Eli Lilly Canada Inc. v. Mylan Pharmaceuticals ULC

Eli Lilly Canada Inc. v. Mylan Pharmaceuticals ULC
Court (s) Database
Federal Court Decisions
Date
2015-01-07
Neutral citation
2015 FC 17
File numbers
T-296-13
Decision Content
Date: 20150107
Docket: T-296-13
Citation: 2015 FC 17
Ottawa, Ontario, January 7, 2015
PRESENT: The Honourable Mr. Justice de Montigny
BETWEEN:
ELI LILLY CANADA INC.
Applicant
and
MYLAN PHARMACEUTICALS ULC AND THE MINISTER OF HEALTH
Respondents
and
ICOS CORPORATION
Respondent Patentee
JUDGMENT AND REASONS
[1] This is an application by Eli Lilly Canada Inc. (Lilly) for an order under section 55.2(4) of the Patent Act, RSC 1985, c P-4, and section 6 of the Patented Medicines (Notice of Compliance) Regulations, SOR/93-133, to prohibit the issuance of a Notice of Compliance (NOC) to Mylan Pharmaceuticals ULC (Mylan) for a generic version of tadalafil, sold by Lilly under the brand name CIALIS, until after the expiration of the Canadian Patent 2,226,784 (the ‘784 Patent).
[2] Mylan, on the other hand, argues that Lilly’s application should be dismissed because the ‘784 Patent is invalid for lack of utility and for obviousness-type double patenting.
[3] For the reasons that follow, I have come to the conclusion that the Applicant has met its burden of proof on the balance of probabilities to establish for the purpose of these proceedings that the ‘784 Patent is valid, and that an order prohibiting the Minister of Health from issuing an NOC should issue.
I. Background [4] Erectile dysfunction, commonly referred to as ED, is a medical condition described as the inability of a man to obtain and maintain an erection sufficiently hard for vaginal penetration and sexual intercourse. ED is an extremely common medical condition believed to affect upwards of 50 percent of men aged 40 to 70.
[5] A muscle is usually considered to be in its resting state when relaxed. In the case of the penis, the reverse is true. The penis contains two symmetrical compartments above and on either side of the urethra, each of which is called a corpus cavernosum. They consist of small blood vessels or passages surrounded by smooth muscle which can contract or relax as with any form of muscle. When constricted, the smooth muscle restricts the flow of blood through the blood vessels in the arterial network entering the corpora cavernosa, acting much like a ligature. Blood exits the corpora cavernosa through veins at approximately the same rate as it enters through the arteries, maintaining the penis in a non-erect state. When an erection is triggered, the smooth muscle surrounding the vessels in the arterial network and the cavernous smooth muscle relax, no longer constricting the arteries delivering blood to the corpora cavernosa. Blood then floods into the highly vascularized tissue of the corpora cavernosa, causing them to swell. That swelling, in turn, squeezes the venules of the membrane enclosing the corpora cavernosa, thereby reducing the size of their internal passages and reducing their ability to drain blood from the corpora cavernosa. The result is that the penis becomes engorged with blood and rigid.
[6] Relaxation of smooth muscle in the penis is therefore a key to the erectile process. What, then, causes smooth muscle to relax and contract? Smooth muscle, which is found in many parts of the body, is under the control of the involuntary autonomic system. Smooth muscle relaxation results from a cascade or series of highly complex biochemical reactions within the body involving chemical messengers operating on communication systems called “pathways”.
[7] By the priority date of the ‘784 Patent, it was known that there are many different pathways that lead to penile smooth muscle relaxation. The pathway to which the Patent is directed is the NO/cGMP pathway. In this pathway, sexual stimulation results in the non-adrenergic non-cholinergic (NANC) nerves releasing nitric oxide (NO). Upon stimulation, the NANC nerves release a flood or rush, of NO. It is known that this flood of NO is primarily responsible for producing an erection.
[8] The nitric oxide diffuses through the cell membrane. Inside the cell, the nitric oxide stimulates guanylate cyclase to convert guanosine triphosphate (GTP) to cyclic guanosine monophosphate (cGMP). An increase in the amount of cGMP inside a smooth muscle cell leads to relaxation of the smooth muscle and eventually to an erection.
[9] A class of enzymes known as phosphodiesterases (PDEs) also regulates the intracellular concentrations of the cGMP. One of these PDEs, PDE V, breaks down the cGMP to its non-cyclic form, GMP. In contrast to cGMP, GMP does not cause smooth muscle relaxation. Tadalafil works by inhibiting PDE V, thereby preventing PDE V from breaking down cGMP to the inactive GMP. Increased concentrations of cGMP then facilitate smooth muscle relaxation.
