Amgen Canada Inc. v. Apotex Inc.

Amgen Canada Inc. v. Apotex Inc.
Court (s) Database
Federal Court Decisions
Date
2015-11-10
Neutral citation
2015 FC 1261
File numbers
T-2072-12
Decision Content
Date: 20151110
Docket: T-2072-12
Citation: 2015 FC 1261
Toronto, Ontario, November 10, 2015
PRESENT: The Honourable Mr. Justice Hughes
BETWEEN:
AMGEN CANADA INC. AND AMGEN INC.
Applicants
and
APOTEX INC. AND
THE MINISTER OF HEALTH
Respondents
JUDGMENT AND REASONS
[1] This is an application brought under the provisions of the Patent Medicines (Notice of Compliance) Regulations, SOR/93-133, as amended, (“NOC Regulations”). The Applicants are seeking to restrain the Respondent, The Minister of Health (“Minister”) from issuing a Notice of Compliance to the Respondent, Apotex Inc., in respect of its proposed filgrastim single-use, pre-filled syringes for parenteral administration in 300 μg/0.5 mL and 480 μg/0.5 mL strengths (“Apotex Product”) until the expiry of Canadian Letters Patent No. 1,341,537 (‘537 patent).
[2] For the Reasons that follow, Amgen has not satisfied me that Apotex’s allegation that Claim 43 of the ‘537 patent is invalid for obviousness is not justified. Therefore, the application for prohibition will be dismissed.
[3] The following is an Index to the topics covered in these Reasons, by paragraph number:
TOPIC
PARAGRAPH NO.
PARTIES AND BACKGROUND
4
THE EVIDENCE
9
WHAT DID AMGEN DO
16
PATENT AT ISSUE
28
ISSUES
36
BURDEN
40
PERSONS OF ORDINARY SKILL IN THE ART (POSITA)
42
THE ‘537 PATENT IN DETAIL
47
CLAIM 43
53
CONSTRUCTION OF CLAIM 43
54
ANTICIPATION (NOVELTY)
62
OBVIOUSNESS
81
UTILITY – PROMISE OF PATENT
108
CONCLUSIONS AND COSTS
122
I. PARTIES AND BACKGROUND [4] The Applicant, Amgen Canada Inc., has listed the ‘537 patent on a list kept by the Minister under the provisions of the NOC Regulations. As such, Amgen Canada is referred to in those regulations as a “first person”. Amgen Canada has already secured a Notice of Compliance from the Minister in respect of a product it calls Neupogen which is a sterile solution containing a drug known as filgrastim in 300 μg/mL and 600 μg/mL strength for subcutaneous or intravenous administration.
[5] The other Applicant, Amgen Inc., is the owner of the ‘537 patent. Unless otherwise stated, I will refer to the Applicants collectively as Amgen.
[6] The Respondent, Apotex Inc., is a Canadian drug company generally referred to as a generic, and referred to in the NOC Regulations as a “second person”. It has applied to the Minister for a Notice of Compliance to sell the Apotex Product which is a generic version of the Amgen Neupogen product. The NOC Regulations require that Apotex serve Amgen a Notice of Allegation respecting the ‘537 patent, which it did by letter dated October 2, 2012. Apotex alleged that it would not infringe that patent and that the patent is invalid for a variety of reasons as set out in that Notice.
[7] Amgen, having received Apotex’s Notice of Allegation, commenced these proceedings by filing a Notice of Application on November 16, 2012. While the NOC Regulations provide that, ordinarily, the Court must issue an Order within two years of that filing date, that period has been extended by an Order of this Court dated October 7, 2013 to sixty (60) days from the end of the hearing of this application. The hearing ended on October 30, 2015.
[8] The Minister, while served with the relevant papers, took no active part in this proceeding.
II. THE EVIDENCE [9] As is usual in proceedings of this kind, evidence took the form of affidavits and transcripts of the cross-examinations with exhibits as identified therein. A Confidentiality Order was made but, at the hearing, the parties waived any claim to confidentiality.
A. Amgen’s Fact Witnesses [10] Amgen filed the affidavits of six persons who testified as to the developments at Amgen leading to the patent at issue. Each of them, except Ms. Fare, was cross-examined. They are:
Thomas Boone, sworn March 12, 2013. He was Vice President of Protein Sciences at Amgen before retiring in 2009. He currently consults for several companies including Amgen. He was involved in the development of filgrastim as a Research Associate working under the supervision of the named inventor, Dr. Larry Souza, and gives evidence on the research and development that took place. He discusses the development of filgrastim, and reviews protein synthesis, transcription and translation, and methods of gene sequencing.
