Novartis Pharmaceuticals Canada Inc v. Cobalt Pharmaceuticals Company

Novartis Pharmaceuticals Canada Inc v. Cobalt Pharmaceuticals Company
Court (s) Database
Federal Court Decisions
Date
2013-09-25
Neutral citation
2013 FC 985
File numbers
T-724-12
Decision Content
Date: 20130925
Docket: T-724-12
Citation: 2013 FC 985
Toronto, Ontario, September 25, 2013
PRESENT: The Honourable Mr. Justice Hughes
BETWEEN:
NOVARTIS PHARMACEUTICALS
CANADA INC.
Applicant
and
COBALT PHARMACEUTICALS COMPANY
and THE MINISTER OF HEALTH
Respondents
and
NOVARTIS AG and
ROCHE DIAGNOSTICS GmbH
Respondent Patentees
REASONS FOR JUDGMENT AND JUDGMENT
[1] This is an Application brought under the provisions of the Patented Medicines (Notice of Compliance) SOR/93-133 (NOC Regulations) wherein the Applicant Novartis is seeking to prohibit the Minister of Health from issuing a Notice of Compliance to the Respondent Cobalt in respect of a drug containing zoledronic acid to be administered in once-yearly doses for the treatment of osteoporosis in humans until the expiry of Canadian Letters Patent Number 2,410,201 on June 18, 2021.
[2] For the reasons that follow, I find that the application is dismissed.
[3] The following is an index to these Reasons by paragraph number:
THE PARTIES
Paras 4 - 8
THE '201 PATENT GENERALLY
Paras 9 - 14
THE EVIDENCE
Paras 15 - 18
ISSUES
Paras 19 - 22
BURDEN
Para 23
BONES - BISPHOSPHONATES
Paras 24 - 30
THE '201 PATENT - IN DETAIL
Paras 31 - 45
THE CLAIMS OF THE '201 PATENT
Paras 46 - 49
PERSON SKILLED IN THE ART
Paras 50 - 55
CONSTRUCTION OF THE CLAIMS
Paras 56 - 59
ISSUE #1: OBVIOUSNESS
Paras 60 - 69
ISSUE #2: METHOD OF MEDICAL TREATMENT
Paras 70 - 101
ISSUE #3: NOC LISTING
Paras 102 - 110
CONCLUSIONS AND COSTS
Paras 111-112
THE PARTIES
[4] The Applicant Novartis Pharmaceuticals Canada Inc. (Novartis) is described as a “first person” in the NOC Regulations. It has received approval from the Minister of Health, by way of a Notice of Compliance, to market in Canada a drug containing zoledronic acid (also called zoledronate) for once-a-year administration in the treatment of osteoporosis in humans. It markets that drug under the brand name ACLASTA. Novartis has listed Canadian Letters Patent Number 2,401,201 under the provisions of the NOC Regulations.
[5] The Respondent Cobalt Pharmaceuticals Company (Cobalt) is described as a “second person” in the NOC Regulations. It seeks approval by way of a Notice of Compliance from the Minister of Health to market a generic version of Novartis ACLASTA drug in Canada.
[6] The Respondent Minister of Health (Minister) has been served with the relevant documents in these proceedings, but has taken no active part. The Minister is charged under the NOC Regulations with various duties, including the issuance, or not, of a Notice of Compliance in appropriate circumstances.
[7] The Respondent Novartis AG is recorded as the owner of the patent at issue but has taken no active part in these present proceedings.
[8] The Respondent Roche Diagnostics GmbH has taken no active part in these present proceedings.
THE '201 PATENT GENERALLY
[9] Canadian Letters Patent Number 2,410,201 (the '201 patent) were issued and granted to the Respondent Novartis AG on October 26, 2010. The application for that patent was filed with the Canadian Patent Office under the provisions of the Patent Cooperation Treaty (PCT) effective as of June 18, 2001. Since that application was filed subsequent to October 1, 1989, the provisions of the “new” Patent Act, RSC 1985, c. P-4 are applicable to this patent.
[10] The application claimed priority from applications filed in the United States Patent Office on June 20, 2000, and another on February 9, 2001.
[11] The application for the patent became available to the public (publication date) on December 27, 2001.
[12] The ‘201 patent names Peter C. Richardson, Zebulun D. Horowitz and Ulrich Trechsel as inventors. One of them, Richardson, gave evidence in these proceedings.
[13] The '201 patent, unless earlier declared invalid in proceedings other than this one, will expire twenty (20) years from its Canadian filing date; that is, on june 18, 2021.
