2011 FC, 2011 FC 1486

Federal Court Cour fédérale Date: 20111206 Dockets: T-644-09 T-933-09 Citation: 2011 FC 1486 Ottawa, Ontario, December 6, 2011 PRESENT: The Honourable Mr. Justice Boivin Docket: T-644-09 BETWEEN: APOTEX INC. Plaintiff and SANOFI-AVENTIS Defendant Docket: T-933-09 BETWEEN: SANOFI-AVENTIS AND BRISTOL-MYERS SQUIBB SANOFI PHARMACEUTICALS HOLDINGS PARTNERSHIP Plaintiffs and APOTEX INC. APOTEX PHARMACHEM INC. AND SIGNA SA de CV Defendants

PUBLIC REASONS FOR JUDGMENT Heard: April 18, 19, 20, 21, 26, 27, 28, 29, May 3, 4, 5, 9, 10, 11, May 16, 17, 18, 19, 24, 25, 30, 31, June 1, 13, 14, 15, 2011 I Introduction A. Preliminary Observations [ 1 ] This case concerns the drug clopidogrel bisulfate, sold in Canada under the brand name Plavix and commercialized as an anticoagulant that inhibits platelet aggregation activity in the blood.

Plavix is the subject of Canadian Patent No. 1,336,777 (the ‘777 Patent) issued on August 22, 1995. [ 2 ] The ‘777 Patent is a selection patent held by Sanofi-Aventis. [1] At the heart of this case lies the issue of the validity of the ‘777 Patent. Sanofi submits that the ‘777 Patent is valid and that it has been infringed by Apotex [2] who manufactures and sells generic clopidogrel. Apotex, on the other hand, submits that the ‘777 Patent is invalid and that there has accordingly been no infringement. [ 3 ] The application leading to the ‘777 Patent was filed in Canada on February 2, 1988.

The Court observes at the outset that pursuant to s 78.1-78.2 of the current Patent Act , RSC 1985, c P-4, as amended, patent applications, such as the one at issue, filed before October 1, 1989 are to be dealt with under the provisions of the Patent Act as they read immediately before that date. Thus, references in these Reasons to the Patent Act (referred to as the Patent Act or the Act), unless specifically noted otherwise, will be to the Act as it stood immediately prior to October 1, 1989. [ 4 ] The Court further notes that this proceeding in fact consists of a consolidation of two actions.

First, there is the impeachment action undertaken by Apotex (T-644-09) and, second, there is the infringement action undertaken by Sanofi (T-933-09). The procedural background in which each of these actions was initiated is summarized next. B. Procedural Background [ 5 ] On March 10, 2003, Apotex served upon Sanofi a Notice of Allegation (NOA) under the Patented Medicines (Notice of Compliance) Regulations , SOR/93-133 (PMNOC Regulations) for the purpose of obtaining a Notice of Compliance (NOC) from the Minister of Health, pursuant to

section C.08.004 of the Food and Drug Regulations , CRC 1978, c 870. As part of its NOA, Apotex alleged that its manufacture and sale of generic clopidogrel bisulfate tablets would not infringe any valid claim in the ‘777 Patent. [ 6 ] In response, Sanofi sought an order prohibiting the Minister of Health from issuing a NOC to Apotex in respect of generic clopidogrel bisulfate tablets until the expiry of the ‘777 Patent. [ 7 ] By Order dated March 21, 2005, Justice Shore of the Federal Court granted Sanofi’s application.

As a result of this Order, the ‘777 Patent prevented Apotex from coming to market with its generic clopidogrel bisulfate tablets in Canada . The Federal Court of Appeal and the Supreme Court of Canada upheld this Order. Apotex accordingly did not obtain a NOC from the Minister of Health. [ 8 ] Following the Order dated March 21, 2005, and related court challenges, the two present actions, now consolidated, were commenced as follows: Apotex’ impeachment action dated April 22, 2009 (T-644-09); and Sanofi’s infringement action dated June 8, 2009 (T-933-09). [ 9 ] In

summary, Apotex’ impeachment action seeks a declaration that the claims of the ‘777 Patent are invalid, void and of no force and effect. Apotex alleges the following grounds of invalidity: ▪ inutility; ▪ lack of demonstrated utility/lack of sound prediction;

▪ obviousness; ▪ lack of novelty/anticipation; ▪ double patenting.

Apotex further seeks a declaration of non-infringement with respect to its generic clopidogrel products. [ 10 ] Conversely, Sanofi’s infringement action seeks a declaration that Apotex has infringed the ‘777 Patent by manufacturing clopidogrel – containing products in Canada for export to other countries, including the United States and that, as a result, Sanofi is entitled to injunctive relief and an accounting of profits or damages. [3] [ 11 ] Apotex’ impeachment action and Sanofi’s infringement action were briefed as follows: Impeachment Action 1. Apotex Statement of Claim dated April 22, 2009; 2.

Apotex Amended Statement of Claim dated May 27, 2009; 3. Sanofi Statement of Defence dated June 8, 2009; and 4. Apotex Reply dated June 18, 2009. Infringement Action 1. Sanofi Statement of Claim dated June 8, 2009; 2. Apotex Second Amended Statement of Defence and Counterclaim dated December 14, 2010; 3. Statement of Particulars dated December 2, 2010 to the Amended Statement of Defence and Counterclaim of Apotex; 4. Statement of Particulars dated December 16, 2010 bis; 5. Sanofi Reply and Defence to Counterclaim dated January 31, 2010; 6.

Statement of Particulars dated April 8, 2010 in Reply to Defence to Counterclaim of Sanofi; and 7. Apotex Amended Reply to Defence to Counterclaim dated April 15, 2011. [ 12 ] On or about July 15, 2009, Sanofi filed a motion to consolidate the impeachment and infringement actions in order for them to be heard together. Apotex indicated its opposition to consolidation in its Statement of Defence and Counterclaim and stated that the infringement action should be stayed. By Order dated November 2, 2009, Prothonotary Tabib, acting as the Case Management Judge, ordered consolidation.

She further ordered bifurcation of the damages issues. [ 13 ] Both actions were accordingly heard together in a trial that commenced on April 18, 2011. During the twenty-six (26)-day trial, a total of twenty-three (23) experts and fact witnesses appeared before the Court. A brief overview of the experts and fact witnesses’ testimony is included in Appendix A. [ 14 ] The key questions to be addressed in this proceeding are as follows:

A) Does Sanofi have standing to bring its infringement action?

B) Has Apotex infringed the ‘777 Patent?

C) Is the ‘777 Patent valid? [ 15 ] As explained in these Reasons, the Court has concluded that:

A) Sanofi has standing to bring its infringement action;

B) The ‘777 Patent was infringed by Apotex; and

C) The ‘777 Patent is invalid. [ 16 ] As a result, Apotex’ impeachment action is allowed and Sanofi’s infringement action is dismissed. II Table of Contents [ 17 ] To assist the reader, the Court has compiled a Table of Contents for these Reasons with page numbers for each heading.

Table of Contents Paragraph I Introduction 2 A Preliminary Observations ............................................................................ 1 B Procedural Background .............................................................................. 5 II The Table of Contents Table of Contents ............................................................................................. 17 III NOC Proceedings NOC Proceedings .............................................................................................. 18 IV Standing 29 A The Parties’ Submissions ............................................................................ 29

(1) The Position of Apotex .................................................................... 29

(2) The Position of Sanofi ...................................................................... 30 B Subsection 55.1 of the Patent Act – General Principles ............................... 33 C The BMS/Sanofi Partnership Agreements .................................................... 40 D The Evidence before the Court .................................................................... 47 E Conclusion on Standing ............................................................................... 57 V Claims Constrution A General Principles ....................................................................................... 58 B The Hypothetical Person of Ordinary Skill in the Art (POSITA) ................... 64 C The Patent Specification .............................................................................. 81 D The Claims at Issue ..................................................................................... 95 E Claims 1, 3, 10 and 11 ................................................................................ 96 F The Limitations of Claims 6 to 9 .................................................................. 102 G What is the Meaning of “Medicine of the Invention”? ................................... 108 H Page 21 of the ‘777 Patent ......................................................................... 119 I The Invention described in the ‘777 Patent ................................................... 133 J The Construction of the Promise of the Patent .............................................. 141

(1) General Principles .............................................................................. 141

(2) Summary of Expert Evidence ............................................................. 147

(3) What Is the Promise of the ‘777 Patent? .............................................. 158 K