• (Dr.) Arthur M. Cohen, sworn March 8, 2013. He is a retired Amgen employee, having left in 2001 holding the title of Director of the Pharmacology Group. During the development of filgrastim, he held the title of Research Scientist and worked as a pharmacologist conducting in vivo studies. He has provided evidence on the in vivo studies conducted using filgrastim in hamsters. He discusses in vivo testing methodologies including lab tests performed on the animals.
• Joan A. Fare (Brezewski), sworn March 8, 2013. She is a retired Amgen employee, having left the company in 2001 holding the title of Associate Director with the Compliance Group. She was involved in the development of filgrastim as a Research Associate. She did not report directly to the named inventor, but assisted him in culturing a cell line and took direction from him while doing so. Her evidence relates to the culturing of cells as part of the development of filgrastim.
• (Dr.) Hsieng Lu, sworn March 7, 2013. She is a biochemist currently working at Amgen in the protein sequencing group. She began working at Amgen in 1984, part-way through the development process. She provides evidence on the protein sequencing aspect of that process.
• Stuart L. Watt, sworn March 12, 2013. He is a Vice President of Law and the Intellectual Property Officer at Amgen. He gives evidence respecting the ‘537 patent and the US patents for which a priority claim is made. He explains circumstances as to why two individuals (Dr. Lawrence Souza, the named inventor, and Dr. Janice Gabrilove, a scientist at the Sloan-Kenning Institute involved in the development of filgrastim) have not submitted affidavit evidence. He attests to several awards won by Amgen for filgrastim.
• (Dr.) Krisztina M. Zsebo, sworn March 12, 2013. She is a biochemist and Chief Executive Officer and Director of Celladon Corporation. She had worked as a research scientist at Amgen from 1984 to 1992. She testifies as to her involvement in the development of filgrastim including the production of culture medium, in vitro testing, in vivo testing, and helping express a mammalian version (as opposed to the E. coli version) of the protein.
B. Amgen’s Expert Witnesses [11] Amgen filed the affidavits of five persons as experts, each of whom was cross-examined. No challenge was raised as to their claimed expertise. They are:
• (Dr.) Connie Eaves, sworn September 24, 2014. She is a Distinguished Scientist in the Terry Fox Laboratory, part of the British Columbia Cancer Agency. She is an independent researcher and has been involved in studies involving filgrastim. She claims to be an expert in haematopoietic research (research about how blood cells are generated and differentiate). Her evidence relates to who the person of ordinary skill in the art (POSITA) is, what the state of the art was in 1985, what the patent promises, whether the patent was useful, and explains some terms including “pluripotent”.
• Randolph Wall, sworn September 29, 2014. He is a Distinguished Professor of Microbiology, Immunology and Molecular Genetics at the Molecular Biology Institute, University of California Los Angeles (UCLA) and the David Geffen School of Medicine at UCLA. He is also an Associate Director of the Broad Center of Regenerative Medicine and Stem Cell Research at UCLA. He claims expertise in molecular biology, genetics, immunology and cancer. He provides relevant scientific background information, information about the POSITA including their common general knowledge, the inventive concept of the ‘537 patent, and he speaks to anticipation and obviousness.
• (Dr.) Ross MacGillivray, sworn September 29, 2014. He is a Professor of Biochemistry & Molecular Biology in the Faculty of Medicine at the University of British Columbia (UBC), as well as a researcher at the UBC Centre for Blood Research. He claims expertise in blood clotting factors and blood proteins. He provides evidence relating to who the POSITA is; what Claim 43 of the ‘537 patent covers; when the research team had completed the necessary steps to make the invention; whether the US patent based on which they are claiming priority is for the same invention; and whether the invention was enabled, obvious, double patenting, or void under s. 53, as alleged by Apotex.
• (Dr.) Hans A Messner, sworn September 24, 2014. He is a Professor of Medicine at the University of Toronto and staff physician at the Princess Margaret Cancer Centre. He claims expertise in haematopoiesis and stem cell transplantation. He provides background information on haematopoiesis and scientific tests used to study haematopoiesis. He also provides an opinion on the promised utility of the ‘537 patent, including how the POSITA would have interpreted certain terms in the mid-1980’s, whether utility was demonstrated or soundly predicted, and current clinical indications and utility of filgrastim.
