AstraZeneca Canada Inc. v. Apotex Inc.

AstraZeneca Canada Inc. v. Apotex Inc.
Court (s) Database
Federal Court Decisions
Date
2010-06-30
Neutral citation
2010 FC 714
File numbers
T-371-08
Decision Content
Federal Court
Cour fédérale
Date: 20100630
Docket: T-371-08
Citation: 2010 FC 714
BETWEEN:
ASTRAENECA CANADA INC.
AND ASTRAZENECA AKTIEBOLAG
Applicants
- and -
APOTEX INC. AND THE MINISTER OF HEALTH
Respondents
REASONS FOR JUDGMENT
HUGHES J.
[1] This is an application brought by AstraZeneca Canada Inc. and AstraZeneca Aktiebolag (collectively AstraZeneca) under the provisions of the Patented Medicines (Notice of Compliance) Regulations, SOR/93 – 133, as amended (NOC Regulations), for an Order prohibiting the Respondent, Minister of Health, from issuing a Notice of Compliance to the other Respondent, Apotex Inc., for 20 and 40 mg esomeprazole magnesium tablets until after the expiry of Canadian Patent No. 2,139,653 (the ‘653 patent). For the reasons that follow, I will dismiss the application with costs to Apotex at the column 4 level.
THE PARTIES
[2] The Applicants, described as the “first person” in the NOC Regulations, are AstraZeneca Canada Inc., the Canadian licencee and AstraZeneca Aktiebolag the owner, respectively, of the ‘653 patent. They are also sometimes described as “the brand” or “innovators”. The Respondent Apotex Inc. described as a “second person” in the NOC Regulations, is a Canadian generic drug company who wishes to sell a generic version of AstraZeneca’s esomeprazole product in Canada. The Minister of Health is responsible for administering the NOC Regulations and is required to issue a Notice of Compliance to Apotex to sell its generic drug in Canada if this application is dismissed.
THE DRUG AND INSTITUTION OF THESE PROCEEDINGS
[3] AstraZeneca has received a Notice of Compliance to sell a drug in Canada containing esomeprazole magnesium as an active ingredient. This drug is sold under the brand name NEXIUM in 20 and 40 mg strength tablets. It is said to be useful in the treatment of conditions wherein a reduction of gastric acid secretion is required, such as reflux esoplagitis, nonerosive reflux disease and NSAID-associated gastric ulcers.
[4] Apotex wishes to sell a generic version of this drug in Canada and has applied through the Abbreviated New Drug Submission (ANDS) procedure under the Food and Drug Act, R.S.C. 1985, c. F-27 to receive a Notice of Compliance permitting it to do so. In that regard, Apotex as was required by the NOC Regulations served a Notice of Allegation, dated January 17, 2008, on AstraZeneca alleging that the ‘653 patent which AstraZeneca had listed under the NOC Regulations, was invalid, and would not be infringed. Whereupon AstraZeneca commenced these proceedings pursuant to the NOC Regulations to prohibit the Minister from granting a Notice of Compliance to Apotex until the expiry of the ‘653 patent. The issues have been reduced so that what remains for determination is only whether Apotex’s allegations that claim 8 of the ‘653 patent is invalid on a number of grounds, are justified within the meaning of section 6(2) of the NOC Regulations.
[5] By an Order of a Prothonotary of this Court, granted on consent on August 26, 2009, the 24-month statutory stay pursuant to section 7 of the NOC Regulations was extended to September 30, 2010.
HISTORY OF OMEPRAZOLE LITIGATION IN CANADA
.
[6] AstraZeneca has been zealous in enforcing patents that it has secured in Canada relating to omeprazole based products, of which the current application is one.
[7] Apotex has been equally zealous in seeking approval for generic versions of the drug:
In AstraZeneca Canada Inc. v. Canada (Minister of Health), [2006] 2 S.C.R. 560, 2006 SCC 49, the Supreme Court of Canada allowed an appeal from the Court of Appeals which quashed Apotex’s NOC. The Supreme Court held that the Federal Court was correct that Apotex was not required to address the after‑issued patents of AstraZeneca. Here, the Court dealt with a situation where AstraZeneca’s original patent directed to omeprazole had expired, it discontinued its original formulation and had commenced to market a new formulation. Applicants listed under the NOC Regulations, two patents directed to the new formulation. Apotex wanted to market the original formulation and a question arose whether it could do so.
http://scc.lexum.umontreal.ca/en/2006/2006scc49/2006scc49.html
In AB Hassle v. Apotex Inc., 2002 FCT 931, AstraZeneca assumed a patent directed to the coating of omeprazole cores with a subcoat or a coat to provide for enteric release. Apotex was precluded from getting an NOC to sell the product because its Notice of Allegations did not comply with the NOC Regulations. The Court found the NOA deficient in that it lacked detailed statements of the legal and factual basis for the allegation of non-infringement.