Summary on Claims Construction ............................................................... 182 VI Infringement – Background 184 A Introduction ............................................................................................... 184 B General Principles ....................................................................................... 185 C

Summary of Sanofi’s Case on Infringement ................................................. 194 D The Evidence before the Court ................................................................... 198

(1) Product Claims: Claims 1, 3, 10 and 11 ............................................. 211

(2) Process Claims: Claims 6-9 ............................................................... 214 E Potential Exemption from Liability ............................................................... 232

(1) Apotex’ Alleged Experimental Use .................................................... 233 F Apotex’ Defences to Infringement ............................................................... 239

(1) The Limitation Period ........................................................................ 240

(2) The Settlement Agreements and Estoppel Defence ............................. 259 G Conclusion ................................................................................................. 293 VII Validity 294 A Overbreadth ............................................................................................... 295 B Sufficiency .................................................................................................. 303 C Anticipation ................................................................................................ 306

(1) General Principles ................................................................................ 306

(2) The Posters and the Abstracts ............................................................. 312

(3) The ‘875 Patent .................................................................................. 323

(4) The Conclusion in Anticipation ............................................................. 330 D Double Patenting ........................................................................................ 331 E Utility .......................................................................................................... 336

(1) The Lack of Utility ............................................................................... 336

(2) The Demonstrated Utility ..................................................................... 339

(3) The Utility – Sound Prediction ............................................................. 358 (

a) The Promise of the ‘777 Patent ................................................... 358 (

b) The Prediction ............................................................................ 363 (

i) What is the Utility? .............................................................. 363 (ii) The Promise of the Patent ................................................... 367 (iii) Prima Facie Reasonable Inference of Utility ....................... 401 (

c) Factual Basis .............................................................................. 404 (

i) Summary of Chronology ..................................................... 404 (ii) Important Events in Factual Basis ........................................ 441 (iii) Draw-Backs in Factual Basis ................................................ 468 (iv) Conclusion on Factual Basis ................................................. 483 (

d) Sound Line of Reasoning ............................................................ 489 (

i) Stereochemistry .................................................................. 492 (ii) Toxicology .......................................................................... 502 (iii) Haematology ....................................................................... 507 (iv) Pharmacology ..................................................................... 518 (

v) Previous Work on Thienopyridine Compounds ..................... 543 (vi) Extrapolation from Animals to Humans ................................ 556 (vii) Conclusion on Line of Reasoning ......................................... 562 (

e) Disclosure .................................................................................. 564 (

i) Quid Pro Quo – Principles ................................................. 564 (ii) Factual Basis ...................................................................... 569 (iii) Insufficient Disclosure – Essential Elements of Factual Basis Missing ............................................................................. 571 (

a) No Reference to Work Done on Ticlopidine ............. 574 (

b) No Reference to PCR 4099 ..................................... 575 (

c) No Reference to Multiple Animal Models used and Knowledge of Convulsions ....................................... 578 (

d) No Recognition of Importance of Metabolism ........... 580

(4) Conclusion on Disclosure ................................................................... 584 F Conclusion on Sound Prediction .................................................................. 585 VIII Obviousness A General Principles ....................................................................................... 587 B Date of Invention ......................................................................................... 591 C Common General Knowledge ..................................................................... 601

(1) The State of the Art of Science ........................................................... 605

(2) The ‘875 Patent ................................................................................. 608

(3) The Abstracts and Posters at the July 1985 Conference in San Diego and the June 1986 Conference in Jerusalem ............................................... 615

(4) The 1987 FDA Manufacturing Guidelines ........................................... 629

(5) The Ariens

Article .............................................................................. 639

(6) PCR 4099 ......................................................................................... 645 D Test for Obviousness ................................................................................... 648

(1) Identify the Notional “Person Skilled in the Art” ................................ 649

(2) Identify the Relevant Common General Knowledge of that Person ...... 650

(3) Identify the Inventive Concept of the Claim in Question or if that Cannot Readily be Done, Construe It ........................................................... 653

(4) Identify what, if any, differences exist between the matter cited as forming part of the “State of the Art” and the inventive concept of the claim or the claim as construed ......................................................... 654

(5) Viewed without any knowledge of the alleged Invention as claimed, do those differences constitute steps which would have been obvious to the Person Skilled in the Art or do they require any degree of invention? . 657 E “Obvious to Try” Considerations ................................................................. 658

(1) Is it more or less self-evident that what is being tried ought to work? Are there afinite number of identified predictable solutions known to Persons of Ordinary Skillin the Art? ................................................ 663(

a) Methods to Separate ................................................................ 664(

i) What is the “Pasteur Method”? ......................................... 667(ii) Would the Person of Ordinary Skill in the Art turn to this Chiral HPLC?................................................................. 678(iii) Conclusion on Method to obtain Separation ...................... 687(

b) Methods to Obtain Salt Formation ............................................ 694(

c) Conclusion: “Ought to Work” ................................................... 707(2) What is the extent, nature and amount of effort required to achieve theInvention? Are Routine Trials carried out or is the Experimentation prolonged andarduous, such that the trials would not be considered routine?........................................................................................... 709(

a) What is “Routine” in separating the enantiomers of PCR 4099 and obtaining thesalts? ........................................................... 709(3) Is There a Motive provided in the Prior Art to find the Solution the Patentaddresses? ............................................................................ 721(

a) The Motivation to separate: “the Mumblings”of the mid-1980’s 722Event 1: The Thalidomide Disaster .............................................. 725Event 2: The 1985 Japanese Guidelines ....................................... 727Event 3: Dr. Kumkumian’s 1986 Speech ..................................... 729Event 4: The 1987 FDA Guidelines Document and the Stereoisomer’s Committee............................................ 733Event 5: The 1989 Nature

Article and the Pressure for New Drugs 735Event 6: Joint Venture Partner asking about Data on Enantiomer... 738Event 7: The 1992 FDA Policy In Force ..................................... 741(

b) Summary ............................................................................... 743(

c) Conclusion “Motivation” ......................................................... 750(4) Actual Course of Conduct that Culminated in Invention .................... 752(5) Conclusion on Obviousness ............................................................. 783 IX Overall Conclusions Conclusion .................................................................................................. 785 III NOC Proceedings [18] As noted earlier, the parties’ dispute regarding the ‘777 Patent was the subject of a NOC proceeding. Given thecircumstances, the Court considers it apposite to provide a brief overview of these NOC proceedings. [19] Essentially, NOC proceedings consist of a

summary procedure for assessing the validity of a Canadian patent. Suchproceedings are initiated by way of application to the Federal Court of Canada (Sanofi-Synthelabo Canada Inc. v Apotex Inc., 2005 FC 390, 39 CPR (4th) 202). In particular, there is no viva voce testimony from witnesses, and the evidence is accordingly limited to adocumentary record.

Significantly, the PMNOC Regulations do not allow any determinative findings on the validity of the patent per se;the only conclusion to be drawn in the context of NOC proceedings is whether the allegations of patent invalidity are “justified” or “notjustified”. [20] Furthermore, the PMNOC Regulations do not displace the right of a patent holder to bring an action for infringement, aninterested person to challenge the validity of a patent in an action for impeachment (Pharmacia Inc. v Canada (Minister of NationalHealth & Welfare) (1994), (FCA), [1995] 1 FC 588, 58 CPR (3d) 209 (FCA) at 217; Bristol-Myers Squibb Co. v Canada (Attorney General), 2005 SCC 26, 39 CPR (4th) 449 at paras 11-12). [21] As part of the NOC proceedings initiated by Apotex, it was alleged by Apotex that a NOC should be issued because generic

clopidogrel bisulfate did not infringe the ‘777 Patent. In particular, Apotex maintained that the ‘777 Patent was invalid on grounds of obviousness, anticipation and double patenting. [ 22 ] As noted earlier, Apotex was not successful in obtaining a NOC.

Justice Shore, the Applications Judge, rejected all three (3) of Apotex’ allegations of invalidity on the basis that these allegations were not justified. [ 23 ] Apotex appealed the decision of Justice Shore and, on December 22, 2006, the Federal Court of Appeal upheld this decision and accordingly dismissed Apotex’ appeal ( Sanofi-Synthelabo Canada Inc. v Apotex Inc. , 2006 FCA 421 , 59 CPR (4 th ) 46 ). [ 24 ] Justice Noël, writing for a unanimous Federal Court of Appeal, concluded that Apotex had not shown, on a balance of probabilities, that Justice Shore had committed any reviewable errors in arriving at the conclusions on obviousness, anticipation and double patenting. [ 25 ] Thereafter, Apotex appealed to the Supreme Court of Canada.