• David W. Speicher, sworn September 29, 2014. He is the Caspar Wistar Professor of Computational and Systems Biology, the Director of the Proteomics/Mass Spectrometry Facility, and the Co-chair of the Molecular & Cellular Oncogenesis Program, and the Director of the Center for Systems and Computational Biology at the Wistar Institute in Philadelphia. He claims to be an expert in protein chemistry and sequencing. He provides evidence on allegations of obviousness, the POSITA, and what Example 1 in the ‘537 patent describes and whether it would have been obvious to the POSITA.
[12] Amgen also filed two affidavits of a law clerk, Diane Zimmerman, which served to make of record a number of documents. She was not cross-examined.
C. Apotex’s Witnesses [13] Apotex filed the affidavits of four persons as experts, each of whom was cross-examined. No challenge was raised as to their claimed expertise. They are:
• (Dr.) Norman Iscove, sworn August 22, 2013. He is a Senior Scientist at the McEwen Centre for Regenerative Medicine, a Scientist at the Program for Regenerative Medicine at the McLaughlin Centre for Molecular Medicine, and a Senior Scientist at the Ontario Cancer Institute, all located in Toronto. He claims expertise in genetics, molecular biology, experimental hematology and stem cells. His evidence relates to defining the POSITA, what the POSITA would understand the ‘537 patent to teach, and whether this invention was useful or soundly predicted on August 25, 1986. He also comments on cell culture work and colony forming assays in response to some of Amgen’s evidence. He was asked to compare the ‘537 Patent with the US Patents from which it claims priority, to provide general scientific background, and to comment on the motivation of the POSITA to obtain the claimed invention at the priority dates.
• (Dr.) James L. Manley, sworn August 15, 2013. He is the Julian Clarence Levi Professor of Life Sciences in the Department of Biological Sciences at Columbia University. His research is focused on mechanisms and regulation of gene expression in mammalian cells. His evidence relates to the state of the art and the interest in producing recombinant human proteins on August 23, 1985 and March 3, 1986, determining who the POSITA is, what the POSITA would understand the ‘537 patent to claim and what the inventive concepts are, whether ingenuity would have been required of the POSITA at various points in time and with or without materials from Sloan-Kettering, and whether disclosure existed and if that disclosure enabled one to make use of the invention.
• William Stratton Lane, sworn August 14, 2013. He is the Manager of the Harvard University Mass Spectrometry & Proteomics Resource Laboratory. He claims to be an expert in proteomics (the study of proteins, in particular their structure and function). He provides evidence on the state of the art related to, and interest in sequencing purified natural proteins on August 23, 1985 and March 3, 1986. He was asked who the POSITA would be, what the subject matter of the ‘537 patent would be understood to have been, and whether inventive ingenuity would have been required. He also comments on some of Amgen’s evidence.
(Dr.) Robert S. Negrin, sworn May 12, 2015. He is a haematologist and Professor of Medicine (Blood and Marrow Transplantation) at the Stanford University School of Medicine. He claims to be an expert in hematopoiesis, hematopoietic growth factors, and the treatment of blood disorders including some cancers. He was asked who the POSITA would be, what they would have understood the subject matter of the ‘537 patent to be on its publication date (July 31, 2007), and whether the ‘537 patent asserted that the polypeptides would be useful in some way. He discusses how the POSITA would have read two other Canadian Patents (Nos.1,297,004 and 1,297,005), and whether the inventive concepts were the same as in the ‘537 patent. These answers were all provided to counsel by phone. He read the affidavit of Dr. Carl Anthony who was unable to testify in this proceeding due to illness, and adopted Dr. Anthony’s opinions as his own.
[14] In addition, Apotex filed the affidavit of Samira Ali, an investigator employed by Canpro King-Reed LP, operating as CKR Global Investigations. She testifies to unsuccessful attempts to contact or to convince certain individuals, including Dr. Gabrilove, to testify. She was not cross-examined.
[15] Each of Amgen and Apotex criticised some of the expert evidence of the other on various grounds such as undue participation by lawyers in the preparation of the affidavits or failure to direct the evidence to the “real” issues and so forth. These proceedings are intended to be summary but, in reality, are anything but summary. They are, at best, summary trials or mini-trials wherein the Court is asked to consider and rule upon complex scientific matters, decide upon opposing views of sophisticated experts, and deal with complex issues of law, often within a limited timeframe. Something has to be done about this before the system breaks down completely. Given that the Court has not seen any witness in person, it is unfair to ask the Court to make findings as to the propriety of a witness’s conduct or the candor of a witness’s evidence. I will not make any rulings as to the propriety of any witness or their evidence. My decision is based on the evidence itself as I see it in the Record.
