Bristol-Myers Squibb Canada v. Apotex Inc.

Bristol-Myers Squibb Canada v. Apotex Inc.
Court (s) Database
Federal Court Decisions
Date
2017-03-21
Neutral citation
2017 FC 296
File numbers
T-1100-15
Decision Content
Date: 20170321
Docket: T-1100-15
Citation: 2017 FC 296
Ottawa, Ontario, March 21, 2017
PRESENT: The Honourable Mr. Justice Manson
BETWEEN:
BRISTOL-MYERS SQUIBB CANADA and BRISTOL-MYERS SQUIBB HOLDING IRELAND
Applicants
and
APOTEX INC. AND THE MINISTER OF HEALTH
Respondents
judgment and reasons
I. Introduction and Issues 3
A. Issues 4
B. Burden of Proof 6
C. Results 6
II. Background 7
A. Chronic Myelogenous Leukemia (“CML”) 7
B. Treatment of CML in the early 2000s 8
C. Emergence of resistance to imatinib therapy 9
III. The Applicants’ Expert Witnesses 9
A. Dr. Moshe Talpaz 9
B. Dr. Mark P. Wentland 11
C. Dr. Joel Barrish 11
D. Dr. Francis Lee 12
E. Dr. William L. Jorgensen 12
IV. The Respondent’s Expert Witnesses 13
A. Dr. B. Douglas Smith 13
B. Dr. Thomas E. Smithgall 14
V. The ‘932 Patent 15
A. The Patent 15
B. The Relevant Date 18
C. The Persons of Ordinary Skill in the Art (POSITA) 19
D. Common General Knowledge as of April 15, 1999 20
(1) Preparation and testing of the compounds in the BMS Patents 20
VI. Validity of the ‘932 Patent 21
A. Utility 21
(1) Law 21
(2) Analysis 23
(a) The ‘932 NOA 25
(b) Promise of the Patent 26
(c) Sound Prediction of Utility 32
(3) Conclusion on Utility 35
B. Sufficiency 36
(1) Law 36
(2) Analysis 38
VII. The ‘898 Patent 39
A. The Patent 39
B. The Relevant Date 41
C. POSITA 41
D. Common General Knowledge as of March 23, 2003 41
(1) Src-family PTKs and imatinib-resistant CML 42
(2) Conclusion to common general knowledge 47
E. Prior Art 48
(1) PCT Application No. WO/2000/062778 (the “‘778 Application”) 48
(2) WO 03/013540 (the “‘540 Application”) 50
(3) Donato et al. Blood, 101: 690-698, 2003 51
(4) Stanglmaier et al. Leukemia, 17: 283-290, 2003 51
(5) Golas et al. Cancer Research, 63: 375-381, 2003 52
(6) Warmuth et al. Blood, 101: 664-672, 2003 52
(7) Wilson et al. Oncogene, 21: 8075-8088, 2002 52
VIII. Validity of the ‘898 Patent 53
A. Obviousness 53
(1) Law 53
(2) Analysis 54
(a) Claim 1: Treatment of CML 56
(b) Claim 3: Treatment of imatinib-resistant CML 61
(3) Conclusion Obviousness 66
B. Double Patenting 67
(1) Law 67
(2) Analysis 68
IX. Costs 72
I.
Introduction and Issues
[1] The Applicants in this action are Bristol-Myers Squibb Canada (“BMS-Canada”) and Bristol-Myers Squibb Holdings Ireland (“BMS-Ireland”) (collectively, the “Applicants”). BMS-Canada is a Canadian pharmaceutical manufacturer that distributes and sells, among other things, the pharmaceutical SPRYCEL®. BMS-Canada is a first person as defined in the Patented Medicines (Notice of Compliance) Regulations, SOR/93-133, subsections 2(1) and 4(1) (PM(NOC) Regulations). BMS-Ireland is the owner of Canadian Patent Nos. 2,366,932 (the “‘932 Patent”) and 2,519,898 (the “‘898 Patent”).
[2] For purposes of this application, both the ‘932 and the ‘898 Patents (together the “BMS Patents”) generally relate to the compound dasatinib, and have been listed on the Patent Register with respect to SPRYCEL®, pursuant to section 4 of the PM(NOC) Regulations.
[3] The Respondent, Apotex Inc. (the “Respondent”), is a generic pharmaceutical manufacturer. It filed an Abbreviated New Drug Submission (“ANDS”) with the Minister of Health (the “Minister”) seeking a Notice of Compliance (“NOC”) for APO-Dasatinib, using SPRYCEL® as the Canadian reference product. It served Notices of Allegation (“NOA”) regarding the ‘932 Patent and the ‘898 Patent (the ‘932 NOA and the ‘898 NOA, respectively), on May 26, 2015.