On November 6, 2008, in Apotex v Sanofi-Synthelabo Canada Inc. , 2008 SCC 61 , 69 CPR (4 th ) 251 (SCC Plavix ) , the Supreme Court of Canada, in a unanimous judgment written by Justice Rothstein, dismissed Apotex’ appeal, again on the issues of obviousness, anticipation and double patenting. In its judgment, the Supreme Court of Canada modified the legal tests for the law of obviousness and anticipation.

A review of the relevant legal principles will be considered later in this decision. [ 26 ] In the context of the present case, Sanofi relied extensively on the decision of the Supreme Court of Canada in the NOC proceedings. However, the NOC proceedings and the fact conclusions they may have yielded are of limited assistance when, as here, the evidence adduced and the issues differ considerably from those presented in the course of the NOC proceedings.

Indeed, unlike the NOC proceedings, the present impeachment and infringement actions, at trial, involved viva voce testimony from nine (9) experts and fourteen (14) fact witnesses. Furthermore, these experts and fact witnesses were heard on a broader range of issues than those considered as part of the NOC proceedings. In particular, many were heard on the issue of sound prediction which, as seen later, is a central question before the Court.

Yet the issue of sound prediction was not addressed as part of the NOC proceedings and there was accordingly no evidenciary record on that issue. [ 27 ] On the issues of obviousness and anticipation, it is equally clear that the evidentiary record before the Federal Court of Canada, the Federal Court of Appeal, and the Supreme Court of Canada differed significantly from the record before the Court.

Thus, whilst the Court recognizes that the legal principles and the questions of law decided by the Supreme Court of Canada in the NOC proceedings must necessarily be followed, the Court is not, however, bound by the factual findings made in the context of the NOC proceedings because the evidence is not necessarily the same. Hence, the NOC proceedings, whilst instructive, are not fact- determinative.

As further noted by the Federal Court of Appeal, “factual findings are derived from the evidence that is before the court in the particular proceeding” and it is “incumbent upon the judge to arrive at his findings on the basis of the evidence that was before him” ( Ratiopharm Inc. v Pfizer Ltd. , 2010 FCA 204 , 87 CPR (4 th ) 185 , at paras 25 and 26 ). [ 28 ] It follows that NOC proceedings do not constitute res judicata ( Ratiopharm Inc. v Pfizer Ltd. , 2009 FC 711 , 76 CPR (4 th ) 241 , at para 18 ; Eli Lilly Canada Inc. v Novopharm Ltd. , 2009 FC 235 , 73 CPR (4 th ) 253 ).

To put it another way, NOC proceedings are not the gospel. IV Standing A. The Parties’ Submissions

(1) The Position of Apotex [ 29 ] Apotex submits that one of the plaintiffs in this case, namely Bristol-Myers Squibb Sanofi Pharmaceuticals Holding Partnership (the Partnership), has no standing to bring the present action to the extent it relates to any acts of infringement alleged to have taken place prior to June 12, 2007, the date on which the Amendment to Clopidogrel Intellectual Property License and Supply Agreement (the Amended IP Agreement) was entered into between Sanofi and the Partnership.

It is Apotex’ position that the Partnership had no explicit licence prior to the Amended IP Agreement and that, furthermore, such an amendment cannot be applied to confer rights retroactively. Apotex argues that the Partnership is not the active entity that carries on in the foreign jurisdictions at issue and Apotex also argues that the Partnership does not operate in Canada . This, according to Apotex , bars the Partnership from seeking recovery in the form of damages in the circumstances.

(2) The Position of Sanofi

[30] In response, Sanofi asserts that, on the basis of its ‘777 Patent, there can be no question that it has standing to sue forinfringement and obtain a remedy.

As for the Partnership, Sanofi submits that it is an exclusive licensee under the ‘777 Patent and thatthe Partnership consequently has standing to sue for infringement and obtain a remedy as described in ss 55(1) of the Patent Act. [31] More particularly, Sanofi argues that the Partnership is a “person claiming under” a patentee as stated in ss 55(1) of the PatentAct because the Partnership is assessing a right under the ‘777 Patent and that can be traced right back to the patentee.

According toSanofi, exclusive and non-exclusive licensees, implied or oral, qualify as a “person claiming under” under a patentee (Jay-Lor, below). [32] In this regard, Sanofi emphasizes that the Partnership has been given an explicit right to use and exploit the subject matter ofthe ‘777 Patent and clopidogrel bisulfate. B. Subsection 55(1) of the Patent Act – General Principles [33] The term “patentee” is defined in s 2 of the Patent Act to mean “the person for the time being entitled to the benefit of apatent”.

Because the patentee has monopoly over his patented invention, he may on this basis assign, licence or give a right to use hispatent either exclusively or non-exclusively, in whole or in part. Significantly, ss 55(1) of the Patent Act provides a damages remedy andhence standing to claim damages not only to the patentee but also to “all persons claiming under the patentee”. Subsection 55(1) providesas follows: 55.

(1) A person who infringes apatent is liable to the patenteeand to all persons claiming underhim for all damages sustained bythe patentee or by any suchperson, by reason of theinfringement. 55.

(1) Quiconque viole unbrevet est responsable, envers lebreveté et envers toute personnese réclamant du breveté, de tousdommages-intérêts que cetteviolation a fait subir au brevetéou à cette autre personne. [34] The question of who qualifies as a person claiming under a patentee pursuant to ss 55(1) of the Patent Act has been analyzednumerous times by Canadian courts.

In the 1972 case, American Cyanamid Company v Novopharm Limited, [1972] FC 739 (FCA), theFederal Court of Canada enlarged the meaning of “persons claiming under” when it held that a non-exclusive licensee of a patent is aperson claiming under the patentee within the meaning of ss 55(1) of the Patent Act. [35] Along the same lines, in Armstrong Cork Canada Ltd. v Domco Industries Ltd., (SCC), [1982] 1 SCR 907,66 CPR (2d) 46, at p 912, the Supreme Court of Canada adopted the comments of Fry L.J. at p 470, in Heap v Hartley, (1889) 42 Ch D461: […] An exclusive license is only a license in one sense; that is to say, the true nature of an exclusive license is this.

It is a leave to do athing, and a contract not to give leave to anybody else to do the same thing. But it confers like any other license, no interest or property inthe thing. […] [36] Another leading case in this regard is Signalisation de Montréal Inc. v Services de Béton Universels Ltée (FCA), (FCA), [1993] 1 FC 341, 46 CPR (3d) 199, where the Federal Court of Appeal analyzed the issue of the rights of someone otherthan the patentee to maintain an action for infringement. In so doing, the Federal Court of Appeal considerably enlarged the pool of“persons claiming under the patentee”.

It held at pp 210-211 that: […] a person “claiming under” the patentee is a person who derives his rights to use the patented invention, at whatever degree, from thepatentee. The right to use an invention is one the monopoly to which is conferred by a patent. When a breach of that right is asserted by aperson who can trace his title in a direct line back to the patentee, that person is “claiming under” the patentee. It matters not by whattechnical means the acquisition of the right to use may have taken place. It may be a straightforward assignment or a licence. It may, as Ihave indicated, be a sale of an

article embodying the invention. It may also be a lease thereof. What matters is that the claimant asserts aright in the monopoly and that the source of that right may be traced back to the patentee. […] [37] More recently, Justice Snider in the case of Laboratoires Servier v Apotex Inc., 2008 FC 825, 67 CPR (4th) 241, at para 77,found that “[t]he ability of a party to claim under a patentee does not necessarily require the existence of an express licence”. She addedthat “[w]here no express licence exists, each case will be determined on its facts to determine whether an implied licence or other rightexists that gives rise to a claim “under the patentee”.

[38] In addition, Justice Snider in Servier, above, at para 70, provided the following guidance: [70] The test for who qualifies as a person claiming under a patentee is not simply whether the patentee has consented to the personbeing joined as a plaintiff in an action; nor is it enough to demonstrate that two parties are related. In each case, the facts mustdemonstrate a credible and legally sufficient basis for claiming under a patentee (Jay-Lor International Inc. v.

Penta Farm Systems Ltd., (2007), 2007 FC 358 , 59 C.P.R. (4th) 228 at paras 31, 36 (F.C.) [Jay-Lor]). [Emphasis added] [39] In light of these principles, the Court now turns to the BMS/Sanofi Partnership Agreements entered into between Sanofi andthe Partnership. C. The BMS/Sanofi Partnership Agreements [40] The Partnership arose from the discovery of clopidogrel and irbesartan, two promising drugs. Because Sanofi had very littlepresence in the United States and Canada, it turned to Bristol-Myers Squibb (BMS) to create a partnership in order to commercialize thecompounds on a worldwide basis.