[14] The patent contains 41 claims. At the hearing Novartis’ Counsel withdrew reliance upon any of claims 37 to 41 (the so-called “kit” claims) therefore they are no longer at issue here.
THE EVIDENCE
[15] As is usual in proceedings of this kind, the evidence took the form of affidavits and transcripts of the cross-examination upon those affidavits; together with exhibits as identified.
[16] The Applicant Novartis filed the affidavits of the following witnesses:
1. Peter Richardson of Fort Worth, Texas: He was a fact witness and, as one of the named inventors of the '201 patent, gave evidence as to the research and development leading to and surrounding that patent. He was cross-examined.
2. Dr. Nora Zorich of Cincinnati, Ohio: She was offered as an expert witness; no challenge was made by Cobalt in that respect. She spent many years with Proctor & Gamble in the development of bisphosponate drugs for the treatment of bone disease. Since her retirement in June 2012, she has been working as an independent consultant in respect of pharmaceuticals, over-the-counter drugs and dietary supplements. She addressed issues of obviousness and method of medical treatment respecting the '201 patent. She was cross-examined.
3. Dr. Frank H. (Hal) Ebetino of Venice, Florida: He was offered as an expert witness; no challenge was made by Cobalt in that respect. He claims expertise and extensive experience in the discovery and development of bisphosphonates. He began working with bisphosphonates at Proctor & Gamble in the 1980’s. In 2010, he moved to Ireland to lead the Drug Discovery Department at Warner-Chilcott. Since 2012, he has his own consulting firm practising in the pharmaceutical field. He was cross-examined.
4. Erin McIntomny of Ottawa, Ontario: She is a law clerk employed by the law firm acting for Novartis in these proceedings. Her affidavit served to make of record certain correspondence between the solicitors for the parties herein. She was not cross-examined.
[17] The Respondent Cobalt filed the affidavits of the following witnesses:
1. Dr. Terrance L. Baker of Kingsville, Maryland: He was offered as an expert witness; no challenge was made by Novartis in that respect. He is a practicing medical doctor specializing in many areas, including osteoporosis, an area in which he has extensive experience. He addressed the '201 patent, including whether the claims encroach on his skill and judgment as a physician. He was cross-examined.
2. Dr. William Singer of Port Credit, Ontario: He is an Honorary Consultant Physician in the Division of Endocrinology and Medicine at St. Michael’s Hospital, and Staff Physician at the LMC Endocrinology Centre in Toronto; as well as an Associate Professor of Medicine at the University of Toronto. He was offered as an expert witness; no challenge was made by Novartis in that respect. He provided opinions respecting the '201 patent, including obviousness. He was cross-examined.
[18] There is no confidentiality Order.
ISSUES
[19] This proceeding began by putting three patents in issue. By the Order of Prothonotary Tabib dated May 30, 2012, the present proceeding dealing only with the '201 patent has been heard separately from proceedings respecting the other two patents.
[20] Only the validity of the '201 patent is at issue. Infringement is not an issue. As to validity, there are two issues to be determined:
1. Obviousness; and
2. Is the subject matter ineligible for patent protection – is it a method of medical treatment?
[21] A third issue arose during the exchange of the parties’ memoranda of argument; namely:
3. Is the '201 patent one that can properly be listed under the NOC Regulations?
[22] Novartis argues that it is too late for Cobalt to raise this argument.
BURDEN
[23] Who bears the burden when validity of a patent is at issue in NOC proceedings has been discussed many times in this Court. In brief: a patent is presumed to be valid in the absence of evidence to the contrary (Patent Act, s. 43(2)). The party alleging invalidity (here Cobalt) has the burden of putting forth evidence supporting its allegations. Once evidence is led the matter is determined by the Court on the civil burden of proof; namely, balance of probabilities. If the Court finds the matter to be evenly balanced, then it should find in favour of the person alleging invalidity since, under the NOC Regulations, subsection 6(2), the first person (here Novartis) bears the burden of demonstrating that the allegations of invalidity are not justified.
BONES - BISPHOSPHONATES
[24] Bones are a major organ in the human body. They are made up of collagen, minerals and cells. Bones are continuously reformed. Bone tissue is degraded and resorbed into the body through the activity of osteoclasts. New material from the body, through the activity of oseoblasts, is layered on the bone and becomes mineralized so as to replace the lost bone tissue. The whole process is described as remodelling. An entire cycle for remodelling a bone is in the order of a hundred days.