[10] Tadalafil was initially developed by Drs. Daugan and Grondin and their colleagues at GlaxoSmithKline (Glaxo). It was first disclosed and claimed in Canadian Patent No. 2,181,377 (the ‘377 Patent), which was filed in Canada on January 19, 1995 with a priority date of January 21, 1994. It was published on July 27, 1995. The ‘377 Patent claims novel compounds, including tadalafil, pharmaceutical compositions, and the use of tadalafil in the treatment of various disorders where smooth muscle relaxation was thought to be beneficial, including cardiovascular disorders. This Patent is entitled “Tetracyclic Derivatives, Process of Preparation and Use”.
II. The Impugned Patent [11] The ‘784 Patent was filed in Canada on July 11, 1996, with a priority date of July 14, 1995. It is entitled “Use of cGMP-Phosphodiesterase Inhibitors to Treat Impotence”, and its sole inventor is Dr. Daugan. The ‘784 Patent relates to the use of certain tetracyclic derivatives which are potent and selective inhibitors of PDE V in the treatment of impotence.
[12] According to the specification part of the disclosure, many different drugs have been shown to induce penile erection but are only effective after direct injection into the penis, and are not approved for ED. Current medical treatment involves either injection of vasoactive substances or the use of glyceryl trinitrate patches applied to the penis; while these treatments are effective, they often produce undesirable side effects.
[13] The specification goes on to describe the compounds of the invention (tadalafil and 3-methyl tadalafil), and states that these compounds, “unexpectedly”, have been found to be useful in the treatment of ED. “Furthermore the compounds may be administered orally, thereby obviating the disadvantages associated with i.c. administration” (pp 3-4 of the Patent).
[14] The gist of the invention is described in the following way:
It has been shown that compounds of the present invention are potent and selective inhibitors of cGMP specific PDE. It has now been surprisingly found that human corpus cavernosum contains three distinct PDE enzymes. The predominant PDE has further surprisingly been found to be cGMP PDE. As a consequence of the selective PDE V inhibition exhibited by compounds of the present invention, the subject compounds can elevate cGMP levels, which in turn can mediate relaxation of the corpus cavernosum tissue and consequent penile erection.
(‘784 Patent, p 4)
[15] Oral administration is said to be the “preferred route”, because it is the most convenient and avoids the disadvantages associated with intracavernosal (i.c.) administration, but the drug can also be administered sublingually or buccally. Oral dosages of the compound for curative or prophylactic treatment of ED are said to be in the range of from 0.5 to 800 mg daily, the actual dosing regimen being determined by a physician. For human use, the compounds will be administered in admixture with a pharmaceutical carrier selected with regard to the intended route of administration: “For example, the compound may be administered orally, buccally or sublingually, in the form of tablets containing excipients such as starch or lactose, or in capsules or ovules either alone or in admixture with excipients, or in the form of elixirs or suspensions containing flavouring or colouring agents” (‘784 Patent, p 5).
[16] The ‘784 Patent includes data from two in vitro tests on tadalafil and 3-methyl tadalafil. The first test shows that, when in proximity to the PDE V enzyme, the compounds inhibit its activity. The second test shows that the compounds can penetrate and prolong the cGMP response in rat aortic smooth muscle cells. Taken together, these data indicate that the compounds are potent inhibitors of PDE V in vitro. The Patent also states that the compounds were shown to be highly selective inhibitors of PDE V over other PDE enzymes, but does not provide these data. The ‘784 Patent contains no in vivo testing or clinical studies of any of its compounds.
[17] The ‘784 Patent has 28 claims, which relate generally to pharmaceutical uses of the compounds of the Patent, including use in the treatment of ED. The narrowest claims are limited to tadalafil and 3-methyl tadalafil. Dependent claim 18 is limited to the oral route of administration; other claims provide generally for “treatment”, without being limited to a particular route.