http://decisions.fct-cf.gc.ca/en/2002/2002fct931/2002fct931.html
In AB Hassle v. Canada (Minister of National Health and Welfare) (T.D.), [2002] 3 F.C. 221, 2001 FCT 1264, Apotex was granted the NOC because the Court held that the patent would not be infringed. AstraZeneca filed the patent for the use of omeprazole in the treatment of Campylobacter infections. Apotex sought to market omeprazole for another use which would not be for the treatment of Campylobacter infections.
http://decisions.fct-cf.gc.ca/en/2001/2001fct1264/2001fct1264.html
In AstraZeneca AB v. Apotex Inc., 2004 FC 313, the Court dismissed the application and allowed the Minster to issue the NOC to Apotex. The Court held that the patent in issue would not be infringed. Apotex sought approval for its drug containing only omeprazole to be used to treat conditions where the reduction of gastric acid secretions is required. Applicants’ patent covered a combination product containing omeprazole and an antibiotic.
http://decisions.fct-cf.gc.ca/en/2004/2004fc313/2004fc313.html
In AB Hassle v. Apotex Inc., 2003 FCT 771, the Court prohibited the Minister from issuing an NOC to Apotex when the Court held that adding base salts to omeprazole was a novel invention not known or disclosed in prior art.
http://decisions.fct-cf.gc.ca/en/2003/2003fct771/2003fct771.html
AstraZenenca AB v. Apotex Inc., 2005 FCA 183, is an appeal by AstraZeneca from the trial court’s decision to dismiss its application and grant the NOC to Apotex. The Court of Appeal held that Apotex’s NOA was sufficient in its allegations and there were no reversible errors. Apotex had previously submitted and withdrew an NOA which alleged its product would have 70% crystallinity of an amorphous form of omeprazole which would thereby infringe Applicants’ product. The trial court held that since the newer NOA was separate and distinct and Apotex’s product would not infringe the innovator’s product.
http://decisions.fca-caf.gc.ca/en/2005/2005fca183/2005fca183.html
AB Hassle v. Apotex Inc., 2004 FC 379, is an application under the NOC Regulations where two patents claim new uses for omeprazole or its salts to be used in combination with an antibiotic to act as an antimicrobial agent. The application for prohibition was dismissed because Apotex’s product would only comprise omeprazole as its sole active ingredient for use in the reduction of gastric acid secretion.
http://decisions.fct-cf.gc.ca/en/2004/2004fc379/2004fc379.html
AstraZenenca AB v. Apotex Inc., 2006 FC 7, appeal dismissed, the application was dismissed because the Court held that the enteric coating of Apotex’s product made the formulation different and therefore would not infringe AstraZenenca’s product.
http://decisions.fct-cf.gc.ca/en/2006/2006fc7/2006fc7.html
In AB Hassle v. Apotex Inc., 2005 FC 234, the Court granted the prohibition under the doctrine of issue estoppel in that Apotex could have brought its current allegations in a previous proceeding.
http://decisions.fct-cf.gc.ca/en/2005/2005fc234/2005fc234.html
In AstraZenenca AB v. Apotex Inc., 2007 FC 688, the application was dismissed when the Court held the allegations of invalidity were justified in that prior art anticipated the claims in issue and some of the claims did not contain any therapeutic aspects.
http://decisions.fct-cf.gc.ca/en/2007/2007fc688/2007fc688.html
[8] Other generic companies have not been as successful as Apotex. So far, none have been granted an NOC:
In Genpharm Inc. v. AB Hassle, 2004 FCA 413, the Court of Appeal affirmed the trial court’s decision to grant the application for prohibition. Genpharm did not address non-infringement of all the claims in issue where some addressed taking omeprazole in combination with an antibiotic. Therefore, it did not advance the facts to support its allegation of non-infringement of those claims adequately enough.
http://decisions.fca-caf.gc.ca/en/2004/2004fca413/2004fca413.html
In Hassle v. Canada (MNHW), T-366-98, appeal affirmed, the Court granted the prohibition holding that the generic product of RhoxalPharma would include an inert subcoating thereby infringing AstraZeneca’s product.
http://decisions.fct-cf.gc.ca/en/2000/t-366-98_12522/t-366-98.html
In AB Hassle v. Rhoxalpharma Inc., 2002 FCT 780, the Court granted the prohibition because of a concern that doctors would prescribe the generic version of the pill for uses in the treatment of H. pylori infections and other bacterial infections even though RhoxalPharma’s product monograph would specifically state its use is only for the reduction of gastric acid secretions.
http://decisions.fct-cf.gc.ca/en/2002/2002fct780/2002fct780.html
THE WITNESSES AND EVIDENCE
[9] This application, as is common in many NOC applications, began with raising a number of issues, and issues within those issues. AstraZeneca put a number of claims of the ‘653 patent at issue, including claims 3, 7, 8, 27 and 28. Apotex was arguing non-infringement of several of those claims, as well as certain ‘bad faith” arguments arising out of section 53 of the Patent Act, R.S.C. 1985, c.P-4. As a result, there was some evidence filed which subsequently has become irrelevant. As well, the evidence of several witnesses became relevant only in respect of certain matters. I list all the witnesses, both expert and factual, whose evidence was filed by each party.