III. WHAT DID AMGEN DO [16] I am satisfied that the ‘537 patent fairly sets forth the steps taken by the Amgen inventor, Dr. Souza, and those working under him, to accomplish what they set out to do. The goal was to take the “naturally occurring” protein reported by Dr. Karl Welte at Sloan-Kettering Institute (“SKI”) and to create, by recombinant means, a protein having some or all of the amino acid sequence and some or all of the biological properties of that protein so as to have available, in sufficient quantities, a recombinant protein which showed promise for further research.
[17] As stated at pages 2 and 3 of the patent, a culture medium of a human bladder carcinoma cell line called 5637 had been deposited by another party, presumably SKI, in a Culture Collection in Maryland. As noted in pages 3 and 5, certain restrictions against commercial use appear to apply in respect of access to that culture. The record does not clearly state what those restrictions are.
[18] Welte at SKI had purified from this culture a protein he called pluripotent hematopoietic colony-stimulating factor or pluripotent CSF yielding certain samples in purity ranging from 85% to 95% (patent page 10) which were provided to Amgen. There is no evidence that Welte or anyone else at SKI had determined any of the amino acid sequence. Welte’s paper suggests that some sequencing had been initiated but does not report it. The paper reports a variety of biological characteristics of the protein including a molecular weight of 18,000 daltons.
[19] The ‘537 patent, at pages 10 and 11, Tables I and II, reports that Amgen endeavoured to determine the amino acid sequence using 3-4 μg and 5-6 μg of samples of Welte’s material. In the first instance, Table I, just over ten amino acids were sequenced. In the second instance, Table II, almost 20 amino acids were identified with a few more possibly identified. There was a third run using Welte’s material which yielded no data.
[20] Because these results did not provide a sufficiently long, unambiguous sequence, Amgen undertook to make and purify its own material starting with cells from the 5637 line. This process is set out at pages 11 to 15 of the patent. Material of 85 ± 5% purity was thereby obtained in a quantity of 150-300 μg. Samples of this material were subjected to amino acid sequencing in Run # 4 and #5. Run #4 resulted in 31 amino acids being identified (also referred to as called or sequenced) and Run #5, in 44 acids being identified with a further three potentially identified (Tables III and IV).
[21] Amgen wanted to identify the DNA which was producing the protein of interest. It knew that it was produced by a gene (consisting of a DNA sequence) found in the host cell but not which one. Amgen created artificial DNA which is referred to as cDNA by a process called reverse transcription of mRNA. That process needs not be discussed here. Several different kinds of cDNA were assembled in “libraries”. The goal was to try to locate the particular cDNA coding for the protein of interest within the many candidates found in the libraries. Amgen accomplished this by looking at the 40 or so amino acids identified in the protein sample (Table IV of the patent) and fixing upon a length of ten or so amino acids within that strand from which a “probe” could be created. The probe was itself a string of molecules called oligonucleotides which would adhere to a portion of the cDNA coding for the identified amino acid sequence of the protein. While the evidence shows that there were two or three apparent places along the 40 or so identified amino acid chain from which a probe might be created, one was selected by Amgen using the amino acids at residues 23-30. To reduce the number of potential probes needed, Amgen used the “inosine” technique recently disclosed by Takahashi and others, as set out at pages 17 and 18 of the patent.
[22] By using the probes, several potential cDNA candidates were selected from the cDNA libraries. Those candidates were examined and the most suitable candidate was analysed and sequenced. These processes are described at pages 15 to 33 of the patent.
[23] Example 6 illustrates the assembly of various pieces of genetic material so as to produce the gene that makes the protein in question.
[24] Example 7 illustrates how the gene is then replicated (expressed) in a bacteria (E. coli) medium so as to provide the desired protein in quantity. Example 9 does the same in a COS (monkey kidney derivative) medium.
[25] Example 10 illustrates the steps taken to compare several of the biological properties of the resultant protein with those of the naturally occurring protein obtained by Welte. Comparison is made in respect of molecular weight, thymidine uptake, WEHI differentiation, bone marrow cell differentiation, cell binding assays, immunoassay, serine analog bioassays, and an in vivo bioassay.
