This evidence indicates and I accept that oral bioavailability of ODV fumarate was  
relatively poor compared to ODV fumarate ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
|||||||||||||||||||||| The problem with the ODV fumarate’s bioavailability was considered by Wyeth as  
“likely due to low solubility and/or permeability” of ODV fumarate. ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
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[54] ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
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Page: 20  
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| , 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 from its acid when it ceased to  
be a salt form in the GI tract, the same dissociation could obtain with other salts. Therefore if the  
dissociated drug ODV did not do well in terms of bioavailability when orally dosed as ODV  
fumarate, it was unclear why another salt form of ODV might behave better once dissociated  
from ODV itself:  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
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||||||||||||||  
Affidavit of Dr. Shah, para 22  
[55] ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||  
6.  
Attempt to form pro-drug of ODV  
[56] Wyeth 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. Depending on the modifications that are made, the pro-drug may have  
improved solubility, dissolution or absorption over the active molecule.  
 
Page: 21  
[57] ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
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||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
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[58] ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
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|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| That said, I accept as a fact that Wyeth did pursue pro-  
drug development in relation to ODV.  
7.  
Attempt to form an acceptable salt of ODV  
[59] The third option contemplated by Wyeth (after the fumarate salt and pro-drugs) to  
improve ODV’s 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 insoluble in water which I accept leads to absorption issues; therefore the ODV  
free base was not pursued.  
[60] I also accept that it was known, as indeed was 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.  
 
Page: 22  
[61] ODV is a base. To attempt to make a salt with ODV, it was therefore necessary to  
interact ODV with an acceptable acid.  
[62] ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
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|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| 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.  
[63] ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
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||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
[64] |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| , Dr. Shah  
proceeded to investigate other salt forms of ODV. This work began by his consulting  
Dr. Hadfield of Wyeth’s Salt Selection Committee for assistance with preparing and screening  
new salts. ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
Page: 23  
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[65] Dr. Shah and Dr. Hadfield started the salt screening process by preparing the  
|||||||||||||||||||||||||||||||||||||||||||||||| salt of ODV. ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
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[66] However, the hydrochloride salt of ODV displayed unfavorable properties for further  
drug development. ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
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[67] After discarding the |||||||||||||||||||||||||||||||| salt as a candidate, Wyeth continued to prepare 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.  
[68] Dr. Hadfield’s 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) ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
[69] In addition to these counter-ions, Wyeth tested additional salts in June and July of 2001.  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
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(a) ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
(b) ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| ||||||||  
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Page: 25  
[70] In addition, Wyeth also screened other types of salts following August 2000, ||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
[71] Teva notes that ODV succinate was one of the first salts identified after salt screening  
commenced; |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| , as reported in para 68(e) above.  
8.  
Polymorph and crystal screening  
[72] 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.  
[73] ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
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[74] While crystallinity was highly desirable for a drug candidate, Dr. Shah’s 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. 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).  
[75] I therefore accept Dr. Shah’s 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. Shah’s 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.  
9.  
Solubility  
[76] After identifying these crystalline salts, Wyeth next evaluated the solubility of the  
potential drug candidates. The solubility of a drug candidate was important. In order for an oral  
dose of a drug to be absorbed in the GI tract, it had 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.  
 
Page: 27  
[77] However, Wyeth was also 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.  
[78] In this connection, ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
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more soluble in my respectful view, which made it a likely candidate for further drug  
development.  
10.  
The Preparation of ODV Succinate  
[79] Given this, it is not surprising and the evidence I accept is that the crystalline salt form  
Wyeth chose for further evaluation was the succinate salt of ODV. ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
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Page: 28  
solid, Dr. Hadfield attempted to induce it into a crystalline form, using a variety of solvents. ||||||  
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[81] ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
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[82] Dr. Shah’s 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.  
11.  
Permeability and bioavailability testing  
[83] Dr. Shah’s 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 team’s 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.  
[84] |||||||||| permeability tests, ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
|||||||||||||||||||||||||||||||||||||||||| and the in vivo rat perfusion test, were initial keys to determining which salt,  
if any, might support once-a-day dosing.  
 
Page: 30  
12.  
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[85] ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
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[86] ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
13.  
Rat perfusion test  
[87] 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 compound’s absorption in the  
various regions of the human GI tract.  
[88] Dr. Shah’s 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.  
   
Page: 31  
[89] The rat perfusion tests involved injecting a solution of ODV succinate directly into  
clamped off sections of the GI tract of male rats (the duodenum, jejunum, ileum and 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.  
[90] ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
[91] The results of the rat perfusion assay are reported in terms of “Peff” values. Peff value is  
the rate of perfusion (in cm/sec) of the drug across the intestinal wall.  
[92] 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 a “Fa” value (“fraction absorbed”), which is the percentage of the drug  
present reliably predicted to be absorbed in the human GI tract.  
Page: 32  
[93] 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 three regions.  
[94] Importantly given Dr. Shah’s 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).  
[95] 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).  
[96] To Dr. Shah’s knowledge, which I accept, ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| His evidence was  
also that although ODV succinate certainly had higher solubility (which can be one factor that  
Page: 33  
contributes to GI perfusion), ODV fumarate would have been expected to behave similarly to  
ODV succinate. He deposed that ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
[97] Teva’s expert Dr. Fiese, infers that because the fumarate salt went to rat perfusion studies  
it |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| However, Dr. Shah could not  
recall if this was the case; Dr. Shah deposed in his reply affidavit that to his knowledge the  
records are not available. Dr. Shah further deposed in his reply to this inference by Dr. Fiese, that  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| I accept Dr. Shah’s evidence that ODV  
fumarate was a natural reference salt for permeability testing of novel salt forms, which included  
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| the rat perfusion in vivo tests.  
[98] Moreover as deposed Dr. Shah, the purpose of Wyeth’s permeability testing was to try  
and improve upon issues observed with the ODV fumarate. ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
Page: 34  
[99] I am not persuaded by Dr. Fiese’s inference in this respect. With respect, I accept  
Dr. Shah’s explanation for two reasons: he was present at the time and his explanation makes  
sense. I accept the evidence of Dr. Shah over the speculation of Dr. Fiese.  
14.  
Beagle dog testing  
[100] Having observed and documented ODV succinate’s superior solubility together with its  
improved permeability over ODV fumarate in the rat perfusion tests, and the relatively poor  
bioavailability of ODV fumarate 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. Shah’s evidence which I accept, was that “[B]ased  
on its superior solubility and permeability characteristics, we expected that ODV 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.”  
[101] Thus ODV succinate was advanced to in vivo beagle dog tests. However, the fumarate  
salt was not subject to beagle dog testing. Teva criticizes the fact that Wyeth did not test ODV  
fumarate in beagle dogs, but in the circumstances that decision is not objectionable because  
Wyeth had already established that the ODV fumarate had poor bioavailability.  
[102] In the beagle dog testing, Dr. Shah’s evidence, which I accept, was that Wyeth was  
looking for an oral dosage forms 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  
 
Page: 35  
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.  
[103] 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 Wyeth’s Gosport facility in the United Kingdom for analysis. The  
concentrations of ODV present in the blood were determined by accepted methods and a number  
of pharmacokinetic parameters were calculated.  
[104] 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  
Page: 36  
(d) absolute bioavailability-which measures the amount of ODV (as a percentage of the  
dose administered) found in the plasma.  
[105] ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
[106] 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.  
15.  
Human Testing  
[107] With the |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| in vivo testing in rats and beagle dogs showing  
positive results, Wyeth moved to testing with 18 human volunteers. Teva questions the fact that  
these test subjects were not patients suffering from depression. However, I am not persuaded this  
objection has merit because the human tests were not designed to test the efficacy of the ODV  
succinate drug in humans, but instead to assess bioavailability and side effects. It was also  
already known that ODV as the metabolite of venlafaxine, commercialized previously and sold  
as EFFEXOR and EFFEXOR XR, was useful in treating depression.  
 
Page: 37  
[108] Wyeth’s 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 Wyeth’s already successfully commercialized sustained release venlafaxine product  
EFFEXOR XR.  
[109] As in Wyeth’s 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 IR and SR 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). ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
[110] The results of the human studies are summarized ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
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.  
[111] 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,  
Page: 38  
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 considered 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.  
[112] 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.  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
[113] 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.  
[114] 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 IR 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  
Page: 39  
on page 53 of the 668 Patent. I am unable to accept Teva’s argument that this concentration is  
arbitrary.  
[115] 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 release versions of ODV succinate when  
in fact there was 1 report for each: this error is not material to the improvement in side effects of  
the sustained version over the intermediate release version.  
16.  
Solid state forms: crystallinity, amorphous solids, polymorphs  
[116] Dr. Shah’s evidence which again I accept was that one criterion for a viable drug form  
was a candidate 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 “amorphous” solids) have molecules that are  
randomly arranged. Crystalline solids were preferable for pharmaceutical drug form  
development because they were typically more stable than amorphous solids.  
 
Page: 40  
[117] 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. Shah and his 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.  
17.  
Polymorph screening and subcontracting polymorph screening to SSCI  
[118] As outlined above, when conducting preliminary screening of ODV succinate for  
crystallinity, Dr. Shah and Wyeth’s Dr. Hadfield created a stable and soluble crystalline  
monohydrate form. However, in order to ultimately develop the compound as a drug, Dr. Shah’s  
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.  
[119] I accept Dr. Shah’s 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  
 
Page: 41  
expected to form. Dr. Shah added that this process is labour intensive and often involves many  
individual experiments, and that ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||  
[120] ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| 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.  
[121] 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) ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
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[122] ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
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|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| I will consider  
these arguments as part of the obvious to try analysis later in these reasons.  
[123] 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 and given to SSCI for its work.  
[124] |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| 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  
properties of ODV succinate, made Form I ODV succinate a very attractive candidate for  
development as a drug. I now turn to SSCI’S involvement.  
,
18.  
Dr. Aeri Park at SSCI  
[125] The person managing the team of scientists conducting SSCI’s 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  
 
Page: 43  
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 SSCI’s laboratory. Her involvement with the ODV succinate project began in  
2001, when Wyeth retained SSCI to conduct a complete polymorph screen of ODV succinate.  
[126] I accept Dr. Park’s 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 the 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.  
[127] ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
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[128] ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
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|||||||||||||||||||||||||||||||||||||||||||||||| Dr. Park deposed, and I accept, that SSCI’s 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.  
[129] Dr. Park’s evidence based on her experience 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  
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  
Page: 45  
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.]  
[130] Dr. Park deposed that:  
Generating Solid Samples  
31.  
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.  
32.  
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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33.  
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.]  
[131] Dr. Park detailed the process SSCI followed in identifying and creating new crystal and  
amorphous forms in her affidavit, which I accept as outlined below:  
Characterization of Initial Solid Samples  
39.  
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||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
43.  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
44.  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
45.  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||  
46.  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| |  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
Page: 48  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||  
47.  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
48.  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
Other Techniques for Analysis and Characterization  
49.  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
50.  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||  
[Emphasis added.]  
[132] ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
Page: 49  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||  
19.  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
[133] ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
20.  
Melting points and differential scanning calorimetry (DSC)  
[134] ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||, 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  
   