1. Applicants’ Witnesses – ASTRAZENECA
[10] Applicants filed affidavit evidence from the following Expert Witnesses: Dr. Armstrong, Dr. Davies, and Dr. Nelson. Affidavits from the following fact witnesses were filed: Dr. Larsson, Dr. Andersson, Ms. Feltmate, Dr. Kohl, Dr. Senn-Bilfinger, Dr. von Unge, and Ms. De Abreu.
Dr. Daniel Armstrong – EXPERT
Dr. Armstrong is the Robert A. Welch Professor, in the Department of Chemistry and
Biochemistry at University of Texas at Arlington. He received a B.Sc. in interdepartmental science and math in 1972 from Washington & Lee University, Lexington, Virginia. In 1974, he obtained a Master's of Science in oceanography from Texas A&M University, College Station, Texas. In 1977, he received a Ph.D. in bio-organic chemistry, from Texas A&M University. The focus of his research has been on methods for separating chiral compounds. He has published over 400 peer-reviewed articles in the academic literature and is a lecturer. He is named as inventor or co-inventor in 11 patents.
i. Mandate
Dr. Armstrong was asked: to describe the person of ordinary skill in the art (“POSITA”) to whom the Canadian Patent 2,139,653 (“’653 patent”) is addressed; and to rebut Apotex’s allegations of lack of novelty, lack of invention and willful misleading when looking at the ‘653 patent.
Dr. Stephen Davies – EXPERT
Dr. Davies is the Chairman of the chemistry department at the University of Oxford, where he has been teaching since 1980. He is also currently the Waynflete Professor of Chemistry at the University of Oxford. He earned a B.A. degree in 1973 and a D. Phil. Degree in 1975, both in Chemistry from the University of Oxford. He obtained a D.Sc. degree in Chemistry from the University of Paris in 1980. His research focuses on the preparation of enantiomerically pure compounds. Dr. Davies founded a company, Oxford Asymmetry, Ltd. In 1992 that provides homochiral compounds in commercial quantities.
i. Mandate
Dr. Davies was asked: to describe POSITA to whom the Canadian ‘653 patent is addressed; to explain the ‘653 patent, in particular claims 7 and 8, from the view of the POSITA on December 8, 1994; and to rebut Apotex’s allegations of invalidity of the ‘653 patent, particularly anticipation, lack of invention – obviousness and Section 53 – wilful misleading.
Dr. Wendel Nelson – EXPERT
Dr. Nelson is a professor in the Department of Medicinal Chemistry, University of
Washington, Seattle, Washington. He received a B.S. in Pharmacy from Idaho State College in 1962 and a Ph.D. in Pharmaceutical Chemistry from the University of Kansas in 1965. Since 1965, he has been a Professor at the University of Washington. He considers himself an expert in the area of medicinal chemistry and researches the chemical and stereochemical aspects of the metabolism of cardiovascular drugs.
i. Mandate
Dr. Nelson was asked: to describe POSITA to whom the Canadian ‘653 patent is addressed; to explain the ‘653 patent, in particular claims 7 and 8, from the view of the POSITA on December 8, 1994; and to rebut Apotex’s allegations of invalidity of the ‘653 patent, particularly obviousness and lack of sound prediction.
Dr. E. Magnus Larsson – FACT
Dr. Larsson is currently employed as the Director of the Process Chemistry Group for AstraZeneca AB in Sweden. He was directly involved with research and development of manufacturing processes for the esomeprazole magnesium trihydrate. He is named as an inventor in about 58 patents related to his research. In 1985, he earned an M.S. in chemical engineering at the Royal Institute of Technology in Stockholm. Dr. Larsson received his Ph.D. degree in 1993 in organic chemistry from the Royal Institute of Technology.
i. Mandate
Dr. Larsson was asked to discuss the work he did at AstraZeneca in 1993 with respect to making omeprazole enantiomers using the process identified in the DE 4035455 patent (“DE 455 patent”).