[26] Thus, the steps taken and tests done show that the protein produced from the recombinant DNA has some or all of the amino acid sequence of the natural: the first 40 are the same and, given the strong resemblance in the bioassay tests and the method by which it was made, it is inferred that the remainder are the same or nearly the same. The recombinant product has the same or nearly the same biological characteristics as the natural.
[27] The evidence adduced by Amgen from the witnesses Boone, Cohen, Fare, and Lu, all of whom participated in this work at Amgen, clearly identifies and confirms that Amgen did the work as set out in the patent. Apotex argued that Amgen did not provide an affidavit from the inventor, Dr. Souza, or from persons working at SKI such as Dr. Gabrilove. I do not find that such evidence was essential. If Apotex wanted the evidence of these persons, there are means, such as letters rogatory, to obtain it. Apotex made no effort in that regard.
IV. PATENT AT ISSUE [28] At issue is Canadian Letters Patent No. 1341537 (the ‘537 patent).
[29] The ‘537 patent is entitled “Production of Pluripotent Granulocyte Colony – Stimulating Factor”. It names Lawrence M. Souza of the United States as the inventor, and was issued and granted to Kirin-Amgen, Inc. of the United States on July 31, 2007.
[30] This patent is somewhat unusual in that it is one of the last to issue under the “old” pre-October 1, 1989 regime. All patent applications filed subsequent to that date fall under the provisions of the “new” Patent Act, RSC 1985 c. P-4, regime. The citation of the Patent Act remains the same; one must look at the date that the application for the patent was filed in the Canadian Patent Office to determine if the patent at issue falls under the “old” or the “new” regime. The application for the ‘537 patent was filed in the Canadian Patent Office on August 25, 1986, thus it is governed by the terms of the “old”, pre-October 1, 1989, Patent Act.
[31] Among the matters governed differently by the “old” Patent Act is the term of the patent, which is seventeen (17) years from the date of grant. The ‘537 patent was granted on July 31, 2007, thus its term will expire on July 31, 2024. The application remained in the Patent Office almost twenty-one (21) years, an unusually long time.
[32] Novelty (anticipation) of an “old” Act patent is to be determined as of two years before the Canadian filing date in dealing with publications and public use. The filing date of the ‘537 patent was August 31, 1985, thus novelty is to be determined as of August 31, 1983. If the allegation is that someone else knew or used the invention before the inventor named in the patent did so, then that other person must have made a public disclosure or use of that invention before the application date of the patent (see sections 27(a) and 61(1)(a) of the “old” Patent Act). Here, the allegation is that persons at the Sloan-Kettering Institute and others in Australia, had such prior knowledge and published their knowledge in scientific journals in papers called “Welte” and “Nicola”.
[33] Obviousness of an “old” Act patent is to be determined as of the “date of the invention”. The date of invention of the ‘537 patent is presumptively taken to be the Canadian filing date, August 25, 1986. That date can be established at an earlier date with reference to foreign priority applications if the substance of the description is essentially the same as the Canadian patent. Here, two United States patent applications were named as priority applications; United States Application No. 768,959, filed August 23, 1985, and United States Application No. 835,548, filed March 3, 1986. An even earlier date of invention can be proven upon evidence before the Court. In the present case, Amgen relied upon the earlier of two priority filing dates, namely August 23, 1985, and Apotex was apparently content to deal with obviousness as of that date.
[34] The patent is to be read, through the eyes of a person skilled in the art (POSITA or PSA), as of the date it was first made public. Under the “old” Patent Act, a patent application is never made public so that the public first sees the patent is the day that it is issued and granted. Here, that date is July 31, 2007; see Whirlpool Corp. v Camco Inc., [2000] 2 SCR 1067 at para. 55 and Free World Trust v Électro Santé Inc., [2000] 2 SCR 1024 at para. 54. Amgen raised the question as to whether the patent was to be read as of the date of grant but through the eyes of a POSITA who was aware that the patent description had been written in 1985, and thus used the language of that date. This question, though intriguing, was not required to be pursued in the context of the issues raised at the hearing.
[35] Whether the patent is an “old” or “new” Patent Act patent, it is initially presumed to be valid.
V. ISSUES [36] The fundamental issue before the Court is whether an Order should be given prohibiting the Minister from issuing a Notice of Compliance to Apotex in respect of the Apotex Product at issue. In this regard, the Court must determine whether the allegations made by Apotex in its Notice of Allegations are “justified”.