Page: 50  
Form “A” was determined to be about 131 °C (endothermic maximum) and the melting point of  
Form “B” was 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 “A” and Form “B”‘. This  
was consistent with the TGA data, where the loss of water did not occur past 100 °C. Hydrates  
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.  
[135] Therefore, the DSC |||||||||||||||||||| data indicated that Forms “A” and “B” are very stable  
hydrates. ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||  
21.  
Further temperature studies and amorphous form  
[136] ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| 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. ||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
 
Page: 51  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||  
[137] During these studies they also identified an amorphous (non-crystalline) form of ODV  
succinate ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
22.  
Hygroscopicity testing (a test relevant to drug statbility)  
[138] ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
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23.  
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[139] ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
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24.  
|||||||||||||||||||||||||||||||||||||| (Crystal Form “C”)  
[140] ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
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)
   
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||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
[141] SSCI thereby identified crystal Forms “A”, “B” and “C”, and then identified crystal form  
“D” through ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
25.  
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| (Crystal Form “D”)  
[142] ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
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||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
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||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
[143] ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
[144] In the result, SSCI identified four polymorph forms of ODV succinate, namely Forms  
“A”, “B”, “C” and “D”. Of these Form “A” was discovered by Wyeth; Wyeth provided Form  
“A” to SSCI. Therefore, SSCI succeeded in identifying three new crystalline forms of ODV  
succinate, plus one new amorphous form. In all, five forms of ODV succinate were identified by  
SSCI, four for the first time.  
[145] ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
Page: 55  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||  
[146] In essence, while Wyeth’s Dr. Hadfield had identified ODV succinate as a salt and had  
also identified a crystal form, SSCI after thoroughly exploring the field, had determined there  
were three other crystalline forms of ODV succinate plus one new amorphous form. ||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||  
26.  
Work on other salt candidates and screens  
[147] Notwithstanding Wyeth and SSCI had made a new composition of matter namely Form I  
ODV succinate in a crystalline form, Dr. Shah’s evidence, which I accept, was that ||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
[148] ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
 
Page: 56  
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V.  
Issues  
[150] As noted previously, while Teva alleged non-infringement and anticipation in its NOA, it  
subsequently withdrew these issues. Mid-hearing Teva also withdrew its allegation that the  
668 Patent was obtained contrary to s 53 of the Patent Act by “material” “untrue” allegations in  
the 668 Patent [henceforth, misleading statements].  
[151] Therefore, the only issues remaining are obviousness and lack of utility, giving rise to the  
following two issues:  
1. Whether Pfizer has discharged its burden to establish on a balance of probabilities  
that Teva’s allegation of obviousness is not justified.  
 
Page: 57  
2. Whether Pfizer has discharged its burden to establish on a balance of probabilities  
that Teva’s allegation of lack of utility is not justified.  
VI.  
Statutory provisions and burden of proof  
[152] Pursuant to s 2 of the Patent Act, to be patented, an invention must be “useful.” Further, a  
new and useful “composition of matter” such 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 l’un  
process, machine, manufacture d’eux, présentant le caractère  
or composition of matter;  
(invention)  
de la nouveauté et de l’utilité.  
(invention)  
[Emphasis added.]  
[Soulignements ajoutés.]  
[153] 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 patent’s 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: 58  
VII. Analysis  
1.  
Relevant Dates  
[154] The relevant dates are mostly agreed upon:  
Filing date in Canada: February 11, 2002, claiming priority to two previous  
applications, dated February 12, 2001 and June 13, 2001;  
Publication date: August 22, 2002;  
Issuance date: May 26, 2009.  
[155] The relevant date for assessing obviousness is February 12, 2001.  
[156] The parties agree that relevant date for assessing utility (whether demonstrated or soundly  
predicted) is the Canadian filing date: February 11, 2002. However, Pfizer denies that  
information that post-dates this date is relevant to Teva’s allegations that the utility requirements  
of the Patent Act have not been met. Teva on the other hand, does not agree that information that  
post-dates the Canadian filing date is irrelevant, taking the position that if a sound prediction has  
subsequently been shown to be wrong, the patent would be invalid for want of utility. Such  
inutility, says Teva, can be proven at a later time. These arguments were made before the  
Supreme Court ruled in Promise Doctrine was not to be followed. Teva also says that a selection  
patent is invalid if further research reveals that a larger number of unselected compounds possess  
the same advantage as that claimed in the selection; I do not need to consider this dispute  
because I have the 668 Patent is not a selection patent.  
   
Page: 59  
[157] 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.  
[158] This application was commenced on August 24, 2015, therefore the 24 month stay  
imposed by the Regulations will expire on August 24, 2017.  
2.  
Claims Construction  
[159] 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. 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  
 
Page: 60  
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.  
[160] That said, there is no substantial dispute between the parties as to what is covered by the  
relevant claims. For completeness I will set out the claims in issue and their construction as  
advanced by the parties as identified in the following agreed Claims Chart. Note that while more  
are outlined below, only Claims 1, 8, 9, 33, 43 and 44 are asserted by Pfizer; the others are  
included for context:  
Claim No. Depends  
From  
Claim Language Pfizer’s Position Teva’s Position  
on Construction on Construction  
(BLANK)  
1.  
None  
A compound  
which is O-  
desmethyl-  
venlafaxine  
succinate or a  
mixed salt  
thereof.  
Not in issue.  
Covers ODV  
succinate, or  
alternatively, a  
mixed ODV  
succinate salt, in  
any form.  
(BLANK)  
2.  
Claim 1.  
A compound  
according to  
claim 1 wherein  
Not in issue.  
Covers ODV  
Page: 61  
Claim No. Depends  
From  
Claim Language Pfizer’s Position Teva’s Position  
on Construction on Construction  
the ratio of O-  
desmethyl-  
venlafaxine to  
succinic acid is  
1:1.  
mono succinate  
in any form.  
(BLANK)  
4.  
Claim 1.  
A compound  
according to  
claim 1 which is a  
hydrate of O-  
desmethyl-  
Not in issue.  
Covers any  
hydrated form  
(i.e., a form in  
which water is  
present in the  
crystal lattice) of  
ODV succinate.  
venlafaxine  
succinate.  
(BLANK)  
5.  
Claim 1.  
A compound  
according to  
claim 1 which is  
O-desmethyl-  
venlafaxine  
Not in issue.  
Covers any  
monohydrated  
form of ODV  
succinate (i.e.,  
wherein there is  
one molecule of  
water present in  
the crystal lattice  
for every  
succinate  
monohydrate.  
molecule of ODV  
succinate).  
(blank)  
6.  
Claims 1, 2, 4 A compound  
Not in issue.  
or 5.  
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  
5, covers any  
crystalline form  
of ODV  
succinate  
monohydrate.  
Page: 62  
Claim No. Depends  
From  
Claim Language Pfizer’s Position Teva’s Position  
on Construction on Construction  
(BLANK)  
8.  
Claim 6,  
A compound  
Covers Form I  
which in turns according to  
ODV (mono)  
succinate  
depend from  
claims 1, 2, 4  
or 5.  
claim 6 which  
exhibits an X-ray monohydrate  
powder (i.e., the  
diffraction pattern crystalline form  
having  
of ODV  
characteristic  
peaks expressed  
in degrees 2ϴ (±  
0.2⁰ 2ϴ) at 10.20,  
14.91, 20.56,  
succinate, which  
exhibits the  
characteristic  
XRPD peaks of  
Figure 1.)  
22.136, 23, 71,  
24.60, and 25.79.  
(BLANK)  
9.  
Claim 6,  
which in turns according to  
A compound  
Covers Form I  
ODV (mono)  
depend from  
claims 1, 2, 4  
or 5.  
claim 6 having an succinate  
endotherm at  
monohydrate  
(i.e., the  
about 131⁰C.  
crystalline form  
of ODV  
succinate, which  
exhibits a  
characteristic  
endotherm at  
about 131⁰C.  
(BLANK)  
33.  
Any one of the Use of an  
claims 1 to 20. effective amount  
of O-desmethyl-  
As it depends on  
claim 8 or 9, use  
of Form I ODV  
succinate for the  
treatment of  
venlafaxine  
succinate or a  
mixed salt thereof depression.  
as claimed in any  
one claims 1 to 20  
for the treatment  
of depression.  
As it depends on  
claims 8 or 9, use  
of therapeutically  
effective amount  
43.  
Any one of the Use of  
claims 1 to 20. therapeutically  
effective amount  
As it depends on  
claim 8 or 9, use  
of a sustained  
release oral  
of sustained  
Page: 63  
Claim No. Depends  
From  
Claim Language Pfizer’s Position Teva’s Position  
on Construction on Construction  
release oral  
dosage form  
of sustained  
dosage form  
comprising O-  
desmethyl;-  
venlafaxine  
succinate or a  
comprising Form release oral  
I ODV succinate dosage form  
to induce an  
comprising Form  
average blood  
plasma level of  
I ODV succinate  
to induce a blood  
plasma level of  
no more than 225  
mixed salt thereof no more than  
as claimed in any 225ng/ml to  
one of claims 1 to lower the overall ng/ml to lower  
20 prepared in a  
dosage to induce  
a blood plasma  
level no more  
incidence of the  
specified side  
effects as  
the incidence of  
the specified  
effects as  
compared to oral compared to oral  
than 225 ng/ml to administration of administration of  
lower the  
incidence of  
ODV succinate  
not so  
ODV succinate  
not so  
nausea, vomiting, formulated.  
diarrhea,  
formulated.  
abdominal pain,  
headache, vaso-  
vagal malaise, or  
trismus resulting  
from the oral  
administration of  
O-desmethyl-  
venlafaxine  
succinate.  
A sustained  
released  
formulation  
comprising O-  
desmethyl-  
44.  
None.  
A sustained  
release  
A sustained  
release  
formulation  
comprising O-  
desmethyl-  
venlafaxine  
succinate and a  
pharmaceutically form, including  
acceptable carrier Form I ODV  
or excipient,  
wherein the  
sustained release  
formulation  
provides peak  
serum levels of up  
formulation  
comprising O-  
desmethyl-  
venlafaxine  
succinate (in any  
venlafaxine  
succinate (in any  
form, including  
Form I OCD  
succinate) which  
provides peak  
serum levels of  
up to 225 ng/ml.  
succinate) which  
provides average  
peak serum  
levels up to 225  
ng/ml.  
Page: 64  
Claim No. Depends  
From  
Claim Language Pfizer’s Position Teva’s Position  
on Construction on Construction  
to 225ng/ml.  
3.  
Obviousness  
A. Introductory comments and summary  
[161] Pursuant to s 28.3 of the Patent Act, an invention must not be obvious to a Skilled  
Person:  
Invention must be obvious  
28.3 The subject-matter  
defined by a claim in an  
application for a patent in  
Objet non évident  
28.3 L’objet que définit la  
revendication d’une 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 l’art ou la science  
dont relève l’objet, eu égard à  
toute communication :  
(a) information disclosed more a) qui a été faite, plus d’un an  
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  
l’information à cet égard de  
façon directe ou autrement, de  
manière telle qu’elle 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 qu’elle 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.]  
   