[4] The Applicants commenced this prohibition application on July 2, 2015, seeking orders that the Minister be prohibited from issuing a NOC to Apotex for APO-Dasatinib until after the ‘932 and the‘898 Patents expire.
A. Issues
[5] The issues are characterized in the ‘932 NOA and the ‘898 NOA as follows:
The ‘932 Patent:
Are the claims 1 to 6 and 8 to 43 irrelevant for failing to contain a claim for the medicinal ingredient, the formulation, the dosage form, or an approved use of the medicinal agreement?
Does APO-Dasatinib infringe the ‘932 Patent?
Is the ‘932 Patent invalid because:
the patent specification is insufficient;
the claims are ambiguous;
claims 1, and 7 to 43 are broader than any invention made or disclosed; or
the promised utility of the invention was neither demonstrated nor soundly predicted as of the relevant date?
The ‘898 Patent:
Are claims 2, 4 to 26, and 28 irrelevant for failing to relate to a claim for the medicinal ingredient, the formulation, the dosage form, or the use of the medicinal ingredient?
Does APO-Dasatinib infringe the ‘898 Patent?
Is the ‘898 Patent invalid because:
the claims are ambiguous;
claims 4, 5, 9, and 10 claim ineligible subject matter;
each of claims 1 to 18 is broader than any invention made or disclosed;
the patent specification is insufficient;
the promised utility of the invention claimed was neither demonstrated nor soundly predicted as of the filing date;
the invention claimed was obvious or obvious to try;
each of the claims is encompassed by the ‘932 Patent (double patenting);
the invention claimed is anticipated by PTC Publication No. WO 2000/052778 (the “‘778 Application”);
the ‘898 Patent does not meet the criteria of a selection patent?
[6] At the hearing the issues were narrowed to the following specific validity issues relating to three claims being asserted by the Applicants as being valid and infringed:
Is claim 27 of the ‘932 Patent invalid because:
the promised utility of the invention was neither demonstrated nor soundly predicted as of the relevant date; or
the disclosure is insufficient?
Is claim 1 or claim 3 of the ‘898 Patent invalid because:
the invention disclosed was obvious or obvious to try; or
the invention disclosed is encompassed by the ‘932 Patent (double patenting)?
B. Burden of Proof
[7] The Applicants bear the legal burden to establish on a balance of probabilities that all the allegations of invalidity asserted are not justified (Abbott Laboratories v Canada (Minister of Health), 2007 FCA 153 at paras 9 to 10; Hoffman-La Roche Ltd v Apotex Inc, 2013 FC 718 at paras 58 to 61).
C. Results
[8] The results of this action are as follows:
The Respondent’s allegation that claim 27 of the ‘932 Patent is invalid is justified because the Applicants did not:
establish that the promised utility of the invention was demonstrated or soundly predicted as of the relevant date.
The allegation of insufficiency is not justified.
The Respondent’s allegation that claims 1 and 3 of the ‘898 Patent are invalid is justified because the Applicants did not:
prove that the invention was not obvious to try; and
show that claims 1 and 3 were not invalid due to double patenting.
II. Background
A. Chronic Myelogenous Leukemia (“CML”)
[9] CML is a cancer affecting the blood, which comprises 15-20% of adult leukemias. In CML, there is an overproduction of myeloid-derived white blood cells and blasts within the bone marrow and blood.
[10] CML is the result of a translocation between chromosomes 9 and 22, creating what is known as the “Philadelphia chromosome”. The translocation results in a fusion gene, BCR-ABL, which is not present in normal cells. The BCR-ABL gene makes the protein tyrosine kinase (“PTK”) Bcr-Abl.
[11] PTKs are a large and diverse group of proteins within cells that phosphorylate tyrosine amino acid residues on other proteins within a cell. PTKs are grouped into “families” depending on the structural similarity between each protein. PTKs within the same family will have similar structures, while PTKs from different families may have very different structures.
[12] Tyrosine phosphorylation is commonly associated with a number of different cellular functions, including cell division and cell survival. Regulated cell division and survival are both important to the homeostasis of the hematopoietic system, and abnormal PTKs, such as Bcr-Abl, which constantly send signals for cells to grow, divide, and survive, can lead to disease.
[13] In CML, Bcr-Abl abnormally signals CML cells to produce too many white blood cells that do not die at a normal rate. Over time, these cells build up in the bone marrow so that there is less room available for healthy blood cells to grow.
[14] CML has three phases: (1) the initial chronic phase; (2) the accelerated phase; and (3) the final phase, in which CML has transformed into acute leukemia.