Dr. Tommy Andersson – FACT
Dr. Andersson received a B.Sc. in Biology and a Ph.D. in Clinical Pharmacology in 1979 and 1991, respectively, from the University of Gothenburg, Sweden. In 1979, he joined Hassle AB, now AstraZeneca AB, and worked in the pre-clinical research group in the Pharmacology Department. In 1981, he moved to the clinical pharmacology group where he became involved with omeprazole. In 1993, he was appointed Project Team Leader for the Omeprazole Successor Project at AstraZeneca AB.
i. Mandate
Dr. Andersson was asked: to describe the testing of esomeprazole alkaline salts in the context of the Omeprazole Successor Project at AstraZeneca AB, to describe the metabolic and pharmacokinetic properties of esomeprazole; and the resulting tests and trials that demonstrate these properties and improved clinical effects of esomeprazole magnesium.
Dr. Bernhard Kohl – FACT
Dr. Kohl is currently employed as Senior Director Process Chemistry for Nycomed GmbH in Konstanz, Germany where he supervises 40 people. He earned an equivalent of a masters degree in organic chemistry in 1976 and a Ph.D. in organic chemistry in 1979, both at the University of Munich. Dr. Kohl is named as a co-inventor in the DE ‘455 patent application.
i. Mandate
Dr. Kohl’s mandate is to discuss the developments in research in the proton pump inhibitor field and the developmental history of the DE ‘455 patent application.
Dr. Johann Senn-Bilfinger – FACT
Dr. Senn-Bilfinger is currently employed as a Director of Discovery and Proof of
Concept Development by Nycomed GmbH in Konstanz, Germany. He has been employed by Nycomed, its predecessor Altana Pharma AG and its predecessor Byk Gulden Lomberg Chemische Fabrik GmbH, since 1978. He earned a Diploma degree in chemistry in 1975 from the University of Stuttgart, Germany and completed a doctorate in chemistry at the University of Stuttgart, in 1978. Dr. Senn-Bilfinger is named as a co-inventor in the DE ‘455 patent application.
i. Mandate
Dr. Senn-Bilfinger’s mandate is to discuss the developments in research in the proton pump inhibitor field and the developmental history of the DE ‘455 patent application.
Dr. Sverker Von Unge – FACT
Dr. Von Unge is a principal scientist in the Medicinal Chemistry department at AstraZeneca R&D (formerly Hassle AS) and has been employed there since 1988. He obtained a Master of Science in Engineering in 1983 from Chalmers University of Technology in Sweden. He is named as a co-inventor of the ‘653 patent.
i. Mandate
Dr. Von Unge’s mandate was to discuss his involvement in the developmental history of the ‘653 patent.
Ms. Karen Feltmate – FACT
Ms. Feltmate is the Vice-President of Operations, Business Services and Regulatory Affairs at AstraZeneca Canada Inc.
i. Mandate
Ms. Feltmate provided a copy of Apotex’s Notice of Allegation.
Ms. Jacinta De Abreu – FACT
Ms. De Abreu is a law clerk at Smart & Biggar.
i. Mandate
Ms. De Abreu provides certain documents as exhibits.
2. Respondent’s Witnesses – APOTEX
[11] Respondent filed the affidavit evidence of the following Expert Witnesses: Dr. Heathcock, Dr. Collicott, Dr. Caldwell, Dr. Mayersohn and Dr. Myerson. Affidavits from the following fact witnesses were filed: Dr. Batey, Dr. Bihovsky and Ms. Ebdon.
a. Dr. Clayton Heathcock – EXPERT
Dr. Heathcock is currently the Emeritus Professor at the University of California at Berkeley and Chief Scientist of the Berkeley branch of the California Institute for Quantitative Biosciences. He obtained a Bachelor of Science from Abilene Christian College, Texas, in 1958 and a Ph.D. in Organic Chemistry from the University of Colorado in 1963. His research focuses on the development of new synthetic and natural products in chemistry.
i. Mandate
Dr. Heathcock was asked: to describe POSITA to whom the Canadian ‘653 patent is addressed; to comment on the ‘653; to give a background on racemates and separation techniques; and to comment on various affidavits of Applicants’ witnesses.
b. Dr. Roland Collicott – EXPERT
Dr. Collicott is the owner of ChalPharm Consultancy, which provides consulting services to the pharmaceutical industry in the area of analytical chemistry, including training courses for analytical chemists, drug characterization, chiral and polymorphic
analysis, stability studies, etc. He is an analytical chemist and has worked at Glaxo Group Research Ltd., OSI Pharmasceuticals (UK) Ltd. as well as other companies. He received his Ph.D. in 2002 from Open University.
i. Mandate
Dr. Collicot was asked: to describe POSITA to whom the Canadian ‘653 patent is addressed; to comment on the ‘653; to give a background on chromatography and the separation of enantiomers; and to comment on various affidavits of Applicants’ witnesses.