Page: 65  
[162] One of the two central issues in this case is obviousness, and its ancillary doctrine,  
obvious to try. In my respectful view, and the parties agreed, 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 patent before the Court. I have concluded on this  
aspect of the case that viewed through the eyes of the Skilled Person, and on a balance of  
probabilities that the invention claimed in the 668 Patent, including the inventive concepts of  
Claims 8, 9, 33, 43 and 44, were not obvious and were not obvious to try.  
[163] In my view, the new composition of matter being the crystalline Form I ODV succinate,  
was ‘worth a try’. In addition, there were ‘possibilities’ that 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 try’ is not the test for obvious to try.  
[164] On the evidence, I have concluded that Pfizer has established on a balance of  
probabilities that Teva’s allegation of obviousness including obvious to try are not justified.  
B. The obviousness inquiry  
[165] 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] Sanofi.  
 
Page: 66  
[166] For convenience of reference and because of its centrality on this issue, I will set out  
Sanofi in its entirety 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 try” test 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 try” test really only works where it is  
more-or-less self-evident that what is being tested  
ought to work.  
In General Tire, Sachs L.J. said, at p. 497:  
“Obvious” is, 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 “obvious” to “very plain.” I am of the opinion that the  
“obvious to try” test 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.  
Page: 67  
[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 art” and the inventive  
concept of the claim or the claim as construed;  
(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 try” will arise.  
i.  
When Is the “Obvious to Try” Test Appropriate?  
[68] In areas of endeavour where advances are often won by  
experimentation, an “obvious to try” test might be appropriate. In  
such areas, there may be numerous interrelated variables with  
which to experiment. For example, some inventions in the  
Page: 68  
pharmaceutical industry might warrant an “obvious to try” test  
since there may be many chemically similar structures that can  
elicit different biological responses and offer the potential for  
significant therapeutic advances.  
ii.  
“Obvious to Try” Considerations  
[69] If an “obvious to try” test is warranted, the following  
factors should be taken into consideration at the fourth step of the  
obviousness inquiry. As with anticipation, this list is not  
exhaustive. The factors will apply in accordance with the evidence  
in each case.  
1.  
Is it more or less self-evident that what is being tried ought  
to work? Are there a finite number of identified predictable  
solutions known to persons skilled in the art?  
2.  
What is the extent, nature and amount of effort required to  
achieve the invention? Are routine trials carried out or is the  
experimentation prolonged and arduous, such that the trials would  
not be considered routine?  
3.  
Is there a motive provided in the prior art to find the  
solution the patent addresses?  
[70] Another important factor may arise from considering the  
actual course of conduct which culminated in the making of the  
invention. It is true that obviousness is largely concerned with how  
a skilled worker would have acted in the light of the prior art. But  
this is no reason to exclude evidence of the history of the  
invention, particularly where the knowledge of those involved in  
finding the invention is no lower than what would be expected of  
the skilled person.  
[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  
Page: 69  
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 judge’s findings of fact where they are unaffected  
by his rejection of the “obvious to try” test. 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  
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  
Page: 70  
[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.  
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?  
Page: 71  
[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 try” test 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 try” test, which is warranted in  
this case.  
[83] The following factors are therefore relevant at this fourth  
step of the obviousness inquiry:  
(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 salt’s 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 try” test. 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  
Page: 72  
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.  
[88] However, in considering whether it was “obvious to try” to  
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. Badorc’s 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  
Page: 73  
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. Badorc’s 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  
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 salt’s 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.  
Page: 74  
(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.]  
[167] 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.  
[168] 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 try” test 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 try” test  
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 try” test 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.  
Page: 75  
[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.  
[169] According to this 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 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.”  
[170] 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 try’ test really only  
works where it is more-or-less self-evident that what is being tested ought to work.”  
[171] It recapped these parameters in para 66 stating:  
[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.  
Page: 76  
C. Federal Court of Appeal Jurisprudence  
[172] The Federal Court of Appeal has addressed the obvious to try analysis in several cases  
decided after Sanofi.  
[173] 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 “worthwhile” to 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 “worthwhile” to  
pursue (Pfizer Ltd., supra, para. 107, as quoted at para. 42 above).  
As such, a solution may be “worthwhile” to pursue even though it  
is not “obvious to try” or in the words of Rothstein J. even though  
it is not “more or less self-evident” (Sanofi-Synthelabo, supra,  
para. 66). In my view, this approach which is based on the  
possibility that something might work, was expressly rejected by  
the Supreme Court in Sanofi-Synthelabo, at paragraph 66.  
[Emphasis added.]  
[174] In Novartis, after referring to Sanofi, Justice Hughes discusses the Federal Court of  
Appeal’s 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  
 
Page: 77  
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 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 try” test. 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 Court’s decision in Plavix, cited above, is  
that the key factor in its “obvious to try” analysis  
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.  
and at para 81:  
81  
Given that the Trial Judge applied the test  
for obviousness set out in Plavix, and given that he  
applied it to the same material facts as the Supreme  
Court, he ought to have come to the same  
conclusion. His error lay in failing to recognize that  
the unknown nature of the properties of the  
enantiomers of PCR 4099, or of any of the other  
compounds of the ‘875 Patent, was fatal to the  
Page: 78  
“obvious to try” analysis. Put another way, the  
distance between the common general knowledge  
and the inventive concept of the ‘777 Patent could  
not be bridged by routine experimentation since the  
results to be obtained were unknown. On the facts,  
this was confirmed by the fact that the inventors,  
who had more knowledge that the person of  
ordinary skill in the art, attempted to resolve a  
number of other compounds before finally trying  
PCR 4099: see Reasons, at paragraphs 752-759.  
[65] Gauthier JA wrote concurring reasons. At para 137 she  
wrote:  
137  
The Trial Judge believed that the evidence  
before him with respect to the separation of the  
enantiomers was significantly different from the  
evidence before the Supreme Court of Canada in  
Plavix because: i) he found that a line had been  
drawn in the sand at the time the application was  
filed, and that as part of the process of developing a  
racemic drug a sponsor would be motivated to  
separate the enantiomers to get information to pre-  
empt expected new regulatory requirements (See  
Reasons at paragraphs 748-749); and ii) in his  
view, the separation itself did not involve  
substantial difficulties and was routine. 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 paragraph 89).  
[175] In Eli Lilly v Mylan, 2015 FCA 286, per Dawson J.A., the Federal Court of Appeal at  
para 4, declined to agree with the application of an obvious to try test defined as “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 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  
Page: 79  
para 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.”  
[176] Shortly after the hearing in the case at bar, the Federal Court of Appeal released Bristol-  
Myers Squibb Canada Co et al v Teva Canada Limited, 2017 FCA 76 [Atazanavir]. I therefore  
invited the parties to make written submissions on Atazanavir.  
[177] 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 Court’s decision in Sanofi in relation to obviousness was its adoption of  
the “obvious to try” test [para 34].  
[178] At para 38 the Court said that “… the Supreme Court was quick to add that ‘the ‘obvious  
to try’ test must be approached cautiously” because it “is only one factor to assist in the  
obviousness inquiry”: Plavix 1 at para 64.  
[179] The Federal Court of Appeal confirmed that:  
[60] The reasonable conclusion to be drawn from these  
expressions of caution is that the ‘obvious to try’ test 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 FCR 459 at para  
105.  
Page: 80  
[180] In this connection the Federal Court of Appeal in Atanazavir also referred to the test for  
obviousness prior to Sanofi which test had been set out by the Federal Court of Appeal in Beloit  
Canada Ltd v Valmet OY (1986), 64 NR 287, 8 CPR (3d) 289 at 294 (FCA) [Beloit]:  
[61] While the Supreme Court accepted the ‘obvious to try’ test  
as a way of addressing the issue of obviousness, other inquiries  
remain possible, including the Beloit test, subject to the Court’s  
warnings about a rigid ‘acontextual’ application of that test, or of  
any other for that matter.  
[181] 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.  
[182] 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  
claimed” or simply “the invention” are 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  
the patent” or “the invention”: Proctor & Gamble Pharmaceuticals  
Canada Inc. v. Canada (Minister of Health), 2004 FCA 393,  
Page: 81  
[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 concept” was  
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  
concept” to 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.]  
[183] In Atanazavir 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  
concept” is not materially different from “the solution taught by  
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  
Page: 82  
atazanavir free base. Atazanavir’s 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  
[184] With these principles in mind, I proceed with the analysis of obviousness as set out by the  
Supreme Court in Sanofi.  
E.  
Identify the notional “person skilled in the art”  
[185] A patent is addressed to the person of ordinary skill in the art [Skilled Person], who is  
defined in the jurisprudence as being “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), aff’d 2015 FCA 158. In Beloit, the Federal Court of Appeal refers  
to the Skilled Person as an “unimaginative skilled technician”, and see AstraZeneca Canada Inc  
v Apotex Inc, 2014 FC 638 at para 51 (Rennie, J as he then was) (citing Merck & Co v  
Pharmascience Inc, 2010 FC 510 at paras 34-40 (Hughes, J)), aff’d 2015 FCA 158 (per Dawson,  
J.A.).  
[186] In this case, the parties agree that the Skilled Person would be a person or team of people  
who would have at least a bachelor’s degree in chemistry, pharmaceutics or a related field, and  
   
Page: 83  
relevant practical experience in fields such as pharmaceutical chemistry or pre-clinical drug  
development or pharmacokinetics.  
[187] The parties disagree on whether the Skilled Person in addition requires clinical or  
medical expertise: Teva says the Skilled Person requires clinical or medical expertise, which  
Pfizer disputes. On cross-examination, Dr. Lieberman (a clinical psychiatrist and expert tendered  
by Teva) acknowledged that clinical experience was not required to read and understand the  
668 Patent, including the information about clinical trials and side effects. Teva’s expert also  
agreed that a skilled person could expect that a change in formulation could address tolerability  
related side effects or tolerability kinds of side effects. Dr. Lieberman also agreed that someone  
who is a formulator or a pharmacologist, for example could understand that by preparing a  
sustained release formulation, they might be able to reduce certain GI related and other side  
effects. I note in this connection that the 668 Patent does not specify any particular dosage in  
Claim 43 which instead speaks of “use of a therapeutically acceptable amount”; the 668 Patent  
does not make a claim on a 75 mg or 50 mg or 100 mg or any particular amount of the drug. I  
take this to mean that the “therapeutically acceptable amount” of the medicine claimed is to be  
determined by a person with medical expertise dealing with his or her patient. In these  
circumstances, and in my respectful view, the Skilled Person does not require clinical or medical  
expertise.  
F.  
Identify the relevant common general knowledge of the Skilled Person  
[188] The parties disagree as to what constitutes the common general knowledge of the Skilled  
Person.  
 