[25] When the remodelling proceeds in a normal way, all is well. When more bone material is deposited than is resorbed, unwanted growth develops; an extreme form of which is called Paget’s disease. When more material is resorbed than is deposited, conditions such as osteoporosis occur. An extreme form brought about by certain cancers is hypercalcemia of malignancy.
[26] It has long been known that at least some members of a class of chemical compounds known as bisphosphonates are useful in regulating bone remodelling. Early versions included etidronate and clodronate. Etidronate was the subject of early NOC litigation in this Court; for example, Proctor & Gamble Pharmaceuticals Canada Inc v Canada (Minister of Health), 2004 FC 204.
[27] Over the course of time, other bisphosphonates have been developed. One of the most recent is zoledronate, which was the subject of my recent decision, now under appeal, Novartis Pharmaceuticals Canada Inc v Teva Canada Limited, 2013 FC 283.
[28] At the hearing, Novartis’ Counsel accepted the following assertions made at paragraph 70 of Cobalt’s Memorandum:
70. As of June 20, 2000, the claim date of the '201 patent, it was known that:
i. Bisphosphonates such as zoledronic acid, etidronate, clodronate, pamidronate, alendronate, risedronate and ibandronate were useful in the treatment of bone diseases;
ii. Zoledronic acid, etidronate, alendronate and risedronate were useful in the treatment of osteoporosis;
iii. Zoledronic acid was one of the most potent anti-resorptive bisphosphonates .
[29] I accept that the evidence demonstrates, as asserted by Novartis at paragraph 24 of its Memorandum, that by June 2000, a handful of bisphosphonates had received government approval to be sold for the treatment of different metabolic bone diseases; including Paget’s disease, hypercalcemia of malignancy and osteoporosis. However, zoledronate had not yet been approved for any indication. Further, no clinical test results for zoledronate in the treatment of osteoporosis had been published as of that time.
[30] I also accept that as of June 2000, the prevailing method of treatment of osteoporosis by the use of a bisphosphonate was to administer low doses orally; usually one a day for a period of days, followed by a rest period; repeated, as needed. I also accept that as of June 2000, certain bisphosphonates were administered weekly instead of daily. I further accept that the literature postulated that less frequent dosing may be desirable provided that it was effective.
THE '201 PATENT – IN DETAIL
[31] It is tempting in patent proceedings for the Court to be distracted from what the patent says by the evidence of experts and others, as well as the argument of Counsel. It must be remembered that the proceedings are about the patent, which is a document that must, as provided for in section 27(3)(a) of the Patent Act, correctly and fully describe the invention and its operation as contemplated by the inventor and, as provided in section 27(a) of that Act, end with claims that define distinctly and in explicit terms the subject matter of the invention. The patent is something drafted by persons seeking a patent monopoly; thus, if they say something in a patent, they must accept what is said is their position in the matter, notwithstanding what experts or others may say later. I addressed this in part in Merck & co. Inc v Pharmascience Inc, 2010 FC 510 at paragraph 8:
8 The '457 Patent is to be read from the viewpoint of a person skilled in the art to which it pertains as of the publication date, April 20, 1995. It must be remembered that statements made by the patentee, such as what constitutes the prior art, are to be treated as binding admissions by the patentee (Eli Lilly Canada Inc. v. Novopharm Limited, 2007 FC 596, 58 C.P.R. (4th) 214 at para. 142 (FC); Whirlpool Corp. v. Camco Inc. (1997), 76 C.P.R. (3d) 150 at page 186 (F.C.T.D.), affirmed [2000] 2 S.C.R. 1067; Shire Biochem Inc. v. Canada (Minister of Health), 2008 FC 538, 67 C.P.R. (4th) 94 at para. 24;Pfizer Canada Inc. v. Novopharm Limited, 2005 FC 1299, 42 C.P.R. (4th) 502 at para. 78).
[32] In the present proceedings, Cobalt does not challenge the '201 patent for insufficiency or lack of utility. The only validity issues are obviousness and method of medical treatment. Thus, the Court must assume that the description provided in the patent is sufficient for a person skilled in the art to put the invention into practice, and that the invention is useful.
[33] The '201 patent begins at page 1 by stating that the invention relates to the pharmaceutical use of bisphosphonates in the treatment of conditions such as osteoporosis. It acknowledges that bisphosphonates have been widely known, used and proposed for use in treating osteoporosis. It says, in part:
This invention relates to bisphosphonates, in particular to the pharmaceutical use of bisphosphonates in the treatment of conditions of abnormally increased bone turnover, such as osteoporosis.