[37] Apotex made numerous allegations in its Notice of Allegations. Those allegations made by Apotex, and the issues raised by Amgen in its Notice of Application, have been substantially reduced. Only Claim 43 of the ‘537 patent is now at issue. Only validity is at issue, not infringement. As to validity, the following four issues were stated in Apotex’s Memorandum:
• Novelty
• Overbreadth
• Obviousness
• Inutility
[38] At the hearing, Apotex’s Counsel withdrew the “Overbreadth” issue, leaving only three issues as to invalidity to be dealt with by this Court: Novelty, Obviousness and Inutility.
[39] Therefore, the Court will consider only the three remaining validity issues as set out above.
VI. BURDEN [40] The remaining issues all relate to Apotex’s allegations that the ‘537 patent is invalid. Apotex is constrained by its Notice of Allegation such that it cannot raise new grounds of invalidity (e.g. Pfizer Canada Inc. v Canada (Minister of Health), 2006 FC 1471 at paragraphs 70 to 72); however, it can, as it has done here, restrict its arguments as to invalidity to fewer than those raised in the Notice of Allegation.
[41] The ultimate burden rests on Amgen to satisfy the Court that the allegations as to invalidity put in play by Apotex are not justified (NOC Regulations, s. 6(2)). That burden is initially satisfied by the presumption of validity afforded by the “old” Patent Act, s. 45. However, once evidence as to invalidity is led, as is the case here, the Court must consider the matter based on the evidence. The first party, Amgen, at this point, bears the burden of proving on the evidence that the allegations are not justified (e.g. Pfizer Canada Inc. v Apotex Inc., 2007 FC 26 at paragraphs 5 to 13; aff’d 2007 FCA 195). I repeat what I wrote in Allergan Inc. v Canada (Minister of Health), 2012 FC 767 at paragraph 42:
[42] As to the allegations of invalidity, the Patent Act, RSC 1985, P-4, section 43(2) affords a presumption of validity; however, once a second person, here Apotex, puts in some evidence as to invalidity, the Court must determine the matter on the usual civil burden; namely, balance of probabilities. I repeat what I wrote in GlaxoSmithKline Inc v Pharmascience Inc, 2011 FC 239 at paras 43 and 44:
43 O'Reilly J of this Court has summarized the question of burden of proof where the issue is invalidity in Pfizer Canada Inc. v. Apotex Inc., 2007 FC 26, 59 CPR (4th) 183 (aff'd 2007 FCA 195, leave to appeal refused [2007] SCCA No. 371) at paragraphs 9 and 12:
9 In my view, the burden on a respondent under the Regulations is an "evidential burden" -- a burden merely to adduce evidence of invalidity. Once it has discharged this burden, the presumption of validity dissolves and the Court must then determine whether the applicant has discharged its legal burden of proof. I believe this is what is meant in those cases where the Court has stated that the respondent must put its allegations "into play". It must present sufficient evidence to give its allegations of invalidity an air of reality.
...
12 To summarize, Pfizer bears the legal burden of proving on a balance of probabilities that Apotex's allegations of invalidity are unjustified. Apotex merely has an evidentiary burden to put its case "into play" by presenting sufficient evidence to give its allegations of invalidity an air of reality. If it meets that burden, then it has rebutted the presumption of validity. I must then determine whether Pfizer has established that Apotex's allegations of invalidity are unjustified. If Apotex does not meet its evidential burden, then Pfizer can simply rely on the presumption of validity to obtain its prohibition order.
44 In Pfizer Canada Inc. v. Canada (Minister of Health), 2008 FC 11, 69 C.P.R. (4th) 191, I said in respect of the same thing at paragraph 32:
32 I do not view the reasoning of the two panels of the Federal Court of Appeal to be in substantial disagreement. Justice Mosley of this Court reconciled these decisions in his Reasons in Pfizer Canada Inc. v. Apotex Inc., [2007] F.C.J. No. 1271, 2007 FC 971 at paragraphs 44 to 51. What is required, when issues of validity of a patent are raised:
1. The second person, in its Notice of Allegation may raise one or more grounds for alleging invalidity;
2. The first person may in its Notice of Application filed with the Court join issue on any one or more of those grounds;
3. The second person may lead evidence in the Court proceeding to support the grounds upon which issue has been joined;
4. The first person may, at its peril, rely simply upon or, more prudently, adduce its own evidence as to the grounds of invalidity put in issue.