Sanofi and BMS accordingly entered into a Development Agreement in 1993, as well as a series ofsubsequent agreements including a Partnership Agreement, an Alliance Support Agreement (Territory A and B), a Product Know-HowLicence Agreement and a Clopidogrel Intellectual Property License and Supply Agreement, all of which are dated January 1, 1997. [41] In 2007, the parties decided to revise the initial Clopidogrel Intellectual Property License and Supply Agreement they hadsigned in 1997.

This revised agreement was meant to address the needs of the alliance as the products were moving closer tocommercialization and it included revisions to […] of the initial agreement listing the patent at issue. Thus, an Amendment toClopidogrel Intellectual Property License and Supply Agreement was signed on December 6, 2007. [42] The Court observes that contractual arrangements regarding the Partnership were structured around two territories, commonlyreferred to as Territory A and B.

Territory B covers the United States, Canada, Mexico, South America, Australia and New Zealand,whereas Territory A includes Europe, Africa, the Middle East and Asia. Two territory partnerships were accordingly formed in order tomanage central expenses, such as marketing, research and development and royalties, and to supply the finished product to the individualcountries.

At the country level, agreements either to co-promote or to co-market were also put in place. [43] The Court further notes that the Product Know-How Licence Agreement confers rights to either party in the Partnership withregards to all technical data, information, material and other know-how that relates to the formulation of the products that are developedunder the Development Agreement. [44] As for the Clopidogrel Intellectual Property License and Supply Agreement (1997) as well as the Amended Agreement(2007), it grants an exclusive licence to the Partnership in the following terms: […] [omitted] . [45] [omitted] . [46] Against this background, the Court now turns to the evidence put before it in connection with the rights conferred to thePartnership.

D. The Evidence before the Court [47] During the trial, Dr. Thierry Saugier, Vice-President Alliance and Partnership at Sanofi-Aventis, was called by Sanofi totestify as to the standing of the Partnership. Dr. Saugier testified that, since April 2006, he has managed group of alliances for Sanofi-Aventis, including the alliance referred to the Territory B Partnership and the Territory A Partnership.

[ 48 ] In particular, Dr. Saugier testified that, in order to structure the alliance, Sanofi granted an exclusive licence for clopidogrel to the Partnership, as can be seen in the Partnership Agreements which are still in effect today. The various agreements produced into evidence indeed support Dr. Saugier’s oral testimony as to the rights granted thereunder. [ 49 ] [omitted]: Q. [omitted]? A. [omitted]. Q. [omitted]? A. [omitted]. Q. [omitted]? A. [omitted]. Q. [omitted]? A. [omitted]. [ 50 ] [omitted]: Q. [omitted]? A. [omitted]. Q. [omitted]? A. [omitted]. Q. [omitted]? A. [omitted]. Q. [omitted]?

A. [omitted]. Q. [omitted]? A. [omitted]. Q. [omitted]? A. [omitted]. Q. [omitted]? A. [omitted]. Q. [omitted]? A. [omitted]. [ 51 ] [omitted]. [ 52 ] [omitted]. [ 53 ] [omitted]. [ 54 ] [omitted]:

[omitted]. [55] The Court believes that such a list could not, on a practical point of view, be amended each time a development occurred inconnection with products under research or in a process of a patent application. The terms and scope of the agreement at issue are suchthat […] must be interpreted to encompass newly developed compounds.

To conclude otherwise would fly in the face of the verypurpose of the Partnership Agreements, which was to allow the Partnership to carry out all activities related to the development,manufacturing, sourcing and commercialization of clopidogrel in the specified territory known as Territory B, would otherwise bedefeated. [56] Finally, the Court recalls that counsel for Apotex questioned Dr. Saugier in connection with the absence of manufacturingfacilities, employees and registered place of business in Canada in order to demonstrate the lack of standing.

In light of the breadth of thePartnership Agreements, the Court finds this line of questioning to be of no assistance for the purposes of the standing issue. E. Conclusion on Standing [57] In sum, considering the broad meaning of “persons claiming under” a patentee as referred to under ss 55(1) of the Patent Act,and based on the Court’s review of the Partnership Agreements and the testimony given in that regard, the Court finds that thePartnership has a “credible and legally sufficient basis” for claiming under a patentee in the circumstances.

Indeed, the evidence clearlyshows that the Partnership was granted an exclusive licence for clopidogrel products through the various Agreements as of 1997. Itfollows that the Partnership has standing to bring the action at issue for any infringement that it alleges to have occurred prior toDecember 6, 2007. V Claims Construction A.

General Principles [58] In a patent case such as the one at issue, the Court must first construe the claims of the patent in accordance with the principles of claims construction established by the caselaw (Whirlpool Corp. v Camco Inc., 2000 SCC 67, 9 CPR (4th) 129; Novopharm Ltd. v Janssen-Ortho Inc., 2007 FCA 217, 59 CPR (4th) 116; Canada (Attorney General) v Amazon.com, Inc., 2011 FCA 328, [2011]FCJ No 1621). [59] The Court observes that claims construction is a question of law and must be addressed with a purposive approach in order “toachieve fairness and predictability and to define the limits of the monopoly” (Dimplex North America Ltd. v CFM Corp., 2006 FC 586, 54 CPR (4th) 435, at para 49, aff'd 2007 FCA 278, 60 CPR (4th) 277).

In so doing, the Court is required to read the patent claims with “amind willing to understand” (Whirlpool, above). [60] Conceptually, the claims construction analysis focuses on what a hypothetical person of ordinary skill in the art (POSITA)would have understood the patent to claim (Whirlpool, above, at paras 45, 53).

This, in turn, requires that the Court first determine the requisite skills and expertise for the POSITA (Aventis Pharma Inc. v Apotex Inc., 2005 FC 1283, 43 CPR (4th) 161; Apotex Inc. v SyntexPharmaceuticals International Ltd, (FC), [1999] FCJ No 548, 166 FTR 161, at para 38, (QL) (FCTD)). [61] Furthermore, as the patent should be read as a whole, the claims should be read in light of the description in the specification,assisted by experts as to the meaning of technical terms used therein (Shire Biochem Inc. v Canada (Minister of Health), 2008 FC 538,328 FTR 123, at para 22; Whirlpool, above, at para 45). [62] The Court further recalls that, because the ‘777 Patent was issued under the old Patent Act, all claims are to be construed as ofthe date the patent was granted and issued (Pfizer Canada Inc. v Canada (Minister of Health), 2005 FC 1725, 285 FTR 1, at para 36).

Inthe case of the ‘777 Patent, the relevant date is August 22, 1995. [63] With these general principles of claims construction in mind, the Court now turns to its assessment of the POSITA. B. The Hypothetical Person of Ordinary Skill in the Art (POSITA)

[ 64 ] In assessing the hypothetical POSITA, the Court must define the person or group to whom the ‘777 Patent is addressed. This person is obviously not a real person. As explained by Justice Hughes in Merck & Co v Pharmascience Inc ., 2010 FC 510 , 85 CPR (4 th ) 179 , at para 42 : “[T]hat person is to be unimaginative, but that does not mean that the person is slow-witted or graduated (if at all) at the bottom of the class. Nor is the person the gold medalist who graduated at the top of the class. That person is the average person in the group.

Just as a “reasonable man” is expected to be reasonable, the POSITA is expected to possess the ordinary skill in the art”. [ 65 ] The Supreme Court of Canada considered such a person in Whirlpool , above, at para 74, where Justice Binnie for the Court wrote that the POSITA refers to the hypothetical “ordinary worker” who is reasonably diligent in keeping up with advances in the field to which the patent relates. [ 66 ] In Merck & Co v Pharmascience Inc. , above, at para 35, Justice Hughes further referred to submissions made by the Canadian Group of AIPPI (Association internationale pour la Protection de la Propriété intellectuelle) and to a

summary under Canadian law as to what a POSITA is understood to be: 35. … Q.213

Summary In Canada , the “person of ordinary skill in the art” is the hypothetical person to whom the patent is addressed. This may be a single individual or a group representing different disciplines, depending on the nature of the invention. The person of ordinary skill in the art is deemed to be unimaginative and uninventive, but at the same time is understood to have an ordinary level of competence and knowledge incidental the field to which the patent relates (i.e. the common general knowledge) and to be reasonably diligent in keeping up with advances.