Bisphosphonates are widely used to inhibit osteoclast activity in a variety of both benign and malignant diseases in which bone resorption is increased.
. . .
In addition bisphosphonates have been proposed for use in the treatment of osteoporosis. Thus for instance…
. . .
[34] Beginning at the bottom of page 2, through pages 2a, 2b, 2c, and to the first part of page 3, the patent describes what the invention is. That description takes several forms, such as “use of zoledronic acid” or “use of zoledronic acid…in the manufacture of a medicament” or “zoledronic acid…for treatment of a condition” or “a pharmaceutical composition comprising…zoledronic acid”. These are different ways of describing the invention and reflect practices, particularly in Europe, where for a long time claims directed to a medicine or use of a medicine were prohibited or restricted. Ways were devised to get around such restrictions, including a so-called “Swiss claim”, i.e. “the use of A in the manufacture of a medicament to treat condition B”, which was discussed at length in my decision Merck & Co Inc v Pharmascience Inc, 2010 FC 510, supra. I will repeat only a portion of what is written at pages 2 and following, of the '201 patent:
[35] It is to be noted that the above description is directed only to one bisphosphonate; namely, zoledronate. However, beginning at the bottom of page 3, the patent discusses treatment at intervals of six months or a year, or in between; or greater, in the context of a broad range of bisphosphonates, including the previously known ones such as clodronate, pamidronate, alendronate, risedronate, and others; as well as zoledronate. It says at pages 3 to 5:
[36] Beginning about one-third down page 5 and over to page 6, of the '201 patent, a number of preferred bisphosphonates are identified, including: pamidronate, alendronate, ibandronate, risedronate, zoledronate, and others. In other words, several previously known bisphosphonates, as well as zoledronate, are said to be preferred for the once every six months or once a year administration.
[37] At page 9, it is stated that zoledronic acid is the most preferred:
[38] The patent then describes from pages 9 to 11 that a number of different salts can be used, isomers of the bisphosphonates can be used, the material can be formulated into pharmaceutical compositions, and that a number of different modes of administration – oral, rectal, intravenous and so forth – may be used. Intravenous is the most preferred.
[39] At page 11, there is a discussion of dosage which “depends on various factors”. Most preferred is a single dose in a range of 0.005 – 20 mg/kg; especially 0.01 – 10 mg/kg. This dosage is administered intermittently every six months or once a year or longer. A particular dosage depends on factors such as age, weight, lifestyle, and so forth.
[40] At page 12, the patent asks the reader to appreciate that the unit dose to be used will depend on the potency of the bisphosphonate, dosing interval, and mode of administration. Zoledronic acid is described as a more potent bisphosphonates.
…It will be appreciated that the actual unit dose used will depend upon the potency of the bisphosphonates, the dosing interval and route of administration amongst other things. Thus the size of the unit dose is typically lower for more potent bisphosphonates and greater the longer the dosing interval. For example, the more potent, N-bisphosphonates such as zoledronic acid a unit dose of from about 1 up to about 10 mg may be used for a parenteral, e.g. intravenous, administration. For example, also for more potent N-bisphosphonates a unit dose of from about 1 to about 5 mg may be used parenterally for dosing once every 6 months; whereas a dose of from about 2 up to about 10 mg may be used for once a year parenteral dosing.
[41] The patent proceeds to describe the form that the dosages may take and other matters.
[42] A number of Examples, one to five, are provided. They are preceded by the statement at page 14 that any of the previously mentioned bisphosphonates could be the active ingredient in the Examples.
[43] Example 5, beginning at page 18 of the patent, is specific to zoledronate. It describes a test conducted on three hundred and fifty-one patients suffering from post-menopausal osteoporosis. They are randomly divided into six groups (study arms), one group is given a placebo and the others different dosages of zoledronic acid over different intervals. The results are presented in a table found at page 19:
[44] The conclusion stated at page 20 is that dosages of zoledronate as infrequent as every six to twelve months can safely and significantly result in increased bone mass and reduce risk of osteoporotic fracture:
[45] The claims follow.