[18] Lilly initially asserted ten claims of the '784 Patent in its Notice of Application. It addressed only claims 2, 4, 12, 14 and 15 in its evidence, and Mylan prepared its evidence accordingly. There is a dispute as to whether Lilly asserts claim 18 as well. After receiving Mylan's evidence, Lilly served reply evidence in which its experts addressed claim 18, and it asserted the claim in its factum. Mylan argues that this attempt to “reassert a withdrawn claim” is improper, but did not provide any evidence to the effect that Lilly had effectively renounced that claim. The fact that both of its experts state in their affidavit that they have been “advised” by counsel to Mylan that only claims 2, 4, 12, 14 and 15 are at issue, is clearly insufficient to establish that Lilly made representations that it was not asserting claim 18. Indeed, Mylan did not strenuously pursue that argument at the hearing.
[19] The claims themselves are reproduced in the Annex. There is no dispute as to the construction of these claims as set out by Lilly.
[20] Claim 2 claims a pharmaceutical composition for the treatment of ED in a male animal comprising a compound selected from the group consisting of two compounds, tadalafil and 3-methyl tadalafil.
[21] Claim 4 relates to the composition of claim 2 for use in human males.
[22] Claim 12 claims the use of tadalafil or 3-methyl tadalafil for the treatment of ED in a male animal. Unlike claims 2, 4 and 15, claim 12 is not limited to a particular pharmaceutical composition but it is still promising that either of the compounds will treat ED in a male animal.
[23] Claim 14 merely adds to claim 12 the element that the male animal is human.
[24] Claim 15 relates to the use of the compositions of claims 2 and 4 for the treatment of ED in a male animal.
[25] Claim 18 may be dependent upon either or both of claims 12 and 14. When one combines claim 18 with both claims 12 and 14, one has a claim to the use of tadalafil or 3-methyl tadalafil in treating ED upon oral administration, including in human males.
III. Issues [26] By letter dated December 21, 2012, Mylan provided a purported Notice of Allegation (NOA) relating to, inter alia, the ‘784 Patent. In its NOA, Mylan alleges that it does not infringe a number of claims in the ‘784 Patent, while other claims are invalid on the basis of lack of utility or, in the alternative, obviousness-type double patenting. As previously mentioned, the relevant claims for the purpose of this application are claims 2, 4, 12, 14, 15 and allegedly 18. As Mylan did not allege non-infringement of these claims, the debate therefore rests entirely on the validity of these claims.
[27] On October 3, 2014, the Applicant filed a motion to strike from the record paragraphs 11-35 and Exhibits 10-33 from the affidavit of Carol Yau, the last two sentences of paragraph 19 and Footnotes 25 and 26 from Mylan’s Memorandum of Fact and Law, and the last sentence of paragraph 106, the quote that follows it, and footnote 159 from Mylan’s Memorandum of Fact and Law. All of these relate to documents alleged to have been filed by Lilly in a European opposition proceeding to a patent relating to VIAGRA sildenafil. At the hearing, I indicated that the motion would be dismissed because the arguments raised go to the weight more than to the admissibility of the documents. I shall now expand briefly on the reasons provided at the hearing.
[28] This matter therefore raises the following issues:
A. Should Lilly’s motion to strike be granted?
B. Is the allegation that the ‘784 Patent is invalid for lack of utility justified?
C. Is the allegation that the ‘784 Patent is invalid for obviousness-type double patenting over the ‘377 Patent justified?
IV. Analysis The burden of proof and the person skilled in the art [29] The parties generally agree as to the legal burden and the person skilled in the art. With respect to the burden of proof, the Court of Appeal stated that the second person must first lead evidence which is sufficient to put the allegations of invalidity “in play” and which is “not clearly incapable of establishing its allegations”: Pfizer Canada v Canada (Health), 2007 FCA 209, at para 109 [Pfizer Apo-Quinapril]. The second person cannot satisfy its initial burden merely by detailing the allegation in the NOA. Once the allegation is in play, the first person is required to meet its burden by proving that the allegation is unjustified on a balance of probabilities: Pharmascience v Canada (Health), 2014 FCA 133, at paras 33-36; Pfizer Canada v Apotex, 2007 FC 971, at para 51 [Pfizer sildenafil], aff’d 2009 FCA 8. If the evidence is evenly balanced, the first person will have failed to prove that the allegation of invalidity is not justified: Eli Lilly Canada v Apotex, 2009 FC 320, at paras 37-40.
[30] As for the person skilled in the art to which the ‘784 Patent is directed, it is agreed between the parties that it is a skilled drug development and discovery team whose members have expertise in chemistry, enzymology, pharmacology, pre-clinical and clinical evaluation of candidate therapeutics, and clinical management of ED. The lead chemistry and pharmacology team members would have a Ph.D. level education, while the clinician(s) would have an M.D. or equivalent. The skilled person has clinical trial experience, as well as knowledge of the physiology of penile erection and the pharmacology of NO, cGMP, and PDE enzymes, including inhibitors of PDE activity, and is familiar with important developments and literature in these areas.