The common general knowledge is that knowledge generally known by persons skilled in the relevant art at the relevant time. Accordingly, it can include knowledge passed amongst people in the field, including information that is not in published form. Likewise, not everything that has been published is within the common general knowledge. Evidence Adduced by the Experts on the POSITA [ 67 ] The Court heard from numerous experts on behalf of both Apotex and Sanofi in connection with the POSITA, as set forth next. Apotex’ Experts [ 68 ] Dr.

Hirsh stated that the ‘777 Patent is addressed to persons skilled in clinical medicine/haematology, biochemistry, chemistry, pharmacology, toxicology, and pharmacy. [ 69 ] Dr. Adger opined that the ‘777 Patent is addressed to a person with skills in chemistry, haematology, toxicology, pharmacology and pharmaceutical formulations. In regard to the issues of chemistry, the person would have post-graduate level training in organic chemistry with special focus in synthetic or medicinal chemistry and/or a combination thereof.

Such a person would also have several years of experience in synthesizing organic pharmaceutical compounds, including resolving racemic drugs or otherwise making single enantiomer medicines. This person would understand basic concepts of stereochemistry, would be generally familiar with techniques for the analysis and separation of enantiomers and would have familiarity with enantiomeric pharmaceutical drugs. [ 70 ] Dr. Levy submitted that the ‘777 Patent covers areas of chemistry, medicine, haematology and platelets, pharmacology, toxicology and pharmaceutical formulation.

Regarding areas of pharmacology, the person the ‘777 Patent addresses is a Ph.D. level pharmacologist with at least several years of working as a pharmacologist. [ 71 ] Dr. Sanders indicated that the patent addresses issues of chemistry, pharmacology, mechanisms of platelet aggregation and thrombosis, toxicology, pharmaceutical formulation, and medicine. He further opined that the patent engages a variety of disciplines, one of which is toxicology.

With regard to toxicology, the person to whom the patent is addressed is a trained toxicologist having a Ph.D. in pharmacology or toxicology together with two or three years of experience in the toxicology of pharmaceutical products. The person could also have a Master’s degree in these fields with about five years of practical experience or a bachelor’s degree in these fields with approximately ten years of experience.

Sanofi’s Experts [ 72 ] Dr. Byrn stated that the ‘777 Patent is primarily addressed to an ordinary person working in the synthesis or formulation of pharmaceutical compounds. Such a person would have at least a bachelor’s degree in chemistry or a related discipline and several years of experience working in a pharmaceutical laboratory synthesizing or formulating pharmaceutical compounds. [ 73 ] Dr. Rodricks agreed that the ‘777 Patent is directed to many different areas including chemistry, toxicology, pharmacology, salts and pharmaceutical compositions.

His understanding is that a person skilled in the art as it relates to the toxicology aspects would have an advanced degree in toxicology or pharmacology, or in biochemistry, or a related subject with additional specific training and experience in the area of toxicology and drug safety, including the evaluation and

interpretation of toxicology data. [ 74 ] Dr. Davies opined that a person of ordinary skill in the art is a pharmaceutical chemist having a bachelor’s or doctoral degree in chemistry or a related discipline and several years of experience working in a pharmaceutical laboratory synthesizing drug compounds. The understanding of the invention of the ‘777 Patent is the knowledge and experience of stereochemistry, chiral separation, and drug discovery are crucial to the understanding of the invention of the ‘777 Patent. Therefore, a pharmaceutical chemist with experience in stereochemistry has this background. Dr.

Davies disagreed that toxicologists and medical doctors are persons to whom the ‘777 Patent is addressed. [ 75 ] Dr. Shebuski indicated that the ‘777 Patent is primarily directed to a pharmaceutical chemist, but also to a pharmacologist and toxicologist to the extent they are asked by the pharmaceutical chemist to conduct testing relating to the compound that the chemist has made. The Court’s Findings on the POSITA [ 76 ] As gleaned from the above, Apotex advances that the POSITA includes not only a pharmaceutical chemist but also a toxicologist, haematologist and medical doctor.

Sanofi, on the other hand, argues that the POSITA is a pharmaceutical chemist. [ 77 ] While the Court agrees with Sanofi and Dr. Davies that the ‘777 Patent is addressed to a pharmaceutical chemist because experience in stereochemistry, chiral separation and drug discovery is key to understanding the ‘777 Patent, the Court cannot agree to an

interpretation of the POSITA limited to a pharmaceutical chemist. This would amount to providing the pharmaceutical chemist with the “loudest voice” ( Merck and Co v Pharmascience Inc ., above). The Court considers that there is more to the understanding of the ‘777 Patent than possessing merely the skill of pharmaceutical chemistry. The ‘777 Patent contains a variety of aspects as emphasized by both Dr. Levy for Apotex and Dr. Rodricks for Sanofi.

In that context, the POSITA has to be approached as a team of persons as opposed to a single person with all the skills. [ 78 ] More particularly, the ‘777 Patent addresses identity and chemical structure of the enantiomer known as the dextro-rotatory enantiomer of methyl alpha-5 (4,5,6,7-tetrahydro (3,2-

C) thieno pyridyl) (2-chlorophenyl)-acetate and its racemate and the levo-rotatory enantiomer. The patent discusses a method for isolating the two enantiomers from the racemic mixture, methods of forming the pharmaceutically-acceptable salts of the two enantiomers and methods of preparing pharmaceutical compositions. [ 79 ] The ‘777 Patent also addresses comparative pharmacological and toxicological properties of the two enantiomers and the racemate.

It further makes reference to their respective ability to be used as medicines in pharmaceutical compositions of particular dosage strengths with respect to the mechanisms of arterial and venous thrombosis that are to be used in treatment of platelet disorders due to extracorporeal blood circuits and the complications of atheroma. [ 80 ] The Court accordingly concludes that the hypothetical person skilled in the art (POSITA) in the case at bar consists of a number of skilled individuals; holding a Ph.D in pharmaceutical chemistry; with several years of experience working in the fields of pharmacology and toxicology; and having good general knowledge of haematology and medicine.

C. The Patent Specification [ 81 ] Having established the POSITA, the Court must now consider the patent specification at issue. [ 82 ] The Court notes that the ‘777 Patent is a selection patent. It begins, at page 1, with a general statement of the invention relating to the compound, its process, its preparation and its composition as follows:

The present invention relates to the dextro-rotatory enantiomer of methyl alpha-5 (4,5,6,7-tetrahydro (3,2-

c) thieno pyridyl) (2- chorophenyl)-acetate, a process for its preparation and pharmaceutical compositions containing it. [ 83 ] The patent further specifies that the compound of the invention contains a pyridine ring, a phenyl ring, a chiral center and an H-bonding group.

The compound of the invention corresponds to the following formula: [ 84 ] At page 1 of the Patent, at line 25, the inventors distinguish their invention from the prior art and further specify at line 29 that the invention also relates to salts: In an unexpected manner only the dextro-rotatory enantiomer I d exhibits a platelet aggregation inhibiting activity, the levo-rotatory enantiomer I l being inactive. Moreover, the inactive levo-rotatary enantiomer I l is the less well tolerated of the two enantiomers. The invention also relates to the addition salts of the compounds of formula (I

d) with pharmaceutically acceptable mineral or organic acids. [ 85 ] At page 2 of the Patent, the inventors begin a discussion on salts. They mention that some of the salts of the dextro-rotatory enantiomer I d are sometimes difficult to handle on an industrial scale because they precipitate in an amorphous form and/or they are hygroscopic. However, at page 2, at line 10, it is said that salts have been found that crystallize easily, are not hygroscopic and have good water solubility: Among the mineral and organic acid salts of the dextro-rotatory isomer of the compound of Formula (I

d) salts have been found which crystallize easily, are not hygroscopic and are sufficiently water-soluble as to make their use as active medicinal principles particularly advantageous. [ 86 ] Specifically, the inventors explain that “[t]he present invention thus relates more particularly to the hydrogen sulfate, the taurocholate and the hydrobromide of the dextro-rotatory enantiomer of methyl alpha-5 (4,5,6,7-tetrahydro (3,2-

c) thieno pyridyl) (2- chlorophenyl)-acetate”. [ 87 ] The Court notes that beginning at the bottom of page 7 through to page 11, the inventors go on to provide examples to the reader to illustrate the invention. [ 88 ] Thereafter, at page 12, the Patent discloses the results of a pharmacological study and sets forth another advantage of the invention: A description will now be given of the results of this study which demonstrates another advantage of the invention, namely that the salts of the dextro-rotatory isomer have a better therapeutic index than the salt of the racemic mixture; in fact, the levo-rotatory isomer exhibits almost no platelet aggregation inhibiting activity and its toxicity is markedly higher than that of its dextro-rotatory homologue. [ 89 ] The result of the pharmacological study is described in four (4) distinct Tables: ▪ Table I, at page 14, relates to platelet aggregation inhibiting activity assay using ADP.