B. Treatment of CML in the early 2000s
[15] In 2000, the two standard treatments for CML were interferon (IFN-alpha) and hydroxyurea. Both treatments lead to severe side effects, and neither of these treatments were a cure for CML, which could only be accomplished through a stem cell transplant. At this time, it was well known that Bcr-Abl was the main driver of CML.
[16] In 2001, a drug called imatinib (also known as GLEEVEC®, and by the designation STI571) was approved by the United States Food and Drug Administration for the treatment of CML. Imatinib was understood to inhibit Bcr-Abl activity by binding to the kinase domain and inhibiting its ability to phosphorylate tyrosine residues, essentially turning off its unregulated signal. As a result, the CML cancer cells stop proliferating and eventually die. However, similar to interferon and hydroxyurea, imatinib is not curative of CML.
C. Emergence of resistance to imatinib therapy
[17] By 1999-2000, it was known that some patients were developing resistance to imatinib treatment. Often these patients had a mutation in Bcr-Abl at the site to which imatinib binds. The cells containing this mutation would not be affected by imatinib, and would continue to proliferate, eventually out-populating cells that did not contain the mutated Bcr-Abl. Other mechanisms of resistance were also known, such as over-expression of Bcr-Abl, which required a high dosage of imatinib to treat.
[18] The development of imatinib-resistant CML highlighted the need for additional and/or alternative therapeutic approaches to the treatment of CML.
III. The Applicants’ Expert Witnesses
A. Dr. Moshe Talpaz
[19] Dr. Talpaz is the Alexander J. Trotman Professor of Leukemia Research at the University of Michigan. He also serves as the Associate Director of Translational Research at the University of Michigan Cancer Center and Professor of Internal medicine at the Department of Medicine at the University of Michigan.
[20] Dr. Talpaz obtained a MD from the Hadassah Medical School of Hebrew University in Jerusalem, Israel. He completed his residency at Kaplan Hospital, and a fellowship in developmental therapeutics and immunology at the University of Texas MD Anderson Cancer Center. He joined the faculty of the University of Texas MD Anderson Cancer Center in 1981, and subsequently became a tenured, full professor and chair of the Bioimmunotherapy Department. In 2006, he joined the University of Michigan faculty.
[21] Dr. Talpaz has authored or co-authored over 450 journal articles and textbook chapters on CML. He is a member of the American Society of Hematology and is board certified in internal medicine and medical oncology. He is an expert in the area of hematologic malignancies, such as CML.
[22] Between 2003 and 2006, Dr. Talpaz was one of two international principal investigators leading the phase I clinical trial of dasatinib for Bristol-Myers Squibb Company (“BMS”) (Charles Sawyers at the University of California Los Angeles was the second principal investigator). The Respondent points out that Dr. Talpaz failed to disclose (1) the fact that he had received funding from BMS at different times between 2003 and 2016; and (2) the fact that he has sat and currently sits on ad hoc advisory boards for BMS. I do not find this allegation to be of any consequence in this proceeding.
[23] Dr. Talpaz is an expert in CML, and therapeutics development for CML and imatinib-resistant CML.
B. Dr. Mark P. Wentland
[24] Dr. Wentland is a Professor Emeritus in the Department of Chemistry and Chemical Biology at Renssalaer Polytechnic Institute, Troy, NY (“Renssalaer”). Prior to becoming a Professor Emeritus, he was a full professor at Renssalaer.
[25] Dr. Wentland obtained a B.Sc. in chemistry from Central Connecticut State University, in 1966; and a Ph.D. in organic chemistry from Rice University, in 1970. From 1970-1994 he was employed at the Sterling-Winthrop Research Institute (now a part of Sanofi S.A.), as well as at Renssalear. He has authored over 70 peer-reviewed research articles and five reviews/book chapters. He is also an inventor on 32 United States Patents.
[26] Dr. Wentland is an expert in medicinal chemistry, particularly in the area of structure activity relationships and characterization of therapeutic compounds.
C. Dr. Joel Barrish
[27] Dr. Barrish is the Vice-President of Discovery Chemistry at BMS. He is a named inventor on both the ‘932 and ‘898 Patents.
[28] Dr. Barrish obtained a B.A. in chemistry from the University of Pennsylvania, in 1979; and a Ph.D. in organic chemistry from Columbia University in January 1983. Prior to joining BMS in 1988, he worked as a senior scientist at Hoffman-LaRoche. While at BMS he has led teams that have advanced more than 20 compounds into clinical development, including SPRYCEL®.
[29] Dr. Barrish is an expert in drug development at BMS.
D. Dr. Francis Lee
[30] Dr. Lee is the Director of Tumor Pharmacology and Experimental Therapeutics at BMS. He is a named inventor on the ‘898 Patent.