c. Dr. John Caldwell – EXPERT
Dr. Caldwell is the Dean of the Faculty of Medicine of the University of Liverpool,
England, since 2002. He was also appointed a Pro-Vice Chancellor of the University in 2007. He received a Bachelor of Pharmacy in 1969 from the University of London and a Ph.D. in biochemistry in 1972. In 1987, the University of London awarded him the degree of Doctor of Science (DSc) in pharmacology, for distinctions in drug metabolism.
i. Mandate
Dr. Caldwell was asked: to provide a technical primer on issues of stereochemistry, pharmaceutics, pharmacokinetics and metabolism as would be know by the POSITA as of December 1994 and as of May 1993; to comment on the ‘653; and to comment on Apotex’s allegations of invalidity of the ‘653 patent, particularly lack of invention.
d. Dr. Michael Mayersohn – EXPERT
Dr. Mayersohn is a Professor of Pharmaceutical Sciences, College of Pharmacy,
University of Arizona. He received a Bachelor of Science in Pharmacy from Columbia University in 1966 and obtained a Ph.D. in pharmaceutics from the State
University of New York at Buffalo in 1971.
i. Mandate
Dr. Mayersohn was asked: to describe the POSITA to whom the Canadian ’653 patent is addressed; to comment on the ‘653 patent; and to comment on Apotex’s allegations of invalidity of the ‘653 patent, particularly lack of utility and lack of sound prediction.
e. Dr. Allan Myerson – EXPERT
Dr. Myerson is currently the Philip Danforth Armour Professor of Engineering, in the Department of Chemical and Biological Engineering at the Illinois Institute of Technology in Chicago. He obtained a Bachelor of Science in chemical engineering in May 1973 and Masters and Ph.D. degrees in chemical engineering from the University of Virginia in January 1975 and January 1977, respectively. He is a registered Professional Engineer in New York and Ohio. His research focuses on crystallization from solution.
i. Mandate
Dr. Myerson was asked: to give a background on crystals and crystallization as the POSITA who have known on May, 28, 1993 and December 8, 1994; to describe the POSITA to whom the Canadian ’653 patent is addressed; to comment on the ‘653 patent; and to comment on the prior art as it pertains to statements made in the affidavits of Applicants’ witnesses.
f. Dr. Robert Batey – FACT
Dr. Batey is currently a Professor of Chemistry and the Associate Chair of Undergraduate Studies at the University of Toronto. In 1992, he received a Ph. D. in chemistry from the Imperial College of Science, Technology and Medicine in London.
i. Mandate
Dr. Batey performed an analysis using HPLC on two samples of solid material provided by Respondent in order to determine the enantiomeric excess of each sample.
g. Dr. Ron Bihovsky – FACT
Dr. Bihovsky is an organic chemist. In 2001, he founded Key Synthesis LLC, a chemistry laboratory that performs contract research for pharmaceutical and biotechnology companies, process research, and consulting work in synthetic organic chemistry and medicinal chemistry. He obtained a Ph.D. in chemistry at the University of California Berkeley in 1977.
i. Mandate
Dr. Bihovsky was asked to repeat Examples 5 and 6 in the DE 455 patent as a POSITA would have done on May 28, 1993.
h. Ms. Lisa Ebdon – FACT
Ms. Ebdon is a law clerk employed by Goodmans LLP.
i. Mandate
Ms. Ebdon produced many of Apotex’s documentary exhibits.
3. Unreferred to Witnesses
a. ASTRAZENECA
[12] Dr. Stephen Byrn submitted an expert affidavit that was not referred to in argument. He is a
Professor of Medicinal Chemistry at Purdue University in Indiana. He received a Ph.D. in organic
and physical chemistry in 1970 from the University of Illinois.
i. Mandate
Dr. Byrn was asked to comment on the Apotex’s allegations of non-infringement of Canadian ‘653 patent. In particular, Apotex's assertions that Claim 3 of the '653 Patent will not be infringed because Apotex’s product is not in a crystalline form.
b. APOTEX
[13] Shufeng Lui is an analytical chemist at Apotex whose mandate was to ship samples to Dr. Bihovsky.
[14] Ms. Michele Cossette is a second year student at the laboratory of Dr. Batey. She signed for the shipment and gave it to Dr. Batey’s laboratory.
[15] Farhad Nowrouzi is a third year student at the laboratory of Dr. Batey. He signed for the shipment and gave the bottle received of racemic omeprazole to Dr. Batey.
[16] Dr. John Hems is the Director, Regulatory Affairs, Canada, for the Respondent, Apotex Inc. He provided an affidavit dealing with Apotex’s ANDS submission history.
[17] Ms. Rosa Rahimpour is a scientist employed in the Toronto offices of Goodmans LLP. She was involved with tracking the shipments from Dr. Bihovsky.
4. Uncontested Submissions
[18] No party raised an objection as to the expert evidence of the other party as being properly tendered as expert evidence nor were the qualifications or expertise of such witnesses seriously questioned. I accept, therefore, such evidence as expert evidence.