Page: 84  
[189] There was some agreement on the common general knowledge and state of the art at  
February 12, 2001. The parties agree that general methods and techniques for salt and crystal  
formation and preparation of sustained release dosage forms were known in the art. Additionally,  
the person of ordinary skill would know that ODV had been disclosed and claimed as an active  
metabolite of venlafaxine and as a member of a class of compounds in several patents: ODV was  
disclosed in US186, CA 540 and WO 851.  
[190] It is also agreed that the prior art disclosed ODV both as a free base and a fumarate salt,  
and that other pharmaceutically acceptable salts (including succinate, among at least eleven (11)  
others as set out in US 186 at column 2, ll. 35 et seq.; 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.  
[191] 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  
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.  
[192] 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 Dr. Myerson  
Page: 85  
deposes at para 81 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 common 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 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.”  
[193] 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,  
whether or not a particular salt formation experiment would result in crystals - to say nothing of  
stable 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.  
Page: 86  
[194] The Skilled Person would know generally of the existence of crystalline and polymorph  
screening. As Dr. Park deposed (see para 129 and following above), polymorph screening was  
not rote work, was difficult and in her experience which was considerable, 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 has 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.  
[195] 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  
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 at paras 129 and  
following of these Reasons. I appreciate that Dr. Park is a named inventor on the 668 Patent, but  
this did not detract from her evidence.  
Page: 87  
[196] Dr. Myerson deposed:  
Choosing an Appropriate Salt  
54. 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.  
55.  
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).  
56.  
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.  
57.  
The salt selection and formation process is highly  
unpredictable. Indeed, one cannot predict prior to actually  
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.  
58.  
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.  
59.  
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  
Page: 88  
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  
60.  
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.  
61.  
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.  
62.  
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  
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.  
63.  
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  
Page: 89  
held together in the crystal form by weak attractive van der Waals  
forces.  
64.  
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.  
65.  
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).  
66.  
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  
“seed” solutions 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.  
Polymorphism  
67.  
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).  
68.  
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  
Page: 90  
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.  
69.  
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  
71.  
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.  
72.  
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  
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.  
73.  
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.  
74.  
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.  
Page: 91  
75.  
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.  
76.  
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  
77.  
Changes in a compound’s solid state form can result in  
significant differences in its chemical and physical characteristics.  
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 compound’s crystal form is extremely important in the  
pharmaceutical industry.  
78.  
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  
Page: 92  
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.  
79.  
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  
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.  
80.  
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 “standard” method 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.  
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: 93  
82.  
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.  
83.  
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.  
84.  
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 ‘all’ of 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.]  
Page: 94  
[197] Teva argues that the common general knowledge of the Skilled Person had additional  
elements. A salt form is often preferable to a free base for reasons including crystallinity,  
solubility, hygroscopicity, stability, and process profile. I accept these submissions, but I also  
accept the concluding words of the paragraph of the 668 Patent relied on by Teva which states:  
“[T]he identification of a salt form that exhibits a suitable combination of properties can be  
difficult.” Teva asserts as part of the common general knowledge a point Pfizer itself stated  
namely that a salt of a compound is generally expected to be more soluble than the free base of  
the same compound.  
[198] Teva further asserts that it was known that such increased solubility “will also improve  
bioavailability” in circumstances where solubility is poor or rate limiting [my emphasis].  
However, I prefer to accept the evidence Teva obtained in cross-examination of Pfizer’s Dr. Polli  
to the effect that what was known was merely that in “some circumstances improving solubility  
could increase bioavailability” [my emphasis] where dissolution is rate limiting.  
[199] Teva says that salt selection strategies and procedures were well known, that regulatory  
authorities required testing for stability and polymorphism, and a simple preliminary study will  
normally show the presence of a stable hydrate. I prefer the evidence of Dr. Jamali which was  
that only properties, such as melting point, stability, and polymorphism had to be tested to be  
determined. Teva overlooks the fact that research and empirical study was also known to be  
required as I have found above; in my view the Skilled Person would know that a research  
program driven by as yet undiscovered empirical data would be necessary if indeed anything of  
merit in this connection might even be found.  
Page: 95  
[200] I agree that salt selection was a procedure known in general terms at the time.  
[201] In terms of regulatory authorities and their requirement for testing, this again is more  
complex that asserted by Teva. It was detailed by Pfizer’s Dr. Myerson in cross-examination by  
Teva, and relied on by Teva, whose evidence I accept in this respect. Dr. Myerson testified that  
FDA guidance “actually required a detailed polymorphism study be done at conditions related to  
the final isolation step of the API. There is no FDA requirement that you do an extensive  
polymorph screen to try to find every possible form. What they’re really interested in is what  
forms might exist at the types of conditions you’re using in your final isolation and are you  
aware of them and can you control your process. And then secondarily, any forms that you’ve  
identified, were they stable on and that in many cases regulatory authorities required testing for  
stability and polymorphism before a drug could be put on the market.” [Emphasis added.]  
[202] Teva says further that the skilled person would attempt to identify the most stable form of  
a compound; I agree but accept what Dr. Jamali added in cross-examination, namely that for  
various reasons drug developers eliminate hydrated forms or solvated forms. And so they would  
pick the most stable non-solvated form.  
[203] Teva then asserts that stability testing, I would call them studies and research, involves  
testing for stability and hygroscopicity (water uptake). I agree, noting that there are different  
ways to study the matter of hygroscopicity as Dr. Chyall testified on cross-examination.  
Page: 96  
[204] Teva further asserts that hydrated forms are often preferred because they are generally  
less likely to be hygroscopic, and therefore may be more stable, which I accept. I accept that  
hydrates should be identified early on to avoid having to repeat testing.  
[205] But these factors simply confirm possibilities for research.  
[206] 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.  
[207] The facts of the matter were stated in Dr. Myerson’s conclusion which bears repeating:  
82.  
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.  
Page: 97  
83.  
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 [sic].  
84.  
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 ‘all’ of them.  
This statement from 1993 remains true, even today. Other  
references contemporary to the 668 Patent similarly highlight the  
unpredictability of developing polymorphs.  
G. Identify the inventive concept of the claim in question or if that cannot readily be  
done, construe it  
[208] Identifying the inventive concept is the next step in the obviousness analysis outlined by  
the Supreme Court in Sanofi. The Federal Court of Appeal in Atanazavir held that the “inventive  
step” is the same as “the solution taught by the patent.” In this connection, having regard to the  
Federal Court of Appeal’s comments concerning Beloit, and the decision of the Supreme Court  
in Sanofi, in my respectful view “what is claimed in the patent” and “the invention” are  
synonymous with “inventive step” and “the solution taught by the patent.”  
 
Page: 98  
[209] This second point, the solution taught by the patent, also known as the inventive concept  
is to be assessed in respect of each claim at issue: Sanofi at para 67. I accept that different claims  
may have different inventive concepts, and as Teva’s expert Dr. Fiese testified, a crystal form  
claim may have a different inventive concept than a salt form claim. Dr. Fiese in cross-  
examination agreed that: “crystalline forms can have inventive concepts that are separate from  
the inventive concept of the salt.” See also: 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.”  
i.  
Claims 8 and 9  
[210] Both of Claims 8 and 9 cover Form I ODV (mono) succinate monohydrate, that is, the  
crystalline form of 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 131⁰C. 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 properties are not the inventive concept, nor are they  
the solution taught by the 688 Patent.  
 
Page: 99  
[211] In my respectful view, the solution taught by these two claims, 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.  
[212] In its affidavit material Teva advances an over-arching inventive concept that applies to  
all the relevant 668 Patent’s claims. Teva’s Dr. Fiese said: “the skilled person would construe the  
inventive concept of the 668 Patent (including all of Claims 1-2, 4-9, 20-21, 23-33, and 43-44),  
as 0-desmethyl-venlafaxine (“ODV”) succinate and its improved physicochemical and  
pharmacokinetic properties, when compared with other forms of ODV.” Teva’s Dr. Jamali  
deposed that Claims 1, 43 and 44 had the same inventive concept. Dr. Lieberman said the  
inventive concept was the same for all the claims, namely that: “… ODV succinate, having  
superior chemical and pharmacokinetic properties compared to other ODV salts and free base.”  
[213] However, Dr. Fiese in cross-examination agreed not only that “crystalline forms can have  
inventive concepts that are separate from the inventive concept of the salt”, but later in his  
affidavit deposed “[C]laim 33 claims the use of ODV succinate for the treatment of depression”,  
and that “[C]laims 43 and 44 are directed to the use of sustained release dosage forms or  
formulations of ODV succinate to provide a specified blood plasma or serum level of no more  
than 225 ng/ml.” On the claims at issue now, 8 and 9, Dr. Fiese agreed in cross-examination with  
Pfizer’s counsel that “insofar as Claims 4 to 9 cover various solid state forms of ODV succinate,  
you recognize that they could have additional inventive concepts associated with them?”  
Page: 100  
[214] No doubt all five claims in issue relate to Claim 1, which is not asserted; Claim 1 is to the  
salt form of ODV succinate (“[A] compound which is O-desmethyl-venlafaxine succinate or a  
mixed salt thereof.”  
[215] However, given this evidence particularly the evidence of Teva’s Dr. Fiese on cross-  
examination, I do not agree that there is an over-arching inventive concept or solution taught by  
the invention applicable to all five claims in issue.  
ii.  
Claim 33  
[216] 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 monohydrate that is, to  
the use of an effective amount of the crystalline form of ODV succinate for the treatment of  
depression.  
[217] I am unable to agree that the ‘overarching’ claim as alleged by Teva’s witnesses applies  
to Claim 33 any more than such an overarching claim might apply to Claims 8 and 9. Such an  
interpretation is not consistent with the evidence, nor with how I construe Claim 33 which is  
written clearly. I see no reason to depart from its plain meaning modified only to acknowledge  
that its inventive concept, or what the 668 Patent teaches in this respect, must be considered  
within the context of my findings with respect to Claims 8 and 9 on which it depends.  
 