[31] Dr. Lee obtained a B.Sc. in pharmacology from the University of Leeds, in 1980; a M.Sc. in radiation biology from the University of London, in 1981; and a Ph.D. in the Medical Research Council Clinical Oncology and Radiotherapeutics Unit at the University of Cambridge, in 1985. He completed a post-doctoral fellowship at the University of Rochester Cancer Center, in 1987, and became an assistant professor at the University of Rochester. In 1992, Dr. Lee started working at BMS as a Research Investigator.
[32] Dr. Lee is an expert in drug development at BMS.
E. Dr. William L. Jorgensen
[33] Dr. Jorgensen is a Sterling Professor at Yale University, and holds a Whitehead Professorship.
[34] He obtained an A.B. in chemistry from Princeton University, in 1970; and a Ph.D. in chemical physics from Harvard University in 1975. Prior to accepting his position at Yale in 1990, he was a professor in the Department of Chemistry at Purdue University.
[35] Dr. Jorgensen is or has been the editor of several scientific journals. He has published more than 400 peer-reviewed articles. He has also been awarded numerous honours recognizing his contributions to the field of chemistry, particularly computational chemistry.
[36] Dr. Jorgensen is an expert in the development and application of computational tools to facilitate drug discovery.
IV. The Respondent’s Expert Witnesses
A. Dr. B. Douglas Smith
[37] Dr. Smith is a Professor of Oncology at the Johns Hopkins University School of Medicine, and serves on the active staff of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins.
[38] Dr. Smith obtained an A.B. in Biology from Lafayette College, in 1987; and a M.D. from the Medical College of Pennsylvania, in 1992. He completed an internship and a residency in Medicine at the Strong Memorial Hospital, in Rochester, New York, between 1992 and 1994. He was the Chief Resident, Medicine, at the Strong Memorial Hospital in 1994-1995; and he completed an Oncology Fellowship at Johns Hopkins University, in 1998. Since completing his Oncology Fellowship, he has taught and worked at Johns Hopkins University.
[39] Dr. Smith has published over 120 peer-reviewed articles, and has written over 40 book chapters and/or editorials. He has been recognized for his teaching, and is a member of numerous professional societies.
[40] Dr. Smith is an expert in the treatment of patients with hematologic malignancies, and the treatment of patients with acute myeloid leukemia, CML, and myelodysplastic syndrome.
B. Dr. Thomas E. Smithgall
[41] Dr. Smithgall is the William S. McEllroy Professor and Chair of the Department of Microbiology and Molecular Genetics at the University of Pittsburgh School of Medicine.
[42] Dr. Smithgall obtained a B.A. in biochemistry, in 1981; and a Ph.D. in pharmacology from the University of Pennsylvania School of Medicine, in 1986. From 1986-1990, he completed post-doctoral training first in the Department of Pharmacology, University of Pennsylvania School of Medicine and, subsequently, at the Laboratory of Biological Chemistry, National Cancer Institute, National Institutes of Health. Prior to joining the faculty at the University of Pittsburgh School of Medicine, in 1998, he was an assistant professor at Georgetown University School of Medicine, and then the University of Nebraska Medical Center.
[43] Dr. Smithgall has published over 130 peer-reviewed papers, and has written 21 reviews and/or book chapters. He is a named inventor on two United States Patents, one United States Provisional Patent, and one PTC application. He has been recognized for his research, and is a member of numerous professional and scientific societies.
[44] Dr. Smithgall is an expert in PTK structure and function, particularly the Src-family of PTKs.
V. The ‘932 Patent
A. The Patent
[45] The ‘932 Patent is a Patent Cooperation Treaty (“PCT”) application entitled “Cyclic Protein Tyrosine Kinase Inhibitors”, and has an international filing date of April 12, 2000; a publication date of October 26, 2000; and was issued on August 25, 2009. It has a US priority date of April 15, 1999; and its national entry into Canada was October 9, 2001.
[46] The ‘932 Patent relates to cyclic compounds and salts thereof, to methods of using such compounds in treating protein tyrosine kinase-associated disorders such as immunologic and oncologic disorders, and to pharmaceutical compositions containing such compounds.
[47] The Background to the Invention states:
Enhanced activity of PTKs has been implicated in a variety of malignant and non-malignant proliferative diseases. In addition, PTKs play a central role in the regulation of cells of the immune system. PTK inhibitors can thus impact a wide variety of oncologic and immunologic disorders. Such disorders may be ameliorated by selective inhibition of a certain receptor or non-receptor PTK, such as Lck, or due to the homology among PTK classes, by inhibition of more than one PTK by an inhibitor.