[19] The parties jointly tendered a book containing the following documents as agreed documents. These documents appear in the Record; therefore, the book was not separately marked as an exhibit. However, it is noted that these documents were accepted as proper evidence without further proof being required:
1. Copy of Apotex’s Notice of Allegation (pages 845 to 915 of the Record);
2. Copy of the ‘653 patent (pages 388 to 416 of the Record);
3. Copy of an agreed-upon English language translation of German Patent Application DE 40 35 455 (the DE ‘455 application) available for public inspection May 14, 1992. A copy of the original document in the German language was also provided. The German language document appears in the Record at pages 250 to 257; the English translation from which the parties and the Court worked is at pages 258 to 276 of the Record;
4. Copy of a scientific article by Erlandsson et al entitled “Resolution of enantiomers of esomeprazole…” appearing in Journal of Chromatography, published in 1990, section 532, no. 2, November 16, 1990, pages 305 – 313 (the Erlandsson article) as appears in the Record at pages 1386 to 1402.
[20] No witnesses appeared before me in person. Transcripts of their cross-examinations were provided. I have no basis for finding that any witness should be considered to lack credibility. Some arguments were raised as to hearsay, which I will deal with below.
HEARSAY
[21] Apotex objects to certain testimony contained in the affidavits of some of the AstraZeneca witnesses as being inadmissible on the basis that it is hearsay. In particular, Apotex objects to the following:
· Paragraph 37 of the Senn-Bilfinger affidavit, page 216 of the Record;
· Paragraphs 58 to 63, 65 and 67 of the Kohl affidavit, pages 145 and 146 of the Record; and
· Paragraphs 32 to 36 of the Larsson affidavit, pages 230 and 231 of the Record.
[22] Each of the above passages are objected to by Apotex on the basis that the witness is attesting that certain scientific work was carried out and certain results were achieved or not achieved however, that work was not done by the person swearing the affidavit, but by someone else.
[23] AstraZeneca replies by saying that the work was supervised by and done in conjunction with the person swearing the affidavit, and done in the normal course of the duties of the affiant and the persons carrying out those tasks. AstraZeneca points to evidence tendered by Apotex’s witness Dr. Bihovsky, where certain tests were conducted by others and accepted by Dr. Bihovsky. AstraZeneca does not object to that evidence.
[24] I have read the portions of the affidavits objected to and the portions of the transcripts of the cross-examination of those witnesses. I have no hesitation in ruling inadmissible paragraph 37 of the Senn-Bilfinger affidavit in which he speaks about certain results recorded in Dr. Kohl’s notebook, as it is clear from the answers he gave during his cross-examination at pages 14 to 16, 40 to 46 and 54 to 57, that he knew nothing of the Kohl notebook in question or what is recorded there.
[25] As to the other evidence to which objection is taken, the relevant portions of the transcripts of the cross-examination (Kohl: pages 13, 14, 24, 25, 64 to 66, 71 to 77, 81, 82, 96 to 99) (Larsson:
pages 43 to 45, and portions of Niman’s notebook) satisfy me that AstraZeneca’s representation of the facts is correct, those affiants did supervise the work done by others in the normal course of the duties of each of them.
[26] Apotex relies on Rule 81 of this Court to state that affidavit evidence shall be confined to facts within the personal knowledge of the deponent. It also relies on the decision of the Federal Court of Appeal in Canadian Tire Corporation Limited v. P.S. Partsource Inc., 2001 FCA 8 in arguing that while a Court may relieve a party from the obligations of Rule 81, it must do so by way of a motion brought before the hearing with a showing that the evidence is reliable and necessary. The decision of Mosely J. of this Court in Pfizer Canada Inc. v. Apotex Inc. (2007), 61 C.P.R. (4th) 305, at paragraphs 112 to 115 is to the same effect.
[27] I am guided by Sopinka, Lederman& Bryant “The Law of Evidence in Canada”, 3rd ed., LexisNexis in dealing with Apotex’s objection. At pages 269 and 270 of Sopinka, there is a discussion respecting the flexible approach that a Court must take in looking at objections of this sort. The Court should not be pigeon-holed by a set of rules respecting reliability and necessity. Flexibility does not mean that admissibility is limitless, but the Court must be guided by the circumstances of each case. At pages 283 to 291 of Sopinka, there is a discussion as to the common law rule respecting admissibility of business records. There is such a rule to the effect that business records made in the ordinary course contemporaneously with the events, without motive or interest to misstate the facts, are admissible. To some extent, this rule was at one time hampered by a requirement that the person making the record be deceased, but this appears no longer to be the case. To a large extent the matter may be overshadowed by statutes respecting admissibility of business records; but those statutes do not eliminate the common law rule. The common law rule remains such that a Court, in the circumstances of each case before it, on a flexible basis, may admit evidence of the kind at issue here.