Page: 101  
[218] 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.  
iii.  
Claim 43  
[219] 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.”  
[220] As noted there is no substantial disagreement on the construction of Claim 43. In addition  
I have found there is no overarching claim which finding applies to Claims 43 and 44.  
[221] The inventive concept of Claims 43 and 44 is a sustained release dosage form comprising  
the new 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), and therefore reduces the incidence of certain side effects that would otherwise  
result from oral administration of ODV succinate.  
 
Page: 102  
iv.  
Claim 44  
[222] 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.”  
[223] The parties agree on the construction of Claim 44, as follows:  
Claim 44 Pfizer construction  
Claim 44 Teva construction  
A sustained release formulation  
A sustained released formulation  
comprising O-desmethyl-venlafaxine  
comprising O-desmethyl-venlafaxine  
succinate (in any form, including Form I succinate (in any form, including Form  
ODV succinate) which provides average  
peak serum levels up to 225 ng/ml.  
I OCD succinate) which provides peak  
serum levels of up to 225 ng/ml.  
[224] 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.  
[225] Taken together, the evidence of Pfizer’s Dr. Polli, which I accept, is that 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 that Claim 43 references lowering the  
 
Page: 103  
incidence of adverse side effects while Claim 44 does not; both refer to a peak blood plasma  
level of less than 225 ng/ml.  
H. 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  
[226] I will take this stage of the analysis on a claim by claim basis.  
i.  
Claims 8 and 9  
[227] In my respectful view, and as the experts agree, it would not have been possible at the  
relevant time for a Skilled Person to predict whether ODV succinate salt would form as a solid,  
whether that solid would be crystalline, or what the properties of any 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 art.  
[228] 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.  
[229] 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.  
   
Page: 104  
ii.  
Claim 33  
[230] 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.  
[231] Teva says that Claim 33 discloses no further inventive step over Claims 8 and 9. I agree  
with Pfizer that the Skilled Person would know that ODV as the metabolite of venlafaxine was  
useful in the treatment of depression. However, the prior art also taught that every new solid  
form had its own set of unknown, unpredicted and unpredictable properties.  
[232] 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.  
[233] In addition, and in my view for the same reasons that Form I was not more or less self-  
evident, neither was its use to treat depression.  
[234] 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: 105  
iii.  
Claim 43 and 44  
[235] In terms of Claims 43 and 44, both depend on Claims 8 and 9 i.e., the crystalline Form I  
ODV succinate. To recall, the inventive concept of Claims 43 and 44 is a sustained release  
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).  
[236] 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, but Claim 44 does not refer to side effects.  
[237] 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 the non-sustained release  
administration. With respect, I agree.  
[238] I have found that neither ODV succinate nor any of its forms or properties were known,  
predicted or predictable. Therefore 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. As noted in Claim 33, the prior art taught and the Skilled Person knew that every new  
solid form had its own set of unknown, unpredicted and unpredictable properties.  
 
Page: 106  
[239] 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.  
[240] Teva notes that 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 administration, and I agree. But 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 SR formulation. Nor was it obvious or predicted or predictable that ODV succinate Form I  
would have the appropriate 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 SR formulation of ODV succinate would result  
in blood plasma levels below 225 ng/ml which maintaining therapeutic concentrations as per  
both Claims 43 and 44.  
[241] Teva also says the 225 ng/ml ratio is arbitrary, which argument I rejected above at  
para 114. The evidence is that specific Cmax threshold was derived ||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
Page: 107  
Viewed without any knowledge of the alleged invention as claimed, do those  
I.  
differences constitute steps which would have been obvious to the person skilled in  
the art or do they require any degree of invention?  
i.  
Apply the definition of obvious before Sanofi  
[242] At this point in the analysis, in light of Atanzavir and instead of moving next to an  
‘obvious to try’ analysis, I will apply the test for obviousness set out by the Federal Court of  
Appeal in Beloit.  
[243] 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.  
[244] I appreciate Teva’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. In the end, I prefer the evidence of Dr.  
Myerson on the common general knowledge regarding Claims 8 and 9. Dr. Myerson was a  
professor of Industrial Pharmacy and Pharmaceutics, and his evidence was credible and  
comprehensive in this connection. I have also accepted the evidence of Dr. Park based on her  
experience in this connection, see para 129 and following of these Reasons, which corroborates  
that of Dr. Myerson. Dr. Myerson deposed:  
   
Page: 108  
57.  
The salt selection and formation process is highly  
unpredictable. Indeed, one cannot predict prior to actually  
attempting to form a salt whether the reaction of a given active  
drug compound with particular acid or base will successfully  
produce a salt or what the properties of that salt will be.  
58.  
Once a salt form is found with particular counterion, that  
salt is another set of experiments conducted over a variety of  
different conditions to determine what, if any, crystalline forms  
exist for that particular salt.  
59.  
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 salt will affect these properties prior to  
successful formation and analysis of the salt and its solid forms.  
Therefore, it is no 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 desirable properties  
that those of the free base or other salt forms of the drug.  
…
67.  
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).  
…
72.  
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  
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.  
Page: 109  
…
76.  
Like the different polymorphs of 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).  
…
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 “standard” method 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.  
[245] Dr. Myerson concluded:  
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.  
82.  
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;  
Page: 110  
(c)  
what its properties would be, including  
whether there were potential polymorphs, solvates  
and hydrates of that crystal form;  
(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.  
83.  
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 a hygroscopicity, solubility, solid state stability,  
chemical stability and crystal shape (among others) can all  
influence the suitability of a solid form.  
84.  
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 ‘all’ of them.  
This statement from 1993 remains true, even today. Other  
references contemporary to the 668 Patent similarly highlight the  
unpredictability of developing polymorphs.  
[246] 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 as just outlined, would not have  
come directly and without difficulty to the solution taught by the patent, namely the novel  
crystalline form of ODV succinate referred to as Form I.  
Page: 111  
[247] In this connection, the experts agree that it would have been impossible at the relevant  
time for a Skilled Person to predict whether the ODV succinate salt would form as a solid,  
whether that solid would be crystalline, or what the properties of a hypothetical crystalline solid  
would be.  
[248] To recall, 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. In my respectful view, 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 identified or predictable result.  
[249] 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, those findings apply equally to Claims  
33, 43 and 44 as outlined above.  
[250] The obviousness inquiry does not end here. At this point, having looked at obviousness as  
set out in Atazanavir and Beloit, the Court must follow the balance of the steps as suggested by  
Sanofi. The Court must now consider the applicability of, and if appropriate, review the matter  
against the ‘obvious to try’ test.  
Page: 112  
ii.  
Consider the doctrine of obvious to try  
[251] 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 try’ will arise.”  
Having said that the Supreme Court asked: “When Is the ‘Obvious to Try’ Test Appropriate?” In  
answer at para 68 it said: “[I]n areas of endeavour where advances are often won by  
experimentation, an “obvious to try” test might be appropriate. In such areas, there may be  
numerous interrelated variables with which to experiment. For example, some inventions in the  
pharmaceutical industry might warrant an “obvious to try” test since there may be many  
chemically similar structures that can elicit different biological responses and offer the potential  
for significant therapeutic advances.”  
[252] This case falls into the “pharmaceutical industry” category; therefore the next step is to  
consider the factors discussed by the Supreme Court in Sanofi, recognizing that they are not  
exhaustive.  
[253] In doing so regard must be had to the Supreme Court’s introductory comments:  
“[H]owever, the ‘obvious to try’ test 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.” These were  
said to be “useful guidance” by the Federal Court of Appeal in Pfizer v Apotex, 2009 FCA 8 at  
para 26.  
 
Page: 113  
[254] These Reasons will consider the obvious to try analysis first without reference to this  
guidance, and then come back to them to determine what if any difference they make to the  
analysis; in the manner proposed it will be easier to determine the impact of this guidance on the  
Court’s conclusions.  
[255] After establishing this guidance in Sanofi, the Supreme Court set out factors that should  
be considered:  
[69] If an “obvious to try” test is warranted, the following  
factors should be taken into consideration at the fourth step of the  
obviousness inquiry. As with anticipation, this list is not  
exhaustive. The factors will apply in accordance with the evidence  
in each case.  
1.  
Is it more or less self-evident that what is  
being tried ought to work? Are there a finite number  
of identified predictable solutions known to persons  
skilled in the art?  
2.  
What is the extent, nature and amount of  
effort required to achieve the invention? Are routine  
trials carried out or is the experimentation  
prolonged and arduous, such that the trials would  
not be considered routine?  
3.  
Is there a motive provided in the prior art to  
find the solution the patent addresses?  
[70] Another important factor may arise from considering the  
actual course of conduct which culminated in the making of the  
invention. It is true that obviousness is largely concerned with how  
a skilled worker would have acted in the light of the prior art. But  
this is no reason to exclude evidence of the history of the  
invention, particularly where the knowledge of those involved in  
finding the invention is no lower than what would be expected of  
the skilled person.  
[256] I will deal with each of these considerations.  
Page: 114  
J.  
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?  
[257] The parties disagree. Both parties cited cases where, on the accepted evidence in a  
particular case, courts came to conclusions on obvious to try one way or the other. While of  
relevance, each case in this connection has been decided on facts particular to it, and having  
regard to the submissions of the experts and counsel. None of the cases say that all salt screens  
are obvious to try, or are 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 this is a question of applying the law of obvious to  
try to the evidence before the Court.  
[258] 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  
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.  
[259] This summary is borne out in the extracts from the affidavit of Dr. Myerson referred at  
paras 196, 244 and 245. This evidence at least insofar as polymorph and crystal screening is  
concerned is corroborated by Dr. Park’s experience as set out at para 129 and following of these  
reasons. Dr. Myerson concluded with respect to the crystallization and polymorph screening:  
82.  
Overall, given a particular compound, a person skilled in  
the art in the early 2000s would not be able to predict:  
 