[48] The Summary of the Invention states:
The present invention provides cyclic compounds of the following formula I and salts thereof, for use as protein tyrosine kinase inhibitors:
Where Q, Z, X1, X2, R1, R2, R3, R4, and R5 are described in detail on pages 3 to 8 of the patent specification.
[49] The ‘932 Patent describes Schemes A through E, and I through XI, for the preparation of the compounds of formula I, and states that “solvents, temperatures, pressures, and other reaction conditions may readily be selected by one of ordinary skill in the art”.
[50] The ‘932 Patent has a lengthy Utility section, which in part reads:
The compounds of the present invention inhibit protein tyrosine kinases, especially Src-family kinases such as Lck, Fyn, Lyn, Src, Yes, Hck, Fgr, and Blk, and are thus useful in the treatment, including prevention and therapy, of protein tyrosine kinase-associated disorders such as immunologic and oncologic disorders. The compounds inhibit also receptor tyrosine kinases including HER1 and HER2 and are therefore useful in the treatment of proliferative disorders such as psoriasis and cancer. The ability of these compounds to inhibit HER1 and other receptor kinases will also permit their use as anti-angiogenic agents to treat disorders such as cancer and diabetic retinopathy. “Protein tyrosine kinase-associated disorders” are those disorders which result from aberrant tyrosine kinase activity, and/or which are alleviated by the inhibition of one or more of these enzymes.
…
Use of the compounds of the present invention in treating protein tyrosine kinase-associated disorders is exemplified by, but is not limited to, treating a range of disorders such as: [list of at least 30 disorders, including transplant rejection; T-cell mediated hypersensitivity diseases; Addison’s disease; and] cancers, including cancers where Lck or other Src-family kinases such as Src are activated or overexpressed, such as colon carcinoma and thyoma, and cancers where Src-family kinase activity facilitates tumor growth or survival…
The compounds of the formula I may be administered by any suitable means, for example, orally, such as in the form of tablets, capsules, granules or powers; sublingually; buccally; parenterally …
The compounds of the present invention may be employed alone or in combination with each other and/or other suitable therapeutic agents useful in the treatment of protein tyrosine kinase-associated disorders such as PTK inhibitors other than those of the present invention, antiinflammatories (sic), antiproliferatives, chemotherapeutic agents, immunosuppressants, anticancer agents and cytotoxic agents.
…
[51] The ‘932 Patent teaches five assays that were used to test the compounds enumerated in the claims: (1) enzyme assays using Lck, Fyn, Lyn, Hck, Fgr, Src, Blk, or Yes; (2) enzyme assays using HER1 or HER2; (3) cellular tyrosine phosphorylation cell assays; (4) calcium cell assays; and (5) cell proliferation assays. It also contains a list of 580 exemplary compounds that can be created from formula I. However, there is neither a list of specific compounds that were tested using each assay, nor any resultant data.
[52] There are 43 claims in the ‘932 Patent. The parties have agreed that only independent claim 27 is at issue in this action.
[53] Claim 27 states:
The compound
or a salt thereof.
[54] Claim 35 contains the same chemical formula disclosed in claim 27, and states:
Use of a compound or salts thereof for the treatment of cancer…
[55] Claims 36 to 43 depend on claim 35, and claims 37 to 43 disclose the use of the chemical compound in claim 35 for the treatment of gastric cancer, breast cancer, colon carcinoma, colorectal cancer, lung cancer, non-small cell lung cancer, and ovarian cancer.
B. The Relevant Date
[56] The relevant date for assessing whether there was sufficient disclosure and whether utility had been demonstrated is the claim date of the patent, which in this case is the priority date: April 15, 1999.
C. The Persons of Ordinary Skill in the Art (POSITA)
[57] The experts generally agreed on who the POSITA would be for both the ‘932 and ‘898 Patents. They stated the POSITA would not be a single person, but rather a team of skilled people, who together have the skills needed to read and understand the BMS Patents.
[58] Dr. Talpaz stated that the skilled team would be collectively versed in the fields of medicinal chemistry, biochemistry, pharmacology, biology, as well as clinical medicine. He opined that the skilled team would include medical doctors having specialties or training and experience in each of the diseases in the claims.
[59] Dr. Wentland was asked to assume that the POSITA had the following characteristics: a medicinal chemist with an advanced degree in medicinal chemistry or synthetic organic chemistry, with experience in pharmacology and biochemistry; who works with someone having an advanced degree in molecular biology or medicine, with education or experience in the field of cellular signal transduction.