According to the patent, the data “demonstrate that the levo-rotatory isomer is inactive and that the dextro-rotatory isomer [clopidogrel] is at least as active as the

racemate”. ▪ Table II, at page 16, relates to platelet aggregation inhibiting activity assay using collagen, the results “demonstrate again that only the dextro-rotatory isomer [clopidogrel] is active whereas the salts have comparable activities”. ▪ Table III, at page 18, relates to the antithrombotic test. According to the patent, the results “show that the levo-rotatory isomer is inactive in this test, in contrast to the dextro-rotatory isomer [clopidogrel] and the racemate”. ▪ Lastly, Table IV, at page 19, relates to the LD 50 test.

According to the patent, the results “show on the one hand that the toxicity of the racemic mixture is similar to that of the levo-rotatory isomer whereas the dextro-rotatory isomer [clopidogrel] is markedly less toxic, and, on the other hand, that the toxicity depends on the nature of the acid used to form the salt”. [ 90 ] Following the four (4) above-described tables, the ‘777 Patent at pages 12 to 19 sets out three (3) different tests performed on female rats: Test no. 1: the compounds were administered to groups of five female rats of the CD-COBS strain and then blood samples were taken from the animals after the compounds have been metabolized in the rats for two hours.

Platelet rich plasma was then isolated and aggregation is induced either with ADP (the ‘777 Patent, Table 1) or collagen of type 1 (the ‘777 Patent, Table II). Aggregation of the platelets was then monitored and a curve is generated to represent a change in optical density. This type of test is known as an ex vivo test because although compounds were administered to animals and blood removed, the test was performed outside of living animals. The results of the tests are reported in Tables I and II.

Test no. 2: this test was inspired by the test developed by Kumada in 1980 ( Kumada et al . “Experimental model of venous thrombosis in rats and effect of some agents” 1980, Thrombosis Research 18; 189-203). It is an in vivo test and was performed by inserting a steel wire into the inferior vena cava of a rat. After a period of time a thrombosis develops on the wire and the weight of the thrombus is measured in untreated rats and those treated with the test compound.

The difference in weight of thrombosis formed with and without the administration of various drugs is used as a measure of the antithrombotic of the test compound. It is also known as the AV/Shunt model. The results of this test are presented in Table III. Test no. 3: The third test was the LD 50 test. This test is an acute toxicity test where the measured endpoint of the experiment is death in 50% of the animals treated. The lethality is a response that occurs at very high doses with a single administration.

The results are in Table IV. [ 91 ] Then at page 20 at line 4, the Patent explains how the invention can be used: The medicine of the invention can be made available for oral administration in the form of tablets, sugar-coated tablets, capsules, drops, granules or a syrup.

It can also be made available for rectal administration in the form of suppositories or for parenteral administration in the form of an injectable solution. [ 92 ] Further, at page 20 at lines 15 to 35, the Patent makes reference to some pharmaceutical formulations of the medicine of the invention for tablets, sugar-coated tablets, capsules, injectable solution and suppositories. [ 93 ] Finally, at page 21, on which there is a sole paragraph, reference is made to medicine of the invention as follows: On account of its interesting inhibitory properties towards platelet aggregation and its interference in the mechanism of formation of arterial and venous thromboses, the medicine of the invention can be usefully administered in the treatment and prevention of platelet disorders due to extracorporeal blood circuits or the consequence of complications in atheroma.

[ 94 ] The Court now turns to the Patent claims at issue. D. The Claims at Issue [ 95 ] By way of a preliminary observation, the Court notes that the ‘777 Patent has eleven (11) claims and they are set forth at pages 22 and 23 thereof. These claims can be grouped as follows: ▪ Claims 1 to 5 relate to clopidogrel and its salts; ▪ Claims 6 to 9 relate to the process of making clopidogrel; ▪ Claims 10 and 11 relate to the pharmaceutical compositions.

The Court observes that there are a number of areas of disagreement between Apotex and Sanofi which are the following: ▪ The Purity of Claims 1, 3, 10, 11; ▪ The Limitations of Claims 6 to 9; ▪ What is the meaning of “Medicine of the Invention”; ▪ Page 21 of the ‘777 Patent; and ▪ The Invention described in the ‘777 Patent. E. Claims 1, 3, 10 and 11 [ 96 ] The only relevant issue with respect to the construction of Claims 1, 3, 10 and 11 concerns the degree of enantiomeric purity of the clopidogrel referred to in these claims.

Apotex submits that the disclosure of the racemate discloses clopidogrel that is 50% pure. The ‘777 Patent contains no purity limitation. [ 97 ] The ‘777 Patent at page 7 discusses the determination of the enantiomer (optical) purity of the dextro-enantiomer and the levo-enantiomer. It further states that, under the conditions described, the optical purity is at least equal to 96% for the dextro-rotatory enantiomer and at least equal to 98% for the levo-rotatory enantiomer. [ 98 ] From this observation, the experts for both parties (Dr. Byrn, Dr. Hirsh and Dr.

Adger) agreed that the purity of the clopidogrel claimed in the ‘777 Patent - although not 100% pure - is “substantially pure”. [ 99 ] Furthermore, Dr.

Hirsh testified that the number of at least equal to 96% for the dextro-rotatory enantiomer, and 98% for the levo-rotatory enantiomer and with respect to the optical purity is relative to the limit of detection. [ 100 ] On this basis, and given that the independent claim has been construed as “substantially pure”, the Court concludes that the dependent claims should also be construed as “substantially pure”. [ 101 ] Hence, the Court finds that a POSITA would conclude that Claim 3 encompasses “substantially pure” hydrogen sulfate salt of clopidogrel. F.

The Limitations of Claims 6 to 9 [ 102 ] As mentioned above, Claim 6 relates to the general process of making clopidogrel and its pharmaceutically acceptable salts. This general process can be summarized as follows: ▪ formation of a salt of the racemate with an optically active acid in a solvent; ▪ performing repeated recrystallizations of the salt until a product of constant optical rotatory power is obtained; ▪ liberation of the salt by a base; and, if desired;

▪ formation of a salt with a pharmaceutically acceptable acid. [ 103 ] Apotex’ argument in this regard is articulated as follows: Claim 6 claims a general process, the Pasteur method referred to by many experts as the classic method, starting with the racemic mixture. Claim 7, then, narrows it where it is the levo-rotatory camphor-10-sulphonic acid that is used, a standard acid. Claim 8 then narrows Claim 6 to use the solvent acetone. And Claim 9 deals with comprising the formation of a salt in acetone.

In sum, Apotex’ view is that claims should not just be read by themselves, but in conjunction with the disclosure, because the claims on their own sometimes fail to tell enough. [ 104 ] In this case, the Court is not persuaded by Apotex’ argument. [ 105 ] Rather, a claim comparison and differentiation indicates that Claim 6 of the ‘777 Patent should be read, compared and contrasted with Claims 7 to 9. Indeed, Claims 7 to 9 also relate to the making of clopidogrel and its pharmaceutically acceptable salts.

A reading of Claims 7 to 9 confirms that they include specifications with respect to the solvent and optically active acid used. More particularly, Claim 7 relates to the process as described in Claim 6, but the optically active acid is specified as being levo-rotatory camphor-10-sulfonic acid. Claim 8 relates to the process as described in Claim 6, but specifies the solvent used in the recrystallization steps as acetone.

Claim 9 relates to the process as described in Claim 6, but specifies the solvent used in the formation of a salt as acetone. [ 106 ] Apotex nonetheless appears to allege that Claim 6 is limited to the acid and solvents discussed in Claims 7 to 9. The Court does not agree. [ 107 ] The Court recalls that the Supreme Court of Canada in Whirlpool , above, at para 49, emphasized that patent claims “must be read with a mind willing to understand”. Reading Claim 6, as proposed by Apotex, disturbs the flow and distorts the logic of the process claims ( i.e.