Page: 115  
(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.  
83.  
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.  
84.  
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 ‘all’ of them.  
[260] Pfizer’s summary of what the Skilled Person would know is to my mind confirmed by the  
cross-examination of Teva’s expert Dr. Fiese. Relevant extracts include:  
420  
Q. Okay. We’ll come back to that. You’d agree with me,  
Dr. Fiese, that you can’t predict in advance whether a particular  
salt of a compound will form a crystalline salt?  
Page: 116  
A. That’s correct.  
421  
Q. You also can’t predict what the other properties of that  
salt might be?  
A. That’s correct.  
Q. You don’t know whether ODV tartrate has a crystalline  
660  
monohydrate form, do you?  
A. No.  
661  
Q. And you don’t know whether ODV maleate has a  
crystalline monohydrate form?  
A. No.  
689  
Q. In your view, a skilled person has an expectation that  
they will find a salt with suitable solubility if they conduct a salt  
screen?  
A. Yes  
690  
Q. But a skilled person is not going to know which salt that  
is going to be in advance?  
A. No, not in advance.  
691  
Q. And they’re not going to know how many salts they’re  
going to need to make before they find it?  
A. That’s correct.  
847  
Q. If we go back to your affidavit, I would like to turn  
paragraph 113. In paragraph 113 you say a skilled person would  
have expected that one or more of the ODV salts identified in the  
U.S. ‘186 and WO 851 patent would be suitable for use in a solid  
oral dosage form?  
A. Yes.  
848  
Q. What the skilled person could not have expected is  
which salt that would be?  
A. That’s correct.  
850  
Q. So we know now that ODV succinate is a suitable salt of  
ODV?  
Page: 117  
A. Yes.  
851  
Q. But a person skilled in the art in February 2001 wouldn’t  
have known that?  
A. They would have known fumarate would work. They  
would have been encouraged to stay in that family but they  
wouldn’t have known specifically if succinate worked.  
861  
Q. And so this statement that the skilled person would  
readily determine that ODV succinate would be one such suitable  
salt, again, that is the statement that you’re making with the benefit  
of hindsight?  
A. You also knew the fumaric was going to work, so the  
prior art would tell you that you want to go in that area.  
862  
Q. Right.  
A. So it’s not an after-the-fact thing; it was more of a prior  
thing.  
863  
Q. Right, but the knowledge that ODV is a suitable salt that  
works is knowledge we have now?  
A. Yes.  
864  
872  
Q. It’s not knowledge a skilled person would have in 2001?  
A. Not before they made it, no.  
Q. In 2001 it would not have been possible to predict how  
many crystalline forms a compound had?  
A. That’s correct.  
873  
Q. Or what they would be?  
A. That’s correct.  
877  
Q. When you say it would be obvious to try to make and  
characterize that form, you’d agree with me a skilled person as of  
2001 doesn’t know that Form I exists, correct?  
A. I think that’s correct.  
878  
Q. So I think what you mean here is a skilled person would  
be motivated to try to generate crystalline solids of ODV  
succinate?  
Page: 118  
A. Yes.  
879  
Q. And they would be motivated to try to identify a  
crystalline solid that was stable at ambient conditions?  
A. Right.  
880  
Q. So what you’re saying is that in doing that they may  
arrive at Form I?  
A. Right.  
881  
Q. But they could not predict in advance that Form I  
existed?  
A. No.  
882  
Q. Or what its properties would be?  
A. No, they couldn’t.  
883  
Q. Or what its characteristics would be, like its XRPD  
pattern?  
A. That’s correct.  
Q. As of 2001 if you had asked a skilled person to describe  
884  
a stable crystalline form of ODV succinate they could not have  
done that?  
A. No. You knew the properties you wanted to have, but  
does succinate have it? No idea.  
885  
Q. Right. And you don 1 t know that there ‘ s going to be a  
particular crystal form with the XRPD pattern set out in Claim 8  
that’s going to satisfy that requirement?  
A. No.  
886  
Q. And I think we had talked about the generation of  
different salts using different conditions, but I ‘m right that  
different conditions can also result in different solid state forms?  
A. Oh yeah.  
887  
Q. So if I vary the conditions of my crystallization  
experiment I can get one solid state form versus another solid state  
form of the same compounds?  
Page: 119  
A. So if I vary the conditions of my crystallization  
experiment I can get one solid state form versus another solid state  
form of the same compounds?  
888  
Q. And these conditions that I would vary would include  
things like solvent?  
A. Yes.  
889  
890  
891  
892  
893  
894  
895  
Q. Temperature?  
A. Yes.  
Q. Prescription method?  
A. Yes.  
Q. Timing?  
A. Timing, yes.  
Q. Humidity?  
A. Probably not.  
Q. Or presence of water?  
A. Presence of water.  
Q. Degree of mixing?  
A. Yes.  
Q. And the form that is going to result from any given  
crystallization experiment is going to depend on those conditions  
that I select?  
A. Correct.  
896  
897  
Q. And that’s not something I can predict in advance?  
A. No.  
Q. Empirical?  
A. Yes.  
Page: 120  
[261] In my respectful view, this evidence of Dr. Fiese contradicts what he deposed in his  
affidavit. In my view this contradictory evidence considerably weakens his evidence. In his  
affidavit, Dr. Fiese deposed:  
114. I do not agree with Dr. Chyall’s assertion (paragraph 44)  
that:  
A skilled person would have no way to predict what  
amount of effort, conditions or experiments would  
be required to reach any salt form of ODV, or that  
any particular salt could be made successfully or  
would have properties that would be suitable for  
formulation.  
115. Similarly, Dr. Myerson states (paragraph 42) that: “It could  
not have been more or less self-evident to a skilled person that any  
particular salt of ODV (including succinate) could be made... “ and  
that “a skilled person could not have predicted that any particular  
salt of ODV (including succinate) would have properties that  
would make it suitable for formulation in advance of actually  
making and testing it.”  
116. This dramatically overstates the uncertainty involved in the  
process by presuming that the skilled person must pick a suitable  
salt before testing any of the salts. In pharmaceutical science, there  
is never a guarantee of success, or a guarantee that things will be  
easy. However, in the case of ODV, it is my opinion that the  
skilled person would be confident that a suitable salt form could be  
identified with a routine salt screen. The skilled person would  
readily determine that ODV succinate would be one such suitable  
salt. Dr. Shah’s affidavit confirms that this was in fact.  
[Emphasis in original.]  
[262] In this connection, I note that Dr. Fiese’s answers to question 863 and 864 support  
Pfizer’s contention that Dr. Fiese’s affidavit evidence relied on impermissible hindsight  
regarding the ODV succinate salt. In the circumstances I accept Dr. Fiese’s testimony on cross-  
examination over that deposed in his affidavit.  
Page: 121  
[263] Based on this evidence I conclude that it was not more or less self-evident to the Skilled  
Person that what is being tried, namely the crystalline Form I ODV succinate, ought to work.  
This is the evidence of Dr. Myerson, and in my view it is confirmed in material ways by  
Dr. Fiese. In summary, I find that the crystal form of Form I ODV succinate was not more or less  
self-evident to the Skilled Person.  
[264] The second part of this question asks whether there are a finite number of “identified  
predictable solutions” known to persons skilled in the art; in my view this was not the case  
because the number of potential experiments was in fact extremely 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 “standard” method 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.  
[Emphasis added.]  
Page: 122  
[265] This fact was confirmed by Dr. Park’s experience who deposed at para 31 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.”  
[266] 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 indeed the possibility of engaging on a research program, in my respectful view on  
the facts of this case there were no identified predictable solutions.  
[267] Teva argues that because salt screens and polymorph tests, among other things, were  
generally known in the prior art, it would be more or less self-evident to the Skilled Person that  
Form I ODV succinate, i.e., what is being tried, ought to work. I disagree. A general knowledge  
of salt screens and what was known of polymorph tests merely provided possibilities for  
conducting research, studies and further experiments which in this case was in the nature of a  
research program. 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.  
[268] 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 arguments like those of Teva here, stated:  
[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  
Page: 123  
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 try” test. That is not the evidence in this case.  
[Emphasis added.]  
[269] 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  
crystallization and polymorph screening it might be possible to identify crystals and polymorphs,  
but the Skilled Person would also know that no such crystal or polymorph forms might be  
possible, and that even 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. In my view these were mere possibilities  
of identifying the ODV succinate salt, or perhaps no salt at all, in a salt screen in first instance,  
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. Again, mere possibilities are  
not sufficient.  
[270] 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. But I disagree with  
the position advanced by Teva that this makes the present invention one that was obvious to try;  
in my view far more than routine experimentation would have been foreseen by the Skilled  
Page: 124  
Person in this case. A general knowledge of salt screens and what was known of crystallization  
and polymorph screening, merely provided possibilities for 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.  
[271] Another fundamental problem with these arguments is that they are contrary to the expert  
evidence of Dr. Myerson and the experience of Dr. Park which I have accepted. That aside, even  
if all of these arguments are accepted as being in the prior art, contrary to my findings, in my  
view they simply set up the very same situation 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.”  
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 try’  
test. That is not the evidence in this case.  
[272] 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 evidence in this case. I am unable to find  
that the uninventive and unimaginative Skilled Person would consider the invention was self-  
evident from the prior art and the common general knowledge.  
Page: 125  
[273] In my respectful view the situation outlined in Sanofi 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.  
[274] However the Skilled Person would also know that no such 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 instance, and a possibility of finding Form I ODV succinate crystalline, or  
perhaps no crystalline form at all, in crystallization and polymorph screening. But mere  
possibilities are not sufficient.  
[275] In my view, this head points against a finding of obvious to try in this case.  
K. 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?  
[276] 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 196, 244 and 245. I also have  
accepted Dr. Park’s experienced-based evidence on crystallization and polymorph screening –  
 
Page: 126  
see above at para 129 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.  
[277] Again with reference 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 is 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, 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. ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
|||||||||||||||||||| The nature of the work seen in this context was uphill.  
[278] 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.  
Page: 127  
[279] 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 ||||||||||||||||||||||||||||||, rats, dogs and humans. While Teva  
points to a 1994 document in which Pfizer personnel characterized salt formation “as a simple,  
almost trivial, means of overcoming some undesirable properties e.g. solubility, stability and  
dosage form manufacturability of the parent drug substance”, in my respectful view the invention  
story considered not in isolated components but as a whole, from the initial pro-drug  
experiments, the salt selection processes, the exploration of the properties of ODV succinate,  
SSCI polymorph and crystallization work leading to the discovery of the new crystal forms  
including Form I ODV succinate, was anything but trivial.  
[280] This factor points away from finding obvious to try.  
L.  
Is there a motive provided in the prior art to find the solution the patent addresses?  
[281] 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.  
 