The evidence [31] The parties have submitted voluminous evidence comprised of affidavits and cross-examinations, each with numerous exhibits, including scientific papers and pharmaceutical testing results.
[32] Lilly filed affidavits of two fact witnesses: Dr. Daugan and Dr. Grondin. Lilly also put forth two expert witnesses: Dr. Brock and Dr. Goldstein. Finally, Lilly submitted the affidavit of Cindy Sue Potter, a law clerk, to introduce a number of exhibits including the ‘784 Patent itself, the NOA, and the numerous scientific papers submitted with the NOA. Mylan put forth two expert witnesses: Dr. Murray and Dr. Melman. The affidavits, cross-examinations and exhibits for all these witnesses form part of Lilly’s record. Mylan also submitted the affidavit of Carol Yau introducing several exhibits; by way of a motion to strike, Lilly contests the admissibility of many of these exhibits.
Dr. Daugan [33] Dr. Daugan is a French pharmaceutical researcher (medicinal chemist) with Glaxo, a French pharmaceutical company. He is the listed inventor of the ‘784 Patent. In his affidavit, he describes his involvement in the development of tadalafil, as part of a research project to identify PDE V inhibitors. He recounts that a patent was filed when tadalafil was first developed (international version of the ‘377 Patent), but this patent did not contemplate tadalafil’s use in treating ED. After this patent was filed, and after discussions with colleagues at Glaxo in light of the scientific literature and Phase I clinical trials of tadalafil, he began to consider that tadalafil could be used to treat ED. At this point, the second patent was filed (the international version of the ‘784 Patent). The exhibits to the affidavit are his curriculum vitae, two published papers about the discovery of tadalafil, and lab notebooks.
Dr. Grondin [34] Dr. Grondin is also a researcher for Glaxo. His affidavit describes his role in supervising the in vitro experiments on tadalafil, leading up to the international filing of the ‘784 Patent. Like Dr. Daugan, he describes the decision to file the ‘784 Patent after the researchers predicted that tadalafil – initially developed to treat hypertension – could also be used to treat ED. The exhibits to the affidavit include his curriculum vitae, published papers, and lab notebooks.
Dr. Brock [35] Dr. Brock is a urologist, specialized in erectile dysfunction. He was involved in clinical trials of sildenafil and tadalafil, among other drugs. He consults for many pharmaceutical companies including Eli Lilly. His evidence consists of an affidavit, cross-examination (both with exhibits, primarily scientific papers), and reply affidavit.
[36] In his affidavit, Dr. Brock states that the development of an oral agent for the treatment of erectile dysfunction was an ongoing active area of medical research for decades, prior to the discovery of tadalafil. Sildenafil citrate had been discovered only shortly before the patent for the compound tadalafil (the ‘377 Patent) was filed. Prior to the discovery of sildenafil citrate, the important conceptual limitations were the general belief and understanding that a general vasodilator, while being able to enhance blood flow to the penis, would almost certainly also evoke significant generalized systemic hypotension to the detriment of the individual and, as a consequence, likely be of little clinical utility. Previous experimental work in the area of erectile dysfunction had demonstrated the lack of efficacy of earlier oral agents and the widespread use and acceptance of drugs that were injected directly into the penis was believed to be the gold standard therapy delivery system at the time (1990-1994).
[37] The understanding of the potential therapeutic role of NANC nerve pathway effectors and the identification of PDE inhibitors was also known at that time (July 1995), although it was not known how that might be achieved. Several leading experts had speculated that use of a cGMP PDE inhibitor could be considered for the treatment of erectile dysfunction, but this was not done. The leading research was designed to study the physiological pathways involved in the erectile process; it was not focused on the development of a clinical drug to treat the condition. The experts acknowledged that further research was required before there would be any realistic ability to target a specific mechanism through which erectile dysfunction could be treated. In 1994 and 1995, the leading researchers continued to investigate the use of a nitric oxide donor for the treatment of impotence, as many believed that this would be a better alternative than PDE inhibition.