THE CLAIMS OF THE '201 PATENT
[46] The claims at issue - claims 1 to 36 - can be considered as being in different groups; each with a general claim, followed by more specific claims. The specific claims in each group are essentially the same. The general claims differ only in the manner in which they are expressed. I accept Novartis’ Counsel’s summary as to these groups of claims as set out in paragraph 61 of Novartis’ Memorandum, noting that claims 37 and following are no longer at issue, and that ZA is an acronym for zoledronate or zoledronic acid:
61. There are 5 types of claims in the Patent:
a. Claims 1-9 are Swiss-type claims, in that they relate to the use of ZA in the manufacture of a medicament;
b. Claims 10-18 are use claims, in that they relate to the use of ZA;
c. Claims 19-27 are claims to a compound (i.e. ZA);
d. Claims 28-36 are claims to a pharmaceutical composition containing ZA; and
e. Claims 37-39 are claims to a kit containing ZA.
[47] I will set out in full claims 10 to 18:
[48] Claim 16 is representative of the claims most focused upon in argument. It is written in dependent form referring back to any of claims 10 to 14. To incorporate the limitations of those earlier claims, claim 16 can be written as follows:
“Use of zoledronic acid, a pharmaceutically acceptable salt thereof, or a hydrate thereof for the treatment of postmenopausal osteoporosis wherein the zoledronic acid, salt or hydrate is in a unit dosage form of about 5 mg which is administered intermittently, with a period of about one year between the first and each subsequent administration, wherein each administration is intravenous.”
[49] This definition coincides with Novartis’ commercial product, which is sold in a vial containing 5 mg of zoledronate for intravenous administration once a year.
PERSON SKILLED IN THE ART
[50] Novartis and Cobalt disagree as to a definition of the notional “person of ordinary skill in the art” (POSITA), to whom the patent is addressed and through whose eyes the patent is to be read.
[51] Novartis submits that it is a person “knowledgeable with respect to the treatment of PMO (postmenopausal osteoporosis) with BP’s (bisphosphonates), including those with experience in chemistry, biopharmaceuticals and experience in designing and interpreting chemical trials.” Novartis’ expert witnesses fit this profile.
[52] Cobalt submits that it is “a medial doctor who has experience treating patients with abnormal bone mechanism disorders or bone disorders such as osteoporosis and Paget’s disease. Such a medical doctor would be a specialist in endocrinology, geriatrics, rheumatology, and/or oncology.” Cobalt’s expert witnesses fit this profile.
[53] In reading the '201 patent, I am inclined to accept the Cobalt definition. At page 1, the patent begins:
This invention relates to bisphosphonates, in particular the pharmaceutical use of bisphosphonates in the treatment of abnormally increased bone turnover such as osteoporosis.
(emphasis added)
[54] At page 2a, the patent says:
Accordingly, the present invention provides a method of treatment of conditions which comprise intermittently administering an effective amount of a bisphosphonate to a patient…
(emphasis added)
[55] Fortunately, at the hearing Counsel for each of the parties agreed that it does not really matter which of the definitions the Court accepts; both should be equally applicable.
CONSTRUCTION OF THE CLAIMS
[56] Each of the parties focused in their Memoranda on the construction of claim 7, which ultimately depends on claim 1, which is written in “Swiss” form. I have focused more on claim 16, which avoids the Swiss form and is written directly as a use claim. Regardless, the construction of claim 7 made by each party in their Memoranda is remarkably similar.
[57] Novartis, at paragraphs 64 – 67 of its Memorandum, construes claim 7 and other claims as follows:
64. Claim 7/5/4/3/2/1: Claim 7, as dependent on claims 5, 4, 3, 2 and 1 would be read by the PSIA as related to the use of ZA in the manufacture of a medicament:
• For the treatment of PMO;
• Wherein the ZA (or salt or hydrate) will be used for intermittent administration;
• The period between the first administration and each subsequent administration is about 1 year; and
• The vial contains about 5 mg of the zoledronic acid, the salt or the hydrate.
65. Claim 7/3/2/1: This claim would be read in a similar fashion, except that it does not specify the amount of ZA in the vial.
66. Summarized in the following table is the construction of the remainder of the claims that Novartis focuses on specifically for the purpose of this proceeding:
Claim 16/14/13/12/11/
10 covers the use of ZA:
Claim 25/23/22/
21/20/19 covers the compound ZA:
Claim 34/32/31/30/29/28 covers a pharmaceutical composition containing ZA:
• For the treatment of PMO;
• Wherein the ZA (or salt or hydrate) will be used for intermittent administration;
• The period between the first administration and each subsequent administration is 1 year +/- 1 month; and
• The vial contains about 5 mg of the ZA, the salt or hydrate.
67. As with Claim 7/3/2/1, Claims 16/12/11/10, 25/21/20/19 and 34/30/29/28 would be read similarly, except that they do not specify the amount of ZA in the vial.