[28] Having reviewed the remaining evidence, I find that it relates to work done in the ordinary course of the duties of the persons recording it, the records were made contemporaneously, and I find no reason to believe that there was falsification or any motive or interest to falsify what was recorded. I hold that the evidence at issue, except as to Senn-Bilfinger, as aforesaid, is admissible.
THE ‘653 PATENT
[29] At issue is Canadian Letters Paten No. 2,139,653 (the ‘653 patent). That patent, entitled “Optically Pure Salts of Pyridinylmethyl Sulfinyl – IH – Benzimidazole Compounds” was issued and granted to AstraZeneca Aktiebolag on July 10, 2007. The application for that patent was filed in the Canadian Patent Office on May 27, 1994, thus the term of the patent, provided all maintenance fees are paid and the patent is not expunged, will expire twenty years from that date, May 27, 2014. The application claims priority from an application filed in Sweden on May 28, 1993. The application was laid open and available to the public (publication date) on December 8, 1994. Per Lindberg and Sverker von Unge, both of Sweden, are named as inventors.
[30] Since the application for the patent was filed with the Canadian Patent Office after October 1, 1989, the “new” provisions of the Patent Act apply to the application and the patent.
[31] The parties have agreed that the “claim date” relevant for the determination of some of the matters put in issue is the priority filing date - May 28, 1993.
THE ISSUES
[32] The overriding issue is whether the allegations made by Apotex in its Notice of Allegation that claim 8 of the ‘653 patent is invalid, are justified within the meaning of section 6(2) of the NOC
Regulations. Some of the allegations made in that respect have been dropped by Apotex. The following allegations remain in contention:
1. Lack of Sound Prediction as to utility;
2. Anticipation having regard to the state of the art and the German application DE ‘455; and
3. Obviousness having regard to the state of the art, DE ‘455 and the Erlandsson article
[33] In order to address these matters, the Court must first address the following:
a) Who is the person skilled in the art to whom the patent is addressed?
b) What was the state of the art at the relevant time?
c) What was the problem that the patent addresses?
d) What is the solution offered to that problem by the patent?
e) What is the proper construction of claim 8?
f) Who bears the burden of proof?
a) Who is the person skilled in the art to whom the patent is addressed?
[34] The ‘653 patent begins with a statement as to the Field of the Invention:
Field of the Invention
The present invention is directed to new compounds with high optical purity, their use in medicine, a process for their preparation and their use in the manufacture of pharmaceutical preparation. The invention also relates to novel intermediates in the preparation of the compounds of the invention.
[35] In the Background discussion that follows, it is stated that the patent deals with omeprazole; and more particularly, one of its enantiomers, esomeprazole, all of which is part of the prior art. The patent thereafter states that it deals particularly with an improved process for making very pure esomeprasole, and very pure esomeprazole itself.
[36] Each of the parties provided, through a number of expert witnesses, opinions as to a proper characterization of the person to whom the patent is addressed - the person of ordinary skill in the art (POSITA). For Apotex, representative of what its experts say is Dr. Myerson at paragraph 35:
35. Based on the subject matter of the 653 Patent, in my opinion the person of ordinary skill in the art to whom the patent is addressed would include organic and medicinal chemists. Such persons would have a Bachelors, Masters or Ph.D. degree in chemistry, chemical engineering or related fields, with at least a few years of experience in either academics or the chemical or pharmaceutical industry. Such a person would also have a working knowledge of the principles of stereochemistry, analytical techniques for separating enantiomers, salt formation and properties, and
crystals and crystallization. The person of ordinary skill in the art would also include pharmacologists with experience in pharmacokinetics and metabolism.
[37] For AstraZeneca, representative of what its experts say is Dr. Armstrong, at paragraph 103:
E. Person of Ordinary Skill in the Art
103. I have been asked to comment on the education and experience of a skilled person to whom the ‘653 patent is addressed. Based on my reading of the ‘653 patent, the skilled person to whom this patent is addressed would include a person or persons having an M.S. or a B.X. degree in organic, analytical, medicinal or pharmaceutical chemistry, plus 3 to 5 years work experience in techniques relating to separation and purification of organic/pharmaceutical molecules, or having a Ph.D. degree in organic, analytical, medicinal or pharmaceutical chemistry having experience in separation and purification of organic/pharmaceutical molecules.
[38] In cross-examination, particularly in answer to questions 337 to 341 (pages 6317 – 6318 of the Record) Dr. Andersson agreed that such a person would also be involved in pharmakinetics and pharmacology. Therefore, his view of a person of ordinary skill in the art essentially coincides with that of Dr. Myerson, whose definition I accept and adopt as appropriate for a POSITA respecting the ‘653 patent.