Page: 128  
[282] 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.  
[283] Pfizer’s position is that beyond a general statement about the possibility 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 the 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.  
[284] 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 pursue” the  
invention claimed. There as here, there is a lack of specific motivation, and I emphasize the  
words “specific motivation”, in the prior art to find the novel crystalline Form I ODV claimed by  
the 668 Patent.  
[285] I note also that Sanofi dealt with a genus patent, where, as the Supreme Court stated,  
“selection might be expected” at para 90, but nonetheless the Court found no motivation in the  
Page: 129  
prior art in that case; neither do I in the case at bar. In this case, which does not involve a genus  
patent [see discussion following], the prior art did not differentiate between the pharmaceutically  
acceptable salts of ODV, or possible crystalline forms.  
[286] In my view, this aspect of the obvious to try test favours Pfizer.  
M. The 668 Patent is not a selection patent  
[287] As just noted, in my respectful view, the 668 Patent is not a selection patent. This was  
another point on which the parties divided. The definition of a selection patent is set out by the  
Supreme Court in Sanofi:  
[1]  
This appeal raises questions relating to the validity of what  
are known as selection patents. In the context of chemical  
compounds, in general terms, a selection patent is one whose  
subject matter (compounds) is a fraction of a larger known class of  
compounds which was the subject matter of a prior patent.  
…
[9]  
The locus classicus describing selection patents is the  
decision of Maugham J. in In re I. G. Farbenindustrie A. G.’s  
Patents (1930), 47 R.P.C. 289 (Ch. D.). At p. 321, he explained  
that in the field of chemical patents (which would of course  
include pharmaceutical compounds), there are often two “sharply  
divided classes.” The first class of patents, which he called  
originating patents, are based on an originating invention, namely,  
the discovery of a new reaction or a new compound. The second  
class comprises patents based on a selection of compounds from  
those described in general terms and claimed in the originating  
patent. Maugham J. cautioned that the selected compounds cannot  
have been made before, or the selection patent “would fail for want  
of novelty.” But if the selected compound is “novel” and  
“possess[es] a special property of an unexpected character”, the  
required “inventive” step would be satisfied (p. 321). At p. 322,  
Maugham J. stated that a selection patent “does not in its nature  
differ from any other patent.”  
 
Page: 130  
…
[11] Although much has been written about selection patents  
since I. G. Farbenindustrie, Maugham J.’s analysis is consistently  
referred to and is well accepted. I find it is a useful starting point  
for the analysis to be conducted in this case.  
[288] The issue of selection patent is not an independent basis to attack a patent; selection  
patents are treated like other patents in accordance with the Patent Act and applicable law. Issues  
arising out of a selection patent are considered in the obvious analysis. It is an error of law to rely  
on the conditions for a valid selection patent as constituting an independent basis upon which to  
attack the validity of a patent: Eli Lilly v Novopharm, 2010 FCA 197 at para 4.  
[289] In the case at bar, Teva relies on the US 186 Patent and WO 851 to describe the first, or  
originating class of compounds disclosed, as discussed in the extract from Sanofi just cited.  
[290] The difficulty with this argument is that while US 186 and WO 851 disclose ODV as a  
free base and a fumarate salt, and refer both the ODV succinate salt and the possibility of other  
salts, nothing in the prior art discloses the crystalline form of ODV succinate known as Form I  
which is the subject of each of the asserted claims 8, 9, 33, 43 and 44. While the salt was  
disclosed, the crystal form was not.  
[291] In my respectful view one cannot have a selection patent unless the compound claimed as  
the selection patent is a compound that was previously claimed, i.e., included within the genus of  
a previous patent. The second invention must be a selection from the prior art genus. The novel  
crystal Form I ODV succinate is a new composition of matter; it is a three-dimensional  
Page: 131  
arrangement of the atoms and molecules of ODV succinate. It was not found in the genus of any  
other patent. Therefore this is not a case of a second invention being selected from the prior art  
genus. Therefore this is not a selection patent.  
[292] No previous patent claimed this crystalline form. Further, the Skilled Persons could not  
have predicted that this new crystalline Form I ODV succinate could or would occur. There is no  
evidence that the crystalline Form I ODV succinate was claimed in a prior patent or disclosed in  
the prior art. Because the crystal Form I ODV succinate is not a narrow class of compound  
covered by a previous genus, or originating patent, the crystal Form I falls outside the very  
nature of a selection patent by its definition: Pfizer v Ranbaxy, 2008 FCA 108 at para 45.  
[293] I agree that the new crystal form claimed is at the heart of the invention of Claims 8  
and 9 of the 668 Patent. Its use to treat depression is covered by Claim 33 which paves the way  
for sustained release oral formulations that could deliver identified therapeutic concentrations of  
ODV to the bloodstream over a prolonged period of time and reduce the overall incidence of  
certain side effects associated with higher peak blood concentrations. It is this formulation that is  
the invention in Claims 43 and 44 of the 668 Patent.  
N. What is the course of conduct followed which culminated in making the invention?  
[294] 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.  
 
Page: 132  
[295] I accept Teva’s submission that the salt form ODV succinate was made as a new  
composition of matter - ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||| However, and while much was made of it and without doubting its  
relevance on this branch of the Sanofi inquiry, the time taken to make a new invention is but a  
single factor. This is particularly the case given the evidence that this particular salt and  
crystalline form was not identified or predicted or predictable. I have noted the evidence, 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.  
[296] ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
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[297] Moreover, the invention story in this case 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  
screen began, including work on the fumarate salt, and the work done developing an ultimately  
unsuccessful pro-drug. 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.  
Page: 133  
[298] ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| But again that was neither  
predictable nor predicted. Moreover, additional testing was needed to determine whether there  
were other forms of ODV succinate, and very importantly, additional experimentation was  
required to determine which if any crystal form of ODV succinate was the most stable, i.e., the  
best candidate for further drug development. The fact that Wyeth also discovered what turned  
out to be the most stable crystal form of Form I ODV succinate and did so before Wyeth engaged  
SSCI does not detract from the fact the salt and crystal experimentation required was much more  
than routine.  
[299] 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.  
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[301] On balance, and in my respectful view, the actual course of conduct in this case entailed  
more than routine experimentation. It was in fact a research program. Significantly, the Skilled  
Person, in my view, would have foreseen it as such. The SSCI research took five months, as an  
example.  
[302] 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 relevant: “137... [H]owever, Rothstein J. made it clear in Sanofi 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 Sanofi at para 89).”  
[303] These circumstances favour Pfizer in the obvious to try analysis.  
i.  
Conclusions on obvious to try regarding Claims 8 and 9  
[304] 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.  
 
Page: 135  
ii.  
Conclusions on obvious to try regarding Claims 33, 43 and 44  
[305] 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.  
O. Consideration of guidance of obvious to try analysis set out in Sanofi  
[306] I have made these findings without specific reference to the guidance set out at the  
commencement of the Supreme Court’s discussion of obvious to try in Sanofi. There, the Court  
stated that the obvious to try doctrine must be “approached cautiously”, that it is “only one factor  
to assist in the obviousness inquiry”, and that obvious to try “not a panacea” at para 64.  
[307] The need to be cautious approach leads me to the same conclusion as just made, as does  
being guided by the warning that obvious to try is not a ‘panacea’.  
[308] I turn to the Supreme Court’s considerations 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]. These guiding principles confirm my finding  
on a balance of probabilities, that Teva’s allegation of obvious to try are not justified.  
[309] In summary, the guidance provided by the Supreme Court with respect to obvious to try  
supports the conclusions drawn.  
   
Page: 136  
P.  
Conclusion on obviousness  
[310] In my respectful view, the Applicant has established on a balance of convenience that  
Teva’s allegation of obviousness is not justified.  
4.  
Utility  
[311] Utility is required for an invention to be patentable: Patent Act at s 2:  
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 l’un  
process, machine, manufacture d’eux, présentant le caractère  
or composition of matter;  
(invention)  
de la nouveauté et de l’utilité.  
(invention)  
[Emphasis added.]  
[Soulignement ajouté.]  
[312] Previously, the discussion of utility would start with 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 and the case at bar. Both parties filed main and  
responding submissions.  
[313] Teva properly conceded that in view of AstraZeneca, “it is clear that the ‘promises’ of the  
668 Patent are no longer ‘the yardstick against which utility is measured’.” Instead, Teva  
   
Page: 137  
submitted that: “it is clear that the mischief of overpromising is addressed instead by reference to  
s 27(3) and s 53 of the Patent Act, and that a disclosure which is not correct and full, or which  
states an unsubstantiated use or operation of the invention, may be found to fail to fulfill the  
requirements of s 27(3).”  
[314] In this connection, I note Teva did not refer to subsection 27(3) in its memorandum of  
fact and law, nor did Teva refer to subsection 27(3) in the outlines of argument filed at the  
hearing. While Teva originally alleged misrepresentation contrary to s 53 of the Patent Act, it  
withdrew that allegation at the hearing.  
[315] Teva submitted argument on two main points arising out of AstraZeneca, obviousness  
and insufficiency:  
Teva’s Notice of Allegation addressed the same factual allegations  
regarding the deficiencies of the data underlying the 668 Patent  
under various headings, including obviousness, utility and  
insufficiency of disclosure. In view of Esomeprazole, the  
deficiencies of the data underlying the 668 Patent are properly  
addressed in relation to obviousness (there is no special advantage)  
and insufficiency (the disclosure of the properties of the salts of  
ODV is not correct and full). The evidence shows that the 668  
Patent is invalid for both obviousness and insufficiency.  
[316] While I agree that Teva’s NOA addressed deficiencies in data underlying the 668 Patent,  
the NOA did so only in the context of its allegation that the 668 Patent is a selection patent,  
identifying this allegations under the combined heading “INSUFFICIENCY / INVALID  
SELECTION.”  
Page: 138  
[317] In terms of obviousness, Teva repeated the arguments it made throughout that the results  
of salt screens have in other cases been found to be obvious “as addressed in detail in Teva’s  
previous submissions”, adding that “[A] scintilla of utility does not render a salt non-  
obviousness: the utility of table salt does not make table salt patentable.” On the evidence in this  
case, however, I have found that the invention of the crystalline Form I ODV succinate was  
neither obvious nor obvious to try.  
[318] With respect to insufficiency, Teva notes that AstraZeneca held, among other things, that  
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).” However, as noted, Teva  
did not refer to subsection 27(3) in its memorandum of fact and law, or for that matter, in any of  
the outlines filed at the hearing.  
[319] Teva noted AstraZeneca’s acceptance that “inventions are like a many-faceted prism:  
multiple claims (sometimes running into the hundreds) covering all facets are allowed in the  
same patent if a ‘single general inventive concept’ links them.”  
[320] Teva argued that the 668 Patent is a selection patent that is primarily based upon the  
properties of the succinate salt of ODV such that the single general inventive concept was ODV  
succinate, the same inventive concept as Claim 1. It argued that the “disclosure of the 668 Patent  
is insufficient, as the advantages stated in the 668 Patent cannot meet the requirements for a valid  
selection patent.” In this respect, Teva relied on Eli Lilly v Novopharm, 2007 FC 596 at where  
Justice Hughes stated:  
Page: 139  
The general jurisprudence as to sufficiency of disclosure must be  
considered in light of the particular requirements respecting  
selection patents [i.e.] that the inventive feature of selection of a  
compound or group of compounds from a larger group must reside  
in the unexpected or surprising attributes of the selected compound  
or groups and that this inventive feature must be clearly set out in  
the specification.  
[321] I have previously found that the 668 Patent is not a selection patent. Therefore, and in my  
respectful view, Teva’s arguments based as they are on the incorrect premise that the 668 Patent  
is a selection patent, are not relevant to the inutility analysis post-AstraZeneca.  
[322] Pfizer in its post-hearing AstraZeneca filing submitted that in Astrazeneca, the Supreme  
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 … even where multiple uses are disclosed or  
described.” Pfizer added:  
2.  
While the 668 Patent may disclose multiple uses relating to  
the 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 Court’s guidance, the utility associated with  
that novel crystal form is solid-state stability. The inventors  
demonstrated the solid-state stability of the crystal form prior to  
the relevant date. This is a complete answer to Teva’s allegation  
that the subject matter of claims 8 and 9 was not “useful” under  
section 2 of the Act.  
3.  
Teva 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, its argument that the Asserted Claims lacked  
utility was based on its allegation that claims 8 and 9 were  
associated with multiple, overarching promises, including promises  
Page: 140  
relating to the comparative properties of the salt and the reduction  
of side effects.  
[323] 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  
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).  
Page: 141  
[324] 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. Only a scintilla of utility is required.  
A. First identify the subject-matter of the invention as claimed in the patent, and second,  
is that subject-matter useful – is it capable of a practical purpose (i.e. an actual result)  
[325] AstraZeneca states at para 53 that “utility will differ based on the subject-matter of the  
invention as identified by claims construction.” 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.  
[326] Therefore the utility analysis will proceed on a claim by claim basis, and having regard to  
the construction given each of the asserted claims in the 668 Patent, namely Claims 8, 9, 33, 43  
and 44. It should be recalled that the parties substantially agreed on the construction of Claims 8,  
9 and 33.  
[327] Claims 8 and 9 - The parties agreed that the subject matter of Claims 8 and 9 is Form I  
ODV succinate. The subject matter of claims 8 and 9 is the novel crystalline form of ODV  
succinate, which is Form I ODV succinate. This answers the subject matter of the invention and  
the first part of the AstraZeneca inquiry.  
 