[38] Therefore further research and investigation were required before one would have been able to predict that the use of a PDE V inhibitor, let alone an orally administered PDE V inhibitor, would be efficacious in the treatment of erectile dysfunction. It was unknown that an orally administered PDE V inhibitor could be effective in treating erectile dysfunction because of the expected systemic effects of administering such a compound orally. According to Dr. Brock, “[t]hat there would exist selectivity in the distribution of PDE enzymes in the penile circulation to a level not found in other essential vascular structures would have been fool-hardy speculation” (Brock affidavit, para 33, Application Record (AR) Vol 2, p 193).
[39] The nature of the ability of a PDE V inhibitor such as sildenafil citrate as a selective PDE V inhibitor to be an effective and safe oral agent for the use of enhancing erectile function in men was fortuitous and insightful. While there was now the idea that PDE V inhibitors could be used clinically, the complete understanding of how best to inhibit cGMP metabolism and augment erectile mechanisms was still in an infantile state. While sildenafil changed the thinking, it did not do so entirely or immediately, as changing scientific theories takes time. Theoretically, any selective and potent PDE V inhibitor could possibly work but one could not say that it was self-evident that it would work, as many characteristics such as metabolism, side effects and absorption of these new agents all needed to be tested.
[40] The inventive concept found in claims 2, 4, 12, 14 and 15 is the treatment of erectile dysfunction using tadalafil or 3-methyl tadalafil. This concept did not appear in the prior art, and Dr. Brock is of the view that a person skilled in the art would not consider the use of tadalafil or 3-methyl tadalafil to be obvious. It would be inventive, because:
[o]ne of skill in the art would have reason to hope that either compound could be used to treat erectile dysfunction, particularly in light of the publication of the patent claiming the use of sildenafil citrate for the same use, but it would not reach the level of self-evident that either compound would be successful in treating erectile dysfunction or that the person of skill in the art would consider that either compound ought to work to treat erectile dysfunction.
(Brock affidavit, para 38, AR Vol 2, p 194)
[41] Finally, Dr. Brock determined that the promise of the ‘784 Patent is the treatment of erectile dysfunction. In his view, a person skilled in the art would consider this promise to be soundly predicted based on the information disclosed in the Patent and the common general knowledge, and there was sufficient information available with respect to PDE V inhibitors and particularly sildenafil citrate, to allow the inventor to predict the use of potent and selective PDE V inhibitors like tadalafil and 3-methyl tadalafil in the treatment of ED.
[42] In his reply affidavit, Dr. Brock addresses Mylan’s construction of the promise, namely that the disclosed tetracyclic derivatives (tadalafil or 3-methyl tadalafil) will be effective in treating erectile dysfunction when administered orally. In his view, the person skilled in the art would not view the promise of the Patent as a whole so narrowly. That the compounds may be administered orally is only one aspect of the invention. That being said, he believes that the ‘784 Patent is still soundly predicted if it is found that the promise of the Patent as a whole relates to oral administration.
Dr. Goldstein [43] Dr. Goldstein is also a urologist, specialized in sexual dysfunction. He was involved in clinical research involving sildenafil and tadalafil, among other drugs. He has also served as an expert witness for Pfizer in VIAGRA sildenafil litigation.
[44] He states that in 1994, no effective oral therapy for ED was available prior to sildenafil. The “gold-standard” drug treatment for ED in 1994 did not involve oral pills but did involve the injection of vasodilator drugs into the corpus cavernosum. Vasodilator medications in 1994 could not be administered systemically (e.g. orally) for the treatment of ED, as this led to smooth muscle relaxation throughout the vasculature and serious hypotension could result. Systemic vasodilation, a common mechanism of oral antihypertensive drugs, actually causes ED rather than treats it.
[45] In 1994, penile erection was known to occur after smooth muscle relaxation of the penis. The neurologic system, including the NANC nerves, the central nervous system, and the peripheral nervous system were, in part, implicated in affecting penile erection. It was also known that a number of chemical messengers, including nitric oxide, were involved in the biological processes affecting local penile smooth muscle tone. In 1994, it was also known that the vascular system and the endocrine system were in part affecting penile erection.
[46] Dr. Goldstein also states that a handful of basic science groups were examining the mechanism of action of nitric oxide/cGMP on smooth muscle relaxation in penile tissue, but it had not been demonstrated conclusively that nitric oxide was the NANC transmitter to the exclusion of other NANC vasodilator substances. Research was focussed primarily on increasing the production of cGMP with nitric oxide donors. There was minimal research on preventing the degradation of cGMP within the cell (PDE inhibitors). Moreover, the distribution of PDE enzymes in the corpus cavernosum was not known publicly until 1999.