[58] Cobalt at paragraph 50 of its Memorandum submits:
Cobalt submits that the proper construction is a purposive, not literal interpretation. Therefore, claim 7 claims the:
▪ use of zoledronic acid
▪ for the treatment of PMO
▪ by administering the zoledronic acid intermittently with a period of at least about one year between each administration
▪ wherein the administration is intravenous administration
▪ wherein the amount of zoledronic acid is unspecified (claim 7 dependent on claims 3, 2, 1) or wherein the amount is 5 mg (claim 7 dependent on claims 5, 4, 3, 2, 1)
[59] I accept each of these submissions, as they are essentially the same.
ISSUE #1: OBVIOUSNESS
[60] One of the most difficult issues faced by a Court in patent litigation is that of obviousness. The Court must address the alleged invention through the eyes of a person skilled in the art and ask whether it is deserving of patent protection; that is, whether it is either inventive or obvious.
[61] The rationale has been put well by Professor Carl Moy of William Mitchell College of Law, author of Moy’s Walker on Patents, Thomson/West, in addressing a Master of Law Class at Osgood Hall Law School. He said that a patent is a bargain between the public and the patentee which provides a monopoly to a person (patentee) in respect of certain scientific subject matter, provided that it is purchased from the public by disclosing something that is new, useful and inventive. If it is not new, then the monopoly has been purchased for nothing and cannot be valid. If it is something that that the public would get anyway from a person of ordinary skill practicing their craft, then nothing has been paid for the monopoly and the monopoly cannot be valid.
[62] The concepts of inventiveness or obviousness are elusive, which has caused the Courts to endeavour to articulate tests and criteria to be examined and assessed against the evidence. The current state of such tests in Canada is that set out by the Supreme Court of Canada in Apotex Inc v Sanofi-Synthelabo Canada Inc, 2008 SCC 61, [2008] 3 SCR 265 (“Plavix”), per Rothstein J, for the Court, at paragraphs 67 and 69 to 70:
67 It will be useful in an obviousness inquiry to follow the four-step approach first outlined by Oliver L.J. in Windsurfing International Inc. v. Tabur Marine (Great Britain) Ltd., [1985] R.P.C. 59 (C.A.). This approach should bring better structure to the obviousness inquiry and more objectivity and clarity to the analysis. The Windsurfing approach was recently updated by Jacob L.J. in Pozzoli SPA v. BDMO SA, [2007] F.S.R. 37, [2007] EWCA Civ 588, at para. 23:
In the result I would restate the Windsurfing questions thus:
(1) (a) Identify the notional "person skilled in the art";
(b) Identify the relevant common general knowledge of that person;
(2) Identify the inventive concept of the claim in question or if that cannot readily be done, construe it;
(3) Identify what, if any, differences exist between the matter cited as forming part of the "state of the art" and the inventive concept of the claim or the claim as construed;
(4) Viewed without any knowledge of the alleged invention as claimed, do those differences constitute steps which would have been obvious to the person skilled in the art or do they require any degree of invention? [Emphasis added.]
It will be at the fourth step of the Windsurfing/Pozzoli approach to obviousness that the issue of "obvious to try" will arise.
. . .
69 If an "obvious to try" test is warranted, the following factors should be taken into consideration at the fourth step of the obviousness inquiry. As with anticipation, this list is not exhaustive. The factors will apply in accordance with the evidence in each case.
(1) Is it more or less self-evident that what is being tried ought to work? Are there a finite number of identified predictable solutions known to persons skilled in the art?
(2) What is the extent, nature and amount of effort required to achieve the invention? Are routine trials carried out or is the experimentation prolonged and arduous, such that the trials would not be considered routine?
(3) Is there a motive provided in the prior art to find the solution the patent addresses?
70 Another important factor may arise from considering the actual course of conduct which culminated in the making of the invention. It is true that obviousness is largely concerned with how a skilled worker would have acted in the light of the prior art. But this is no reason to exclude evidence of the history of the invention, particularly where the knowledge of those involved in finding the invention is no lower than what would be expected of the skilled person.