5. The Court will weigh the evidence; if the first person relies only on the presumption, the Court will the presumption of validity afforded by the Patent Act nonetheless weigh the strength of the evidence led by the second person. If that evidence is weak or irrelevant the presumption will prevail. If both parties lead evidence, the Court will weigh all the evidence and determine the matter on the usual civil balance.
6. If the evidence weighed in step 5 is evenly balanced (a rare event), the Applicant (first person) will have failed to prove that the allegation of invalidity is not justified and will not be entitled to the Order of prohibition that it seeks.
VII. PERSONS OF ORDINARY SKILL IN THE ART (POSITA) [42] The characterization of the Person of Ordinary Skill in the Art (“POSITA”), sometimes shortened to Person Skilled in the Art (“PSA”) is to be defined by the Court. This is the person to whom the patent is said to be addressed, through whose eyes the Court is to read the patent, and who stands as the criterion for determination of obviousness.
[43] Amgen describes the POSITA at paragraph 47 of its Memorandum as follows:
Both parties' experts essentially agree that the person of ordinary skill would likely comprise a team of people with expertise in biochemistry, molecular biology and hematology. However, there is considerable disagreement about the extent of the expertise and equipment that the people comprising this team would have (or have access to). Apotex attempts to raise the level of skill to one that makes the pioneering work of the Souza group seem commonplace. In particular, in the mid-1980s, essentially all molecular cloning had been accomplished in very few highly expert laboratories, with the latest equipment and expertise. While Apotex's argument boils down to, "molecular cloning of cytokines had been accomplished by others" this had been accomplished by the leaders of the field, and not persons of ordinary skill.
[44] Apotex describes the POSITA at paragraph 14 of its Memorandum as follows:
There is no significant dispute regarding the attributes of the skilled addressee of the 537 patent. The subject matter of the 537 patent includes hematopoietic growth factor proteins, the purification of such proteins, DNA sequences coding for such proteins, recombinant techniques to produce such proteins and pharmaceutical compositions containing such proteins and thus the skilled addressee is competent in these areas. The 537 patent is addressed to a team of persons with advanced degrees and several years of experience in disciplines such as molecular biology, biochemistry, protein chemistry, amino acid sequencing and hematology.
[45] Thus, both parties are agreed that the POSITA is a team of persons with expertise in biochemistry, molecular biology and hematology. The length of time that such a team has been engaged in these fields and the level of expertise is somewhat in dispute. One must remember that a POSITA is a person of ordinary skill in the art, not the newcomer, not the greatest of experts, but an ordinary person in the field at issue. The matter was well stated by Justice Phelan in Merck-Frosst-Schering Pharma GP v. Canada (Minister of Health), 2010 FC 933 at paragraph 69:
69. It must be remembered that the POSITA is a person of skill in the art so the degree of separation between the right and left hemisphere must reflect the characteristics of the notional POSITA. The person is neither first nor last in her class but somewhere in the middle.
[46] I accept Apotex’s definition of a POSITA as being more consistent with that postulated in our jurisprudence. Amgen pitches it too high when it urges that a POSITA must be a team of persons in highly expert laboratories.
VIII. THE ‘537 PATENT IN DETAIL [47] The ‘537 patent is a lengthy document. It begins at page 1 with a general description of the invention:
The present invention pertains in general to hematopoietic growth factors and to polynucleotides encoding such factors. The present application pertains in particular to mammalian pluripotent colony stimulating factors, specifically human pluripotent granulocyte colony-stimulating factor (hpG-CSF), to fragments and polypeptide analogs thereof and to polynucleotides encoding the same.
[48] There follows a discussion of the human blood-forming hematopoietic system with a focus on a factor the patent calls human pluripotent granulocyte colony-stimulating factor (hpG-CSF). The characterization of this factor and recombinant production of this factor in commercial scale quantities is what the invention is directed to. Simply extracting that factor from cell cultures is inadequate. At pages 4 and 5, the patent says, in part:
Based upon their common properties, it appears that human CSF-B of Nicola, et al., supra, and the hpCSF of Welte, et al., supra, are the same factor which could properly be referred to as a human pluripotent granulocyte colony-stimulating factor (hpG-CSF). Characterization and recombinant production of hpG-CSF would be particularly desirable in view of the reported ability of murine G-CSF to completely suppress an in vitro WEHI-30 3B D+ leukemic cell population at "quite normal concentrations", and the reported ability of crude, injected preparations of murine G-CSF to suppress established transplanted myeloid leukemias in mice. Metcalf, Science, 229, 16-22 (1985). See also, Sachs, Scientific American, 284(1), 40-47 (1986).