Page: 142  
B. Is Form I ODV succinate, the subject matter of Claims 8 and 9, useful - is it capable  
of a practical purpose (i.e. an actual result)?  
[328] Pfizer says, and I agree, that by the relevant date it was established that Form I ODV  
succinate was useful as a stable, solid-state form of ODV succinate. In my view, this practical  
usefulness is related to the subject matter of Claims 8 and 9 given the useful and important  
purpose in drug development to identify a solid form of a drug that is stable under relevant  
conditions including manufacture, distribution, and storage until administration to the patient. To  
the same effect was the testimony of Teva’s Dr. Fiese who agreed that stability in terms of  
ambient conditions of relative humidity and temperature made a better candidate for a drug,  
i.e., “it will not change on you.”  
[329] In this connection, I conclude that stability was demonstrated by the facts, which are not  
contested, namely that Form I ODV succinate was shown to be stable at ambient room  
temperature and up to 105⁰C, and physically stable from 5% to 95% relative humidity. ||||||||||||||  
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|||||||||||||||||||||||||| These were the findings of Dr. Park at SSCI which I have accepted: see above at  
paras 136, 138 and 145.  
[330] Pfizer also argued that the practical usefulness of the drug as a stable solid form is alone  
sufficient utility under AstraZeneca in this context. I agree. However, because they were argued  
before me, I will review other alleged utilities.  
 
Page: 143  
[331] Pfizer says that the inventors of the 668 Patent had demonstrated that ODV succinate and  
Form I ODV succinate had additional useful and practical properties namely, improved  
solubility, permeability and bioavailability over previous forms of ODV: ODV free base and  
fumarate. As the following analysis based on my previous findings confirms, I agree.  
[332] The utility of ODV succinate the salt (Claims 1 to 7) was both demonstrated and soundly  
predicted. It was demonstrated by the high and improved solubility and its increased solubility  
across all relevant pH ranges in the GI over ODV fumarate ||||||||||||||||||||||||||||||||||||||||||||, as set out  
previously in these Reasons. It had improved and high permeability as demonstrated by its  
increased permeability across the rat GI tract over ODV fumarate |||||||||||||||||||||||||||||||||||||||||||| as shown  
in the rat perfusion tests and resulting widely accepted predictive Peff and Fa values. Solubility  
was therefore demonstrated and based on a sound line of reasoning.  
[333] ODV succinate also provided improved high bioavailability. Bioavailability is largely a  
function of solubility and permeability; improvements in both solubility and permeability will  
result in an improvement in bioavailability. ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
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||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||  
|||||||||||||||||||||||||||||||||| Predicted human oral bioavailability from the rat perfusion test was higher for  
succinate than for either fumarate ||||||||||||||||||||||||||||  
[334] Moreover, in my view the ODV succinate salt’s utility was also soundly predicted mostly  
for the same reasons, namely it having high, suitable and improved solubility, together with  
Page: 144  
improved permeability. The rat permeability calculations showed that ODV succinate would  
have higher overall bioavailability than fumarate ||||||||||||||||||||||||||, rat perfusion testing and the use of  
Peff and Fa values being well-accepted models of GI permeability.  
[335] I should also note that Teva’s arguments against the utility of Form I ODV succinate was  
based entirely on the Promise Doctrine which has now been rejected; previously, Teva did not  
dispute that Form I ODV succinate had utility outside the Promise Doctrine.  
[336] 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.  
[337] Claim 44, as it depends on Claims 8 or 9, and 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.  
[338] 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).  
Page: 145  
C. Are the subject matters of Claims 33, 43 and 44 useful – are they capable of a  
practical purpose (i.e. an actual result)?  
[339] 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.  
[340] In my view, the inventors demonstrated and, in the alternative, soundly predicted that  
Form I ODV succinate 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 patient’s 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, any utility associated with  
Claim 33 was also demonstrated.  
[341] 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 that ODV was the active metabolite of venlafaxine,  
which was approved and used for the treatment of depression as EFFEXOR and EFFEXOR XR.  
In other words, the anti-depression pharmacological activity of ODV was known. Further, just as  
noted Form I ODV succinate was shown to be capable of getting into the bloodstream at  
 
Page: 146  
therapeutically effective concentrations. 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.  
[342] Claims 43 and 44. - In my view the inventors demonstrated at the relevant time that  
sustained release formulations of ODV succinate (specifically, Form I) that induced the requisite  
blood plasma level led to an overall reduction in side effects as compared with immediate release  
formulations, as explained by Dr. Polli: “…sustained release formulations which resulted in peak  
plasma concentrations of less than 225 ng/mL (the lower end of the range for the immediate  
release formulation) would result in a reduction of these side effects over immediate release  
formulations of ODV succinate.”  
[343] These formulations are intended to release a drug more slowly in order to reduce blood  
concentrations and therefore side effects.  
[344] Pfizer notes that the issue of side effects is irrelevant insofar as Claims 8, 9 and 33 are  
concerned.  
[345] For Claims 43 and 44 in terms of the utility inquiry after AstraZeneca, the issue is  
whether, as AstraZeneca teaches, the subject matter of these claims - which is a sustained release  
formulation of ODV succinate that results in a Cmax of less than 225 ng/mL - is useful. In my  
respectful view, the usefulness of the sustained release formulations in reducing side effects  
Page: 147  
compared to immediate release was demonstrated by the inventors and reported in the 668  
Patent, as just discussed, and confirmed by Dr. Shah and Dr. Polli and as stated in the 668 Patent.  
[346] This usefulness is clearly a practical purpose (i.e. an actual result). Therefore Pfizer has  
met the requirements of the Patent Act’s usefulness requirements as determined in AstraZeneca;  
additional statements in the 668 Patents referring to a reduction of side effects need not be  
considered because they are irrelevant.  
[347] Given the above, I am satisfied on a balance of probabilities that Teva’s allegations of  
inutility are not justified.  
VIII. Conclusion  
[348] Having concluded on a balance of probabilities that Pfizer has established that Teva’s  
allegations of obviousness and lack of utility are not justified, the Applicant Pfizer is entitled to  
an order prohibiting the Minister of Health from issuing a Notice of Compliance in respect of a  
Notice of Allegation sent by Teva Canada Ltd. to Pfizer Canada Inc., previously Wyeth LLC,  
dated July 10, 2015, in respect of Canadian Patent No. 2,436,668 which is issued as part of the  
Judgment herein.  
 
Page: 148  
IX.  
Costs  
[349] Costs shall follow the event and Pfizer shall have its costs against Teva as set out in the  
terms, which the Pfizer and Teva agreed upon in advance of these reasons, and which are  
scheduled to this Judgment.  
X.  
Confidential Reasons  
[350] 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: 149  
JUDGMENT  
THIS COURT’S JUDGMENT is that:  
1.  
2.  
The application is granted.  
The Minister of Health is prohibited from issuing a Notice of Compliance in respect  
of a Notice of Allegation sent by Teva Canada Ltd. to Pfizer Canada Inc., previously  
Wyeth LLC, dated July 10, 2015, in respect of Canadian Patent No. 2,436,668.  
Teva shall pay Pfizer its costs of this application as per Schedule “A”, Agreed Terms  
of Costs Order attached hereto, Paragraph 2 having been deleted as not applicable  
given the result.  
3.  
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  
accordingly.  
“Henry S. Brown”  
Judge  
Page: 150  
Schedule “A”  
Agreed Terms of Costs Order  
1. The successful party will be awarded costs 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 expert’s own  
affidavit/report or preparing for the expert’s 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. one senior and one junior counsel at the hearing;  
ii. one senior and one junior counsel in conducting cross-examinations; and  
iii. one senior counsel in defending cross-examinations;  
g. Travel and accommodation expenses will be assessed on the basis of economy air  
fares and single rooms; and  
Page: 151  
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-1399-15  
DOCKET:  
PFIZER CANADA INC. AND WHETH LLC v TEVA  
CANADA LIMITED AND THE MINISTER OF HEALTH  
STYLE OF CAUSE:  
TORONTO, ONTARIO  
APRIL 3, 2017  
PLACE OF HEARING:  
DATE OF HEARING:  
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  
Nicole Mantini  
Andrew Bernstein  
Rachael Saab  
FOR THE APPLICANTS  
FOR THE RESPONDENTS  
Brian Norry  
Aleem Abdulla  
SOLICITORS OF RECORD:  
Torys LLP  
Barristers and Solicitors  
Toronto, Ontario  
FOR THE APPLICANTS  
FOR THE RESPONDENTS  
Aitken Klee LLP  
Barristers and Solicitors  
Ottawa, Ontario  


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