[63] The Federal Court of Appeal subsequently dealt with this test and, in particular, the question of motivation in Apotex Inc v Pfizer Canada Inc, (2009), 72 CPR (4th) 141, 2009 FCA 8. That Court distinguished as between “obvious to try” and “more or less self-evident”. The Court rejected the “obvious to try” test if it was based on the “possibility” that something might work, and accepted the “more or less self-evident” test. Noel JA wrote at paragraphs 43 to 45:
43 The reasoning advanced by Mr. Justice Laddie and approved by the English Court of Appeal is that where the motivation to achieve a result is very high, the degree of expected success becomes a minor matter. In such circumstances, the skilled person may feel compelled to pursue experimentation even though the chances of success are not particularly high.
44 This is no doubt the case. However, the degree of motivation cannot transform a possible solution into an obvious one. Motivation is relevant in determining whether the skilled person has good reason to pursue "predictable" solutions or solutions that provide "a fair expectation of success" (see respectively the passages in KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727 (2007) at page 1742 and Angiotech Pharmaceuticals Inc. v. Conor Medsystems Inc., [2008] UKHL 49, at paragraph 42, both of which are referred to with approval in Sanofi-Synthelabo, supra, at paragraphs 57 and 59).
45 In contrast, the test applied by Mr. Justice Laddie appears to be met if the prior art indicates that something may work, and the motivation is such as to make this avenue "worthwhile" to pursue (Pfizer Ltd., supra, para. 107, as quoted at para. 42 above). As such, a solution may be "worthwhile" to pursue even though it is not "obvious to try" or in the words of Rothstein J. even though it is not "more or less self-evident" (Sanofi-Synthelabo, supra, para. 66). In my view, this approach which is based on the possibility that something might work, was expressly rejected by the Supreme Court in Sanofi-Synthelabo, at paragraph 66.
[64] These principles have been applied recently by the Federal Court of Appeal in Sanofi-Aventis v Apotex Inc, 2013 FCA 186, wherein the Court of Appeal found that the Trial Judge had erred in concluding that if the necessary techniques were available to arrive at the alleged invention, the invention itself was obvious. Pelletier JA (with whom Noel JA agreed) wrote at paragraphs 73 and 74:
73 With these facts in mind, the Supreme Court articulated why the separation of the racemate was not obvious to try. It held that just because the methods of separating a racemate into its isomers are known, it does not follow that a person skilled in the art would necessarily apply them. The Supreme Court explained:
It is true that at the relevant time there was evidence that a skilled person would know that the properties of a racemate and its isomers might be different. However, a possibility of finding the invention is not enough. The invention must be self-evident from the prior art and common general knowledge in order to satisfy the "obvious to try" test. That is not the evidence in this case.
Plavix, cited above, at paragraph 85
However, the prior patent did not differentiate between the efficacy and the toxicity of any of the compounds it covered. This suggests that what to select or omit was not then self-evident to the person skilled in the art.
Plavix, cited above, at paragraph 90
74 What emerges from this review of the Supreme Court's decision in Plavix, cited above, is that the key factor in its "obvious to try" analysis was the lack of knowledge of the properties of the enantiomers of the compounds of the '875 Patent, including the racemate from which clopidogrel was obtained. Absent that knowledge, it was not obvious to try to resolve the racemate, or any other compound, so as to obtain the enantiomer having those advantageous properties.
and at paragraph 81:
81 Given that the Trial Judge applied the test for obviousness set out in Plavix, and given that he applied it to the same material facts as the Supreme Court, he ought to have come to the same conclusion. His error lay in failing to recognize that the unknown nature of the properties of the enantiomers of PCR 4099, or of any of the other compounds of the '875 Patent, was fatal to the "obvious to try" analysis. Put another way, the distance between the common general knowledge and the inventive concept of the '777 Patent could not be bridged by routine experimentation since the results to be obtained were unknown. On the facts, this was confirmed by the fact that the inventors, who had more knowledge that the person of ordinary skill in the art, attempted to resolve a number of other compounds before finally trying PCR 4099: see Reasons, at paragraphs 752-759.
[65] Gauthier JA wrote concurring reasons. At paragraph 137 she wrote:
137 The Trial Judge believed that the evidence before him with respect to the separation of the enantiomers was significantly different from the evidence before the Supreme Court of Canada in Plavix because: i) he found that a line had been drawn in the sand at the time the application was filed, and that as part of the process of developing a racemic drug a sponsor would be motivated to separate the enantiomers to get information to pre-empt expected new regulatory requirements (See Reasons at paragraphs 748-749); and ii) in his view, the separation itself did not involve substantial difficulties and was routine. However, Rothstein J. made it clear in Plavix that whether the separation or resolution of the enantiomers was routine or involved arduous work would assume small significance in this case when one considers the whole course of conduct that led to the decision to separate (See Plavix at paragraph 89).