To the extent that hpG-CSF may prove to be therapeutically significant and hence need to be available in commercial scale quantities, isolation from cell cultures is unlikely to provide an adequate source of material. It is noteworthy, for example, that restrictions appear to exist against commercial use of Human Tumor Bank cells such as the human bladder carcinoma cell line 5637 (A.T.C.C. HTB9) which have been reported as sources of natural hpCSF isolates in Welte, et al. (1985, supra).
[49] A summary of the invention is set out at pages 5 to 8 which states, in part:
Summary of the Invention
According to the present invention, DNA sequences coding for all or part of hpG-CSF are provided. Such sequences may include: the incorporation of codons "preferred" for expression by selected non-mammalian hosts; the provision of sites for cleavage by restriction endonuclease ,enzymes and the provision of additional initial, terminal or intermediate DNA sequences which facilitate construction of readily expressed vectors. The present invention also provides DNA sequences coding for microbial expression of polypeptide analogs or derivatives of hpG-CSF which differ from naturally-occurring forms in terms of the identity or location of one or more amino acid residues (i.e., deletion analogs containing less than all of the residues specified for hpG-CSF; substitution analogs, such as (ser17] hpG-CSF, wherein one or more residues specified are replaced by other residues; and addition analogs wherein one or more amino acid residues is added to a terminal or medial portion of the polypeptide) and which share some or all the properties of naturally-occurring forms.
…
The present invention provides purified and isolated polypeptide products having part or all of the primary structural conformation (i.e., continuous sequence of amino acid residues) and one or more of the biological properties (e.g, immunological properties and in vitro biological activity) and physical properties (e.g., molecular weight) of naturally-occurring hpG-CSF including allelic variants thereof. These polypeptides are also characterized by being the product of chemical synthetic procedures or of procaryotic or eukaryotic host expression (e.g., by bacterial, yeast, higher plant, insect and mammalian cells in culture) of exogenous DNA sequences obtained by genomic or cDNA cloning or by gene synthesis. The products of typical yeast (e.g., Saccaromyces cerevisiae) or procaryote [e.g., Escherichia coli (E. coli)] host cells are free of association with any mammalian proteins. The products of microbial expression in vertebrate (e.g., non-human mammalian and avian) cells are free of association with any human proteins. Depending upon the host employed, polypeptides of the invention may be glycosylated with mammalian or other eucaryotic carbohydrates or may be non-glycosylated. Polypeptides of the invention may also include an initial methionine amino acid residue (at position -1).
Also comprehended by the invention are pharmaceutical compositions comprising effective amounts of polypeptide products 9f the invention together with suitable diluents, adjuvants and/or carriers useful in hpG-CSF therapy.
[50] Some possibilities for the invention are set out at page 8:
Polypeptide products of the present invention may be useful, alone or in combination with other hematopoietic factors or drugs in the treatment of hematopoietic disorders, such as aplastic anemia. They may also be useful in the treatment of hematopoietic deficits arising from chemotherapy or from radiation therapy. The success of bone marrow transplantation, for example, may be enhanced by application of hpG-CSF. Wound healing burn treatment and the treatment of bacterial inflammation may also benefit from the application of hpG-CSF. In addition, hpG-CSF may also be useful in the treatment of leukemia based upon a reported ability to differentiate leukemic cells. Welte, et al., Proc. Natl. Acad. Sci. (USA), 82, 1526-1530 (1985) and Sachs, supra.
[51] A Detailed Description follows with a number of Examples described in general at page 9:
The following examples are presented by way of illustration of the invention and are specifically directed to procedures carried out· prior to identification of hpG-CSF cDNA and genomic clones, to procedures resulting in such identification, and to the sequencing, development of expression systems based on cDNA, genomic and manufactured genes and verification of expression hpG-CSF and analog products in such systems.
More particularly, Example 1 is directed to amino acid sequencing of hpG-CSF. Example 2 is directed to the preparation of a cDNA library for colony hybridization screening. Example 3 relates to construction of hybridization probes. Example 4 relates to hybridization screening, identification of positive clones, DNA sequencing of a positive cDNA clone and the generation of polypeptide primary structural co