Claims 6 to 9) and this runs counter to the Supreme Court of Canada’s interpretative guidance. Indeed, what would be the purpose and the relevance of the more specific Claims 7 to 9 if the more general process Claim 6 was limited in the manner suggested by Apotex? The Court also notes that, at page 2, the ‘777 Patent mentions that the levo-rotatory camphor-10-sulfonic acid is “advantageously used” and that acetone is “ideally suited”. This wording implies that other acids and solvents could be used as well.

Hence, bearing in mind the guiding principles enunciated in Whirlpool , above, and, upon reading Claims 6 to 9, the Court finds that a person skilled in the art would construe Claim 6 as not limiting the “optically active acid” to levo-rotatory ( R )-camphor-10-sulfonic acid (Claim 7) and not limiting the solvent to a particular one. In sum, Claim 6 includes the use of optically active acids and solvents that result in the preparation of substantially pure clopidogrel and its pharmaceutically acceptable salts following the process described in Claim 6. G.

What is the Meaning of “Medicine of the Invention” ? [ 108 ] The Court recalls that Apotex argues that the ‘777 Patent addresses matters of medicine, whereas Sanofi maintains that the ‘777 Patent refers to clopidogrel as a compound rather than a medicine. [ 109 ] Where there are technical terms in a patent, the Court is assisted by experts as to the meaning of such terms. The term the “medicine of the invention” as referred to in the ‘777 Patent is one such technical phrase that must be interpreted by the Court ( Shire Biochem Inc. , above, at para 22 ; Whirlpool, above, at para 45).

Indeed, the meaning of the phrase “medicine of the invention” informs the promise of the patent and must be ascertained at this stage of the analysis before the promise of the patent can be determined. [ 110 ] Central to this debate are also the meaning and use of the phrase “medicine of the invention” as well as “compound of the invention”. [ 111 ] In order to address this issue, the Court must look to the wording of the ‘777 Patent and weigh the experts’ opinions. [ 112 ] First , the ‘777 Patent.

The patent in referring to clopidogrel uses the terms “compound of the invention”, “derivative of the invention” and “medicine of the invention”.

[ 113 ] At page 13, the ‘777 Patent, in the context of its discussion on salts, states the following: Among the mineral and organic acids salts of the dextro-rotatory isomer of the compound of Formula (Id) salts have been found which crystallize easily, are not hygroscopic and are sufficiently water-soluble as to make their use as active medicinal principles particularly advantageous . [Emphasis added] [ 114 ] Also, at page 20, the ‘777 Patent specifies that the medicine of the invention “can be made available for oral administration in the form of tablets, sugar-coated tablets ...”.

The patent further specifies the unit doses for the compositions and the daily doses to be administered to patients to treat the disorders addressed by the patent. [ 115 ] Second , the experts. The experts opined on the significance of the meaning of the terms the “medicine of the invention”. For instance, in his report, at para 74, Dr. Davies stated that “[t]he invention of the ‘777 Patent improved PCR 4099 molecule by removing the enantiomer that contributed toxicity but no activity, thus providing a safer, more effective drug ”. (Emphasis added) [ 116 ] The exchange between counsel for Apotex and Dr.

Shebuski is also instructive as to whether the “medicine of the invention” is clopidogrel as described in the ‘777 Patent (Shebuski, cross T5281-5294): Q. Dr. Shebuski, you will agree with me that clopidogrel is a medicine? A. Yes, sir. Q. Thank you. I want to ask you about the ‘777 Patent. Could you open it? A. I have it open, sir. Q. Perfect. You were anticipating my next move. A. I’m on page 21. Q. If you go to page 23 with me, I want to ask you about claims 10 and 11. You talk about those in your paragraphs 41 and 42.

Claim 10 begins with the words “A pharmaceutical composition.” Am I correct that a skilled person reading this would understand that pharmaceutical refers to a drug or a medicine? A. Yes, sir. Properly formulated. Q. Properly formulated. And it’s a drug or medicine that’s intended to be given to people? A. It could be given to animals, as well, as a veterinary product. Q. Okay. You may have just anticipated this. The composition is the formulation or the thing that’s going to deliver the medicine to the patient? A. That’s correct.

Composition could include the salt or the carrier or other excipients that were involved with the active ingredient, which we call the API or active pharmaceutical ingredient. Q. If we go forward, we’re told that the pharmaceutical composition comprises an effective amount of a compound according to claim 1. I want to ask you about the compound according to claim 1. That would be understood to be a reference to clopidogrel and its pharmaceutically acceptable salts, which are described in claim 1. Correct? A. Yes, sir. Q.

When it says “an effective amount of clopidogrel and its pharmaceutically acceptable salts,” I take it the words “effective amount” reveal the concept of an amount that’s sufficient to treat whatever it is you're wanting to treat with the composition? A. Well, my analysis of it is slightly different. The effective amount is the amount that inhibits platelet aggression, which relates to the utility of this patent. Q. What amount of platelet aggregation? In the abstract? Any amount? A. Well, an effective amount.

As I mentioned earlier in my testimony, we look at inhibition levels of 50 percent or greater as an effective amount. Q. Where is that said in the patent? A. It’s not said in the patent. That’s my own conjecture, sir. Q. Conjecture. Okay. I’m going to suggest to you that, given that we are talking about a pharmaceutical composition, when it says,

“ Such a composition comprising an effective amount of clopidogrel and its pharmaceutically acceptable salts,” you have already told me clopidogrel is a medicine, so I’m going to suggest to you it’s an effective amount of the medicine to be able to do what the medicine is supposed to do. Do you agree with that? A. I have no basic disagreement with that. [Emphasis added] [ 117 ] Dr. Hirsh was also inclined to state that the “medicine of the invention” relates to clopidogrel and Dr.

Levy was of the view that a compound, when active, can be a medicine even before it is formulated. [ 118 ] Thus, on the basis of the terms used in the ‘777 Patent, as well as the experts’ opinion on behalf of both Sanofi and Apotex, the Court agrees with Apotex and concludes that matters of medicine in the ‘777 Patent are “inescapable”. The Court accordingly finds that the “medicine of the invention”, as referred to in the ‘777 Patent, relates to clopidogrel. H.

Page 21 of the ‘777 Patent [ 119 ] Another issue in dispute between the parties is the meaning of page 21 of the ‘777 Patent, which is an issue the Court needs to address as it will inform the promise of the Patent. [ 120 ] Page 21 of the ‘777 Patent contains one paragraph and it reads as follows: On account of its interesting inhibitory properties towards platelet aggregation and its interference in the mechanism of formation of arterial and venous thromboses, the medicine of the invention can be usefully administered in the treatment and prevention of platelet disorders due to extracorporeal blood circuits or the consequence of complications in atheroma. [ 121 ] The positions of the parties regarding the above could not be further apart.

Indeed, Apotex ’ position is that page 21 of the ‘777 Patent guarantees treatment in humans whereas Sanofi’s position is that page 21 of the ‘777 Patent does not in any way make reference to treatment in humans or, if it does, only to the “potential” for use in humans. [ 122 ] The expert evidence on this issue has not convinced the Court that the ‘777 Patent guarantees treatment of arterial and venous thrombosis as alleged by Apotex. The Court is equally unconvinced that the ‘777 Patent may refer to the “potential” for use in humans as alleged by Sanofi.

A review of the testimony of the experts simply does not support either of the opposite views expressed by the parties at trial. [ 123 ] Whilst the ‘777 Patent does not refer to a guarantee, it does refer to more than a remote “potential” in humans. Unable to accept either of the two extreme

interpretations of page 21 urged by the parties, the Court finds that the ‘777 Patent makes reference to use in humans. [ 124 ] The Court recalls that Dr. Hirsh, an expert for Apotex , in cross-examination, could not firmly conclude that page 21 of the ‘777 Patent promised treatment of venous thrombosis (Hirsh, T671-674): Q. And to the extent your report says that the patent promises treatment of venous thrombosis, that’s a bit of an inflation? A. Could I see where I said that? Q. Well, yes, sure. I mean if you don’t say it in your report, that’s fine. But let me find it.

Well, for instance in paragraph 188 you are referring to ticlopidine and the racemate, but you do use the phrase prevention and treatment in venous thrombosis. That’s paragraph 188, right at the bottom of the page, the top of the next page, page 64. A. Yes, but that’s a slightly different context isn’t it. Q. And that’s why, but when I read that I was saying, “well, why are you talking about treatment of venous thrombosis if the triple 7 doesn't promise that”? A. It’s just a statement of fact .