[66] I will turn to the various criteria for assessing obviousness as set out by the Supreme Court in Sanofi, supra, as further considered by the Federal Court of Appeal in Apotex and Sanofi Aventis, supra.
• Person Skilled in the Art
This has been discussed previously in these Reasons.
• Relevant common general knowledge
I have discussed this to some extent under the caption BONES – BISPHOSPHONATES. In considering the subject of the common general knowledge as of mid-2000, I rely more heavily on the expert evidence of Dr. Zorich and Dr. Ebetino. They were working in the field at the time and have provided clear and cogent evidence on the point. I am placing less weight on the evidence of Dr. Singer. He appears familiar with the area, but was clearly less involved than either Dr. Zorich or Dr. Ebetino at the relevant time. Further, Dr. Singer’s evidence is flawed in that he did not conduct a search for the prior art that he relies upon in his evidence. A bundle of prior art was given to him by Cobalt’s Counsel. How and where they found it, we don’t know.
In dealing with common general knowledge, the Court must consider the knowledge that a person skilled in the art at the relevant date would have or would have obtained through a reasonably diligent search conducted by that person using the means available at the relevant time. A search later conducted with the benefit of hindsight is not the best way to put the Court in a position to assess the common general knowledge at the time.
I am, however, sceptical of the evidence of Drs. Zorich and Ebetino on the point that each bisphosphonate must be considered on its own, and that experience with one cannot be translated into experience with another. In brief, they say that the consideration is an empirical one. I am not sceptical on the basis that such evidence has been shown to be wrong. It has not. Rather, I am sceptical because the description in the '201 patent lumps all bisphosphonates; zoledronate, as well as the earlier ones such as elindronate and alendronate, together. The patent suggests that all could usefully be administered in a cyclic pattern of months between administration. Perhaps this is not true, but no challenge has been made to the '201 patent in that regard. The point is that neither Dr. Zorich nor Dr. Ebetino chose to give evidence as to why their evidence is to be preferred to what the '201 patent apparently teaches.
Dr. Ebetino, in particular, provides evidence as to the mechanism by which bisphosphonates are believed to work in affecting bone remodelling. The '201 patent says nothing about the mechanism, nor does it attempt to tie in some form of mechanism to the dosage or intervals of treatment save only to say at page 12, lines 2 and 3, that the dose will depend upon the potency of the bisphosphonates.
Dr. Ebetino frankly admits at paragraph 86 of his affidavit that it was not until well after June 2000 that people working in the field realized the inaccuracy of the assumption that all bisphosphonates with the same R1 group had similar binding affinities at clinically relevant concentrations, and that these differences may be chemically important.
At paragraphs 39 and 40 of his affidavit, Dr. Ebetino frankly admits that, even today, we do not know why zoledronate displays such a long duration of action.
I accept Dr. Zorich’s evidence at paragraphs 146 to 148 of her affidavit that, as of mid 2000, it would not have been evident to a person skilled in the art that once-a-year dosing of zoledronate would be statistically better than a placebo. I accept what she says that while some pharmaceutical companies may have privately been conducting tests as to less frequent dosing, the predominant view was that dosing such as daily or weekly was required, and that dosing intervals greater than three months would have been “off the radar”. I accept her conclusion at paragraph 165 that a person skilled in the art would not have expected that the time period between dosing could be extended to one year without losing efficacy of the bisphosphonate.
• The inventive concept
Novartis, in its written argument, paragraph 103, submits that the inventive concept of the claims is that zoledronate is effective to treat postmenopausal osteoporosis by continuously inhibiting bone resorption when administered only once per year. I disagree that the inventive concept had a grasp that the mechanism was “by continuously inhibiting bone resorption”. No mechanism is stated in the '201 patent.
Cobalt submits at paragraph 98 of its memorandum that the inventive concept of claim 7 lies in the dosage regimen; namely, the approximately once-a-year intermittent dosing of zoledronate to treat postmenopausal osteoporosis. This definition, which I accept, ties in closely with what Richardson, one of the named inventors of the'201 patent, gave in answer to question 36 of his cross-examination:
36 Q. And I would take it that it wasn’t a surprise that zoledronic acid could treat postmenopausal osteoporosis. The dosing regimen, frequency, route of administration were things to be determined, but the fact that zoledronic acid could treat postmenopausal osteoporosis was not unexpected.
A. That’s true. It wasn’t a surprise that it could be used in the treatment of postmenopausal o