[60] Dr. Smith expressed his opinion that the skilled addressee would be a team of individuals that would include chemists, who would make the compounds and formulations described in the patent; biochemists with experience in testing kinases; pharmacologists, who would be involved in assessing the properties of the compounds; and clinicians who would be involved in studying their use in the of treatment of the indicated conditions. The biochemists and pharmacologists on the team would have backgrounds or experience in oncology, or preferably CML. The clinicians would have received specialized training in oncology, and experience in the treatment of blood cancers, such as CML and other forms of leukemia.
[61] Dr. Smithgall substantially agreed with Dr. Smith’s definition of the POSITA, adding that the non-clinician members of the team would have a high level of training, most likely doctorate degrees and post-doctoral training. They would also have some experience with the diseases contemplated in the BMS Patents.
[62] Having considered the evidence before the Court, I find that the POSITA for the BMS Patents would be a team of skilled persons—who all have graduate level training (e.g. doctoral or post-doctoral training); or medical doctorates, with specialties in oncology or CML—including chemists, biochemists, pharmacologists, and clinicians.
D. Common General Knowledge as of April 15, 1999
(1) Preparation and testing of the compounds in the BMS Patents
[63] The BMS Patents presume that the POSITA would be able to select solvents, temperatures, pressures, and other reaction conditions in order to prepare the compounds of the formula I. Further, all of the experts agreed that the POSITA would know how to conduct screens to analyze the potency of small molecule compounds against PTKs. They also agreed that the POSITA would be able to run these assays in a high density format, which would allow for the testing of many compounds, compound concentrations, or enzyme targets simultaneously.
VI. Validity of the ‘932 Patent
A. Utility
(1) Law
[64] The Patent Act, section 2, defines an “invention” as something that is, amongst other criteria, “new and useful”. Justice Binnie, in Apotex Inc v Wellcome Foundation Ltd, 2002 SCC 77 at paragraph 46, [Wellcome AZT], stated that the inventor must “establish the utility as of the time the patent is applied for, on the basis of either demonstration or sound prediction”. If the patent is subsequently challenged and it is found that “the prediction at the date of application was not sound, or, irrespective of the soundness of the prediction, ‘there is evidence of lack of utility in respect of some of the area covered’” then the patent will be found invalid (Wellcome AZT, above, at para 56).
[65] The doctrine of “sound prediction” is premised upon balancing the public interest in early disclosure of inventions, before their utility has been verified by tests, and the public interest in avoiding granting monopoly rights in exchange for misinformation (Wellcome AZT at para 66). The public is entitled to obtain a solid, meaningful teaching in exchange for the patent rights granted to the inventor (Wellcome AZT at para 69, 83). Therefore, sound prediction is neither speculation nor lucky guesswork, even if it afterwards turns out of be correct (Wellcome AZT at para 84).
[66] The level of disclosure required by the doctrine of sound prediction is to be assessed as a function of the POSITA’s knowledge, and as a function of what the POSITA would understand as a logical line of reasoning (Bell Helicopter Textron Canada Limitée v Eurocopter, société par actions simplifée, 2013 FCA 219 at para 152 [Eurocopter]). Where sound prediction is “reliant on data which does not form part of the common general knowledge, then disclosure in the specification may indeed be required to support a sound prediction” (Eurocopter, above, at para 153).
[67] The predictability of a particular result will depend on the evidence, and the soundness of the prediction is a question of fact (Wellcome AZT at para 71). In Wellcome AZT, at paragraph 70, Justice Binnie laid out three requirements for sound prediction :
1) There must be a factual basis for the prediction.
2) The inventor must have at the date of the patent application an articulable and “sound” line of reasoning from which the desired result can be inferred from the factual basis.
3) There must be proper disclosure. However, it is generally not necessary for an inventor to provide a theory of why the invention works.
[68] A sound prediction requires that there be a factual basis that would lead to a prima facie reasonable inference of utility (Eli Lilly Canada Inc v Novopharm Limited, 2010 FCA 197 at para 85). The inventor has the burden of disclosing both the factual basis and the line of reasoning, which bridges the gap between the factual basis and the predicted utility of the patent, in the patent specification, since it is he or she that will benefit from the monopoly (Apotex Inc v Pfizer Canada Inc, 2011 FCA 236 at paras 44, 52 ).
[69] An inventor does not need to describe the utility of his invention in his patent; however, if he does so, he will be held to the promise which he has made (Sanofi-Aventis v Apotex Inc, 2013 FCA 186 at para 48 [Sanofi Plavix]). If there is no explicit promise of a specific result, the test of utility is a “mere scintilla” of utility; however, if there is an explicit promise, then utility will be assessed by reference to the terms of the explicit promise (Sanofi Plavix, above, at para 49). An inventor can promise more for his or her invention than required by the Patent Act, so as to render the otherwise valid patent invalid (Sanofi Plavix at para 54).