[39] I repeat what I wrote in Merck & Co. Inc. v. Pharmascience Inc., May 11, 2010, 2010 FC 510 at paragraphs 38 and 40, respecting a POSITA:
38 In dealing with individual cases, the Court must guard against making too fine a distinction as to identifying the "ideal" POSITA. Counsel for each party will argue meanings and shades of meanings most favourable to their case and the witness(es) they present. Each Counsel will argue that their witness(es) best fit the description of the ideal POSITA while there are numerous shortcomings with each of the witness(es) for the opposing party.
. . .
40 To require fine precision and ranking of voices is to place a series of "trip wires" upon which a Court may be expected to stumble or risk sanctions by a higher Court. There must be some generalized treatment of the question of defining a POSITA and a level of generalization applied.
b) What was the state of the art at the relevant time?
[40] In this regard, one may start with what the ‘653 patent says that the state of the art was. Statements made in a patent as to the state of the art are binding on the patentee (Whirlpool Corp. v. Camco Inc. (1997), 76 C.P.R. (3rd) 150 at page 186 (F.C.) aff’d (1999), 85 C.P.R. (3rd) 129 (F.C.A.) and [2000] 2 S.C.R. 1067; Shire Biochem Inc. v. Canada (Minister of Health) (2008), 67 C.P.R. (4th 94 at para. 24 (F.C.A.).
[41] At page 1, following the title “Background of the Invention”, the ‘653 patent acknowledges that the following is part of the state of the art preceding the making of the alleged invention:
· Omeprazole and its salts is a known compound:
The compound 5-methoxy-2-[[(4-methoxy-3.5-dimethyl-2-pyridinl)methyl]sulfinyl]-1H-bensimidazole, having the generic name omeprazole, and therapeutically acceptable alkaline salts thereof are described in EP 5129 and EP 124 495, respectively.
· Omeprazole has a known use; it is effective in dealing with gastric acids and ulcers:
Omeprazole and its alkaline salts are effective gastric acid secretion innibitors, and are useful as antiulcer agents
· Omeprazole can exist as two optical isomers (enantiomers):
The compounds,being sultoxides, have an asymmetric center in the sulfer atom, i.e. exist as two optical isomers (enantiomers)
· The Erlandsson article previously referred to describes the resolution of the enantiomers of omeprazole on an analytical scale, and DE ‘455 previously referred to describes the same in a preparative scale. (These are the two pieces of prior art principally relied upon by Apotex):
The separation of the enantiomers of omeprazole in analytical scale is descried in e.g. J. Chromatography, 532 (1990), 305-19(Erlandsson) and in a preparative scale in DE 4035455.
· DE ‘455 has disadvantages, being devastating localized pH values and heat generation, which is difficult to handle in large scale production:
The latter has been done by using a diastereomeric ether which is separated and thereafter hydrolysed in an acidic solution. Under the acidic conditions needed for hydrolysis of the attached group, omeprazole is quite sensitive and the acid has to be quickly neutralized with a base to avoid degradation of the acid-sensitive compound. In the above mentioned application this is done by adding the reaction mixture containing concentrated sulphuric acid to a concentrated solution of NaOH. This is disadvantageous because there is a great risk of locally reaching pH values between 1-6 which would be devastating for the substance. Moreover, instantaneous neutralisation will create heat which will be difficult to handle in large scale production.
[42] During the course of argument at the hearing of this matter, AstraZeneca’s counsel made reference to paragraph 16 of the affidavit of Dr. Mayersohn, one of Apotex’s experts (page 5798 of the Record). In response to my question, counsel said that he agreed with the summary presented there:
16. The ‘653 patent describes particular base addition salts of the enantiomers of omeprazole, their preparation, and their use as proton pump inhibitors of the generation of stomach acid. The ‘653 patent also cites references for the separation of the enantiomers on both analytical and preparative scales. Skilled persons reading the ‘653 patent already were aware that omeprazole and its two individual enantiomers were proton pump inhibitors.
[43] AstraZeneca, in argument, put forward a portion of Dr. Caldwell’s affidavit, an Apotex expert, and agreed with that portion as far as it went. I refer to paragraphs 114 and 115 (Record, page 5616), noting that the acronym PPI stands for “proton pump inhibitor”, the proton pump being that which is found in the stomach that produces acid:
114. Omeprazole was a blockbuster PPI – By May 1993, it was commonknowledge that omeprazole was a very successful drug that was useful to treat conditions that required the inhibition of gastric acid secretion in humans. This fact was described inmany sources available to skilled persons including Lindberg et. al., “Omeprazole: The first Proton Pump Inhibitor.”
115. Skilled persons were motivated to resolve omeprazole to its enantiomers and study their respective properties – Omep