Q. Fair enough . A. It’s a statement of fact, but I didn’t say it promised it . I was aware it was a mechanism. The only reason I would be interested in the mechanism would be if it had any utility, but that's implied rather than explicit. [Emphasis added] [ 125 ] However, Dr. Hirsh further testified that clopidogrel has a role in the mechanism of the formation of arterial and venous thrombosis (Hirsh, T682): Q. Let’s turn to the mechanism of formation of arterial and venous thrombosis which are the words that do appear. A. Yes. Q.

I think you have already testified that platelets are involved in the formation of arterial and to a lesser degree venous thrombosis? A. Were they--yes, I have. Q. So if you have an inhibitor of platelet aggregation, its role in the mechanism of the formation of arterial and venous thrombosis is to prevent aggregation? A. Correct. Q. And that’s all it’s saying here? A. I see, um hmm. [Emphasis added] [ 126 ] Dr.

Davies, on behalf of Sanofi, in his report at para 246, opined, with respect to page 21 of the ‘777 Patent, that it was not to be understood as a guarantee for use in humans: Consequently, when I read the entire paragraph on page 21, what is being said is that the improvement in activity and toxicity (based on animal testing) means that the medicine of the invention (i.e. if and when the compound is used as medicine) can (i.e. has potential) to be used for treatment. This is exactly what a skilled pharmaceutical chemist would take from the information in the patent.

It would not be understood to be a promise of clinical approval, or a guarantee of use in humans. [ 127 ] During the evidentiary phase of the trial, Dr. Davies elaborated on the above (T4425-4426): Q. In 246, you give your understanding of the last part of that paragraph on page 21. What is your understanding that you’re telling us there? A. What I’m saying there is, if you read the whole paragraph, the utility, from the first part of the paragraph, is the platelet aggregation inhibition. The rest of the paragraph suggests a potential use perhaps of that platelet inhibition. Q. Thank you.

In paragraph 247, you refer to the claims and you make a comment that there's no use for treatment in humans. I think we’re all aware of that, but you refer then to claims 10 and 11? A. Yes. Q. What are you telling us in connection with claims 10 and 11? A. Claims 10 and 11 talk about pharmaceutical composition involving the clopidogrel as the constituent of that composition, but don't imply any use of that in humans.

It could be in animals, for example. [Emphasis added] [ 128 ] In light of its earlier finding with respect to the meaning of the phrase “medicine of the invention”, the Court cannot accept such a restrictive reading down of the meaning of page 21 of the ‘777 Patent, as suggested by Dr. Davies. The Court refers mutatis mutandis to the comments expressed by Justice Snider in Sanofi-Aventis Canada Inc. v Apotex Inc, , 2009 FC 676 , 77 CPR (4 th ) 99, ( Ramipril ) , (decision affirmed on November 2, 2011 by the Federal Court of Appeal), at para 128: [128] This passage demonstrates that Dr.

Bartlett has not construed the claims in light of the promised utility; rather he has modified or

read down the promise of the patent to suit his understanding of the claims. I cannot accept this reasoning. Such an approach to the question of the promise of the patent excuses the inventors from any requirement of precision in their claims or in the patent specification. If a patentee promises a particular result, he should be held to that promise.

In expressing this view, I am not requiring commercial success or a certain level of commercial development to have taken place. … [ 129 ] In the present circumstances, the language used at page 21 of the ‘777 Patent is not clear as to whether or not it guarantees that clopidogrel will “prevent” or “stop” the “mechanism of formation of arterial and venous thromboses”.

There is simply no explicit wording to this effect. [ 130 ] Yet, the wording in the ‘777 Patent does not make it clear that the purpose is not for humans and the Court is not convinced that page 21 of the ‘777 Patent merely describes a “potential” use for humans. [ 131 ] In sum, the Court finds that Apotex is looking to inflate the meaning of page 21 of the ‘777 Patent, whereas Sanofi is urging that it be read down. It is difficult if not impossible to conclude that page 21 of the ‘777 Patent clearly makes reference to a guaranteed treatment in humans.

It is equally difficult to find that page 21 of the ‘777 Patent does not in any way make reference to treatment in humans. The Court is thus not prepared to conclude that page 21 of the ‘777 Patent is stripped of all reference to humans as advanced by Sanofi. How could this be when the diseases referred to at page 21 of the ‘777 Patent are not in animals but in humans (Hirsh, T391- 393)?

It necessarily means that it has a human purpose of some kind. [ 132 ] The Court accordingly concludes that the reference at page 21 of the ‘777 Patent that “the medicine of the invention can be usefully administered in the treatment and prevention of platelet disorders due to extracorporeal blood circuits or the consequence of complications in atheroma” confirms that clopidogrel on account of its properties, whilst not a guarantee, promises more than a mere potential: it can be used in the treatment of certain human thrombotic diseases. I.

The Invention described in the ‘777 Patent [ 133 ] The Court observes that there is no issue between the parties with respect to the inventive concept of the ‘777 Patent.

The inventive concept was described as follows in the Supreme Court of Canada of the ‘777 Patent in the Plavix decision, at para 78: [78] In the present case, it is apparent that the inventive concept of the claims in the ‘777 patent is a compound useful in inhibiting platelet aggregation which has greater therapeutic effect and less toxicity than the other compounds of the ‘875 patent and the methods for obtaining that compound. [ 134 ] The ‘777 Patent is a selection patent ( i.e. as stated in Plavix it is “one whose subject matter (compounds) is a fraction of a larger known class of compounds which was the subject matter of a prior patent”).

Thus the Court must now address the question of how the inventive concept relates to the invention. More particularly, the question is the following: Do the salts and the advantages form part of the invention?

Sanofi argues that the salts and the advantages could only relate to Claim 3 and the bisulfate salt, whereas Apotex maintains that the salts and their advantages related to the invention described in the ‘777 Patent. [ 135 ] In Olanzapine , below, at para 78, the Federal Court of Appeal provided helpful guidance with respect to selection patents in the following: [78] With respect to selection patents, the inventiveness lies in the making of the selected compound, coupled with its advantage or advantages, over the genus patent.

The selection patent must do more, in the sense of providing an advantage or avoiding a disadvantage, than the genus patent. The advantage or the nature of the characteristic possessed by the selection must be stated in the specification in clear terms… [ 136 ] Thus, whilst in the context of a selection patent, the advantages will often necessarily form part of the invention, other scenarios remain possible. For example, the Court could hypothetically envisage a selection patent relating to the invention of a new process .

In such a case, the new process could be found to be a second invention independent of the advantages stated in the selection patent. However, this is not the case with the ‘777 Patent because it relates to only one invention as discussed later in these reasons: ▪ Firstly, the process of splitting the racemate (PCR 4099) into two distinct enantiomers was not achieved through a new process.

The process leading to the two enantiomers (the dextro-rotatory and the levo-rotatory) was performed following the Pasteur method. ▪ Secondly, a reading of the ‘777 Patent confirms that there is only one invention (pp 1 and 25) :

At page 1 the patent states that “[t]he present invention relates to the dextro-rotatory enantiomer of methyl alpha-5 (4,5,6,7-tetrahydro (3,2-

c) thieno pyridyl) (2-chorophenyl)-acetate, a process for its preparation and pharmaceutical compositions containing it”. In an unexpected manner only the dextro-rotatory enantiomer I 1 exhibits a platelet aggregation inhibiting activity, the levo-rotatory enantiomer I 1 being active.

Moreover, the inactive levo-rotatory enantiomer I 1 is the less well tolerated of the two enantiomers. [Emphasis added] [ 137 ] Significantly, the ‘777 Patent at page 1 at line 29 refers to the invention mentioned and further specifies that: “ the invention also relates to the addition of salts of the compound of formula (I 1 ) with pharmaceutically acceptable mineral or organic acids”.

Furthermore, the ‘777 Patent states at page 2 that the advantages provided by these salts include the characteristics of crystallizing easily, of not being hygroscopic and, being sufficiently water-soluble. [ 138 ] The Court thus concludes from the wording of the ‘777 Patent that there is only one invention and the invention relates to salts of the compound and its advantages. [ 139 ] Therefore, the Court cannot agree with Sanofi’s contention that “there is one invention with different aspects, but each claim has to be considered separately within the invention”.

The Court equally rejects the suggestion that the salts and the advantages may be peripheral to the invention. [ 140 ] In

summary, the ‘777 Patent relates to one invention and that can be described as a compound which is useful in inhibiting platelet aggregation, has greater therapeutic effect and less toxicity than the other compounds of t

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