[70] Whether or not the patent contains a specific promise is a matter of construction for the Court (Sanofi Plavix at para 50). To establish the content of the promise, the Court must not use inference, but rather should look for clear unambiguous language in the specification (Sanofi Plavix at para 66; Eli Lilly Canada Inc v Hospira Healthcare Corporation, 2016 FC 47 at para 41). Where the patent can be reasonably read as excluding a promise, the patent will be construed in favour of the patentee (Apotex Inc v Pfizer Canada Inc, 2014 FCA 250 at paras 66 to 67).
[71] Finally, it is settled law that some promises can impose an overarching utility requirement over all of the claims in the patent, while other promises may only affect a certain subset of the claims, and that inutility must then be assessed on a claim-by-claim basis (Astrazeneca Canada Inc v Apotex Inc, 2015 FCA 158 at paras 4 to 5).
(2) Analysis
[72] The Applicants assert that there is no explicit promise contained in the ‘932 Patent and, as such, the standard for determining utility is a “mere scintilla”. They argue that the utility of the ‘932 Patent is only that the compounds disclosed are PTK inhibitors. Further, they submit that there is no unequivocal promise that all of the compounds, including dasatinib, inhibit both Src-family PTKs and receptor PTKs, including HER1 and HER2.
[73] A fair construction of the ‘932 Patent, according to the Applicants, would preclude an overarching promise of therapeutic utility that touches claim 27. They argue that any therapeutic utility only attaches to particular embodiments of the invention, which are associated with the specific claims disclosing use for the treatment of disease (e.g., claims 35-43).
[74] The Applicants also contend that the Respondent cannot rely on the evidence of Dr. Smithgall because his approach to construing the patent to determine whether or not there was a promise was flawed. Particularly, they state that Dr. Smithgall was told to treat all assertions in the patent as promises, and not told to consider the claims in determining what promises were made.
[75] The Applicants state that there was demonstrated utility of claim 27 (i.e., dasatinib) at the filing date of the ‘932 Patent, because dasatinib was shown to inhibit the PTKs Lck and Yes. Further, if there is an explicit promise that dasatinib inhibits both the Src-family PTKs and HER1/HER2, which they deny, they assert that inhibition of HER1 and HER2 was soundly predicted at the filing date based upon the structural similarities of the inhibitors.
[76] Finally, the Applicants argue that the Respondent cannot now resile from the position taken in the ‘932 NOA that the skilled person “would not know whether each of the individual compounds of the invention was being promised as an inhibitor of all PTKs or specific PTKs … all PTK-associated disorders or only certain PTK-associated disorders”. That is, because that the Respondent admits in the ‘932 NOA that the POSITA would not know what the promise entailed, there can be no explicit promise.
(a) The ‘932 NOA
[77] Whether or not there is a promise contained in a patent is a matter of construction for the Court. However, the NOC process is such that the NOA must raise all of the legal and factual arguments, which the party crafting the NOA will rely upon, and subsequently introducing new facts and arguments is improper (Bayer Inc v Cobalt Pharmaceuticals Co, 2013 FC 1061 at para 37, aff’d in 2015 FCA 116; Aventis Pharma Inc v Mayne Pharma (Canada Inc), 2005 FCA 50 at para 25).
[78] The Respondent rejects the assertion that they are estopped by way of the ‘932 NOA from arguing that the ‘932 Patent contains an explicit promise of utility on the basis that the passage relied upon by the Applicants in the ‘932 NOA should be read in the context of an “in the alternative” argument.
[79] The Respondent argues that it is clear in the ‘932 NOA that it has alleged that the inventors made the following unequivocal assertions as to what the compound disclosed in claim 27 of the ‘932 Patent would do:
1) Inhibit PTKs, especially Src-family kinases, and thus be useful in the treatment, including prevention and therapy of PTK-associated disorders such as immunologic and oncologic disorders; and
2) Inhibit also receptor tyrosine kinases, including HER1 and HER2, and thus be useful in treating proliferative disorders, such as psoriasis and cancer.
[80] I agree with the Respondent. The passage relied upon by the Applicants, at page 56 of the ‘932 NOA, indicates that the Respondent is making an alternative argument, which posits that the Court has accepted their overbreadth and ambiguity arguments (no longer live issues at the time of the hearing):
For the reasons described above in respect of Overbreadth and Ambiguity, the skilled person reading the 932 Patent would not know whether each of the individual compounds of the invention was being promised as an inhibitor of all PTKs or specific PTKs. Likewise, the skilled person reading the 932 Patent would not know whether each of the compounds of the invention was being promised as being useful in the treatment of all PTK-associated disorders or only certain PTK-associated disorders. As discussed above, if it was the intention of the inventors that each compound of the invention was only being promised to inhibit a single PTK or a group of PTKs, or to be useful in the treatment of a single PTK-associated disorder or a group of PTK-associated disorders, this information has not been provided in the ‘932 Patent.
(b) Promise of the Patent
[81] The Applicants assert that there is no overarching promise that the compounds inhibit all PTKs and all receptor tyrosine kinases because a POSITA would think that conclusion to be scientifically absurd. Similarly, they contend that there is no promise that the compounds will inhibit both some non-receptor PTKs (e.g., the Src-family) and some receptor tyrosine kinases (e.g., HER1 and HER2). The Applicants also submit that, because the ‘932 Patent has claims that are separated into compound claims, use claims, and pharmaceutical composition claims, there can be no overarching promise of therapeutic utility. Further, they argue that “the potential utility of the compounds as therapeutics is explicitly disclosed in the ‘932 Patent as being ancillary to their utility as PTK inhibitors”.
[82] The Respondent, in the ‘932 NOA, states that the promised utility of the subject matter claimed by the ‘932 Patent would be understood to include therapeutic use (‘932 NOA at 54):
… that the compounds of the invention are PTK inhibitors, and that as a consequence of being PTK inhibitors, the compounds of the invention will be useful in the treatment of PTK-associated disorders such as immunologic and oncologic disorders.
… the ability of the compounds of the invention to inhibit tyrosine kinases including HER1 and HER2 and, as a consequence, to be useful in the treatment of proliferative disorders such as psoriasis and cancer, and, in respect of the compound’s ability to inhibit HER1, to be useful in the treatment of angiogenic disorders such as cancer and diabetic retinopathy.
[83] Contrary to the Applicants’ assertions, there are clear references in the specification that support the view that there is an overarching promise of utility: the Field of the Invention, and the Utility section.
[84] The Field of the Invention states:
The present invention relates to cyclic compounds and salts thereof, to methods of using such compounds in treating protein tyrosine kinase-associated disorders such as immunologic and oncologic disorders, and to pharmaceutical compositions containing such compounds.
[85] The Utility section contains the following statements:
The compounds of the present invention inhibit protein tyrosine kinases, especially Src-family kinases such as Lck, Fyn, Lyn, Src, Yes, Hck, Fgr, and Blk, and are thus useful in the treatment, including prevention and therapy, of protein tyrosine kinase-associated disorders such as immunologic and oncologic disorders.
The compounds inhibit also receptor tyrosine kinases including HER1 and HER2 and are therefore useful in the treatment of proliferative disorders such as psoriasis and cancer. The ability of these compounds to inhibit HER1 and other receptor kinases will also permit their use as anti-angiogenic agents to treat disorders such as cancer and diabetic retinopathy.
…
The present invention thus provides methods for the treatment of protein tyrosine kinase-associated disorders, comprising the step of administering to a subject in need thereof at least one compound of the formula I in an amount effective therefor.
…
Use of the compounds of the present invention in treating protein tyrosine kinase-associated disorders is exemplified by, but is not limited to, treating a range of disorders such as: [list of disorders including cancers where Src-family kinases are activated or overexpressed]
…
In a particular embodiment, the compounds of the present invention are useful for the treatment of the aforementioned exemplary disorders irrespective of their etiology …
[86] Dr. Smithgall testified that a POSITA would understand that the overarching promise of the ‘932 Patent was to (1) inhibit protein tyrosine kinases, especially Src-family kinases; (2) inhibit receptor tyrosine kinases, including HER1 and HER2; and (3) be useful to treat protein tyrosine kinase-associated disorders or useful as anti-angiogenic agents.
[87] On cross-examination, Dr. Smithgall admitted that he was not given any instructions regarding how to read the ‘932 Patent and legally assess utility. The Applicants assert that this makes Dr. Smithgall’s testimony unreliable. The Respondent argues that, while it did not fully instruct Dr. Smithgall on the law of utility, it asked Dr. Smithgall to determine if the ‘932 Patent made “explicit, unequivocal assertions (i.e. promises) as to what the compounds of claims 7 and 27 will do”. Dr. Smithgall’s opinion regarding the promise of the patent remained consistent throughout his cross-examination.
[88] Dr. Jorgensen opined that Dr. Smithgall’s construction of the promise was incorrect, because the POSITA would think that it was scientifically absurd that a compound would inhibit all PTKs and receptor tyrosine kinases. He states that a POSITA would read the ‘932 Patent and conclude that the only expectation was that a compound would inhibit at least one PTK or receptor tyrosine kinase. Dr. Smithgall agreed that a POSITA would not expect each compound to inhibit all of the PTKs. However, he contended that the promise, as he understood