[47] Finally, Dr. Goldstein indicates that the publication of Pfizer’s patent on the use of sildenafil and related compounds as treatments for impotence in December 1994 was the first public disclosure of an invention claiming that a PDE inhibitor, taken orally and present systemically, could effectively treat erectile dysfunction in men. The mechanism of the preferential therapeutic activity for sildenafil and related compounds was not fully understood until a study examining the selective tissue distribution of PDE V was published in 1999. Therefore, “the claims for sildenafil in Pfizer’s 1994 patents served as a prototype for an orally active therapy for the treatment of ED, but did not yet provide a rational basis for the development of other selective PDE V inhibitors. Further, the potency, selectivity, and safety of other compounds with chemical structures unrelated to sildenafil could not have been predicted in 1994” (Goldstein affidavit, para 16, AR Vol 2, pp 275-276). He concludes that the claims of the ‘784 Patent are novel and inventive over the claims of the ‘377 Patent.
[48] In his view, the promise of the ‘784 Patent is that either of the compounds, tadalafil or 3-methyl tadalafil, can be used to treat erectile dysfunction. He finds that this promise is soundly predicted at the filing date based on testing disclosed in the Patent and the advances in the field up to 1996.
[49] In his reply affidavit, he addressed the alternative promise put forward by Mylan, namely that tadalafil or 3-methyl tadalafil will be effective in treating ED upon oral administration. In his view, a person skilled in the art would not consider this to be the promise of the Patent; the invention as claimed is not that narrow, except for claim 18. Even if the promise was to include oral administration, he remains of the view that the invention is soundly predicted.
Dr. Murray [50] Dr. Murray is a clinical pharmacologist. He is a professor of medicine and pharmacology and a clinical researcher.
[51] According to Dr. Murray, the skilled person in the art would consider the promise of the ‘784 Patent to be that tadalafil or 3-methyl tadalafil will be effective in treating ED upon oral administration, including in human males. Demonstration of that promise would require efficacy and toxicity data from oral dosing in humans, and such testing had not been conducted by the ‘784 filing date.
[52] Moreover, the promise of oral effectiveness could not have been soundly predicted by the skilled person in the art at that time. The only data in the ‘784 Patent pertain to in vitro potency of tadalafil and 3-methyl tadalafil in inhibiting the PDE V enzyme, which was known to be involved in the erectile process:
[t]here is no testing of the compounds in corpus cavernosum tissue from any species, nor are there any in vivo data on whether the compounds could be adequately absorbed across the gastrointestinal barrier, or whether they could sufficiently distribute to, and penetrate into, the penis before being metabolized and/or excreted by the body.
(Murray affidavit, para 19, AR Vol 10, pp 1752-53)
[53] There are also no data on whether an effective oral dose could be achieved that was not so high as to cause unacceptable side effects in other tissues. Moreover, no inferences could be drawn from the fact of sildenafil having been successfully orally administered because sildenafil is chemically distinct from tadalafil and 3-methyl tadalafil.
[54] In contrast, the use of tadalafil to treat ED by direct injection would have been obvious to the skilled person in the art at the ‘784 Patent priority date in light of the ‘377 Patent claims. It was known that PDE V inhibitors enhanced the erectile process if sufficient concentrations could be achieved in the corpus cavernosum, and since direct injection bypasses potential problems associated with absorption and distribution and often allows lower dosing to avoid systemic toxicities, a skilled person would have a reasonable expectation of success in using tadalafil in this way.
Dr. Melman [55] Dr. Melman is a professor of urology and a physician. As part of his practice, he administers sildenafil, tadalafil, and other drugs to patients with ED.
[56] He is also of the view that a skilled person would understand the ‘784 Patent to be promising that tadalafil and 3-methyl tadalafil are effective for treatment of ED in humans, including by oral administration. As of the filing date of the ‘784 Patent, the inventors had tested these two compounds in in vitro assays, and tadalafil had additionally been tested by oral administration in an in vivo model of hypertension in rats. However, no testing had been conducted to evaluate the therapeutic efficacy of the compounds in humans with ED. As such, the promise of the Patent had not been demonstrated.
[57] Dr. Melman adds that the promise had not been soundly predicted as of the ‘784 filing date. The two in vitro tests disclosed in the ‘784 Patent did not provide a sufficient factual basis for a prediction of therapeutic utility on oral administration to humans with ED. For a skilled person to make any prediction of a therapeutic effect in ED on oral administration, he or she would need some information about the absorption, metabolism and tissue distribution of the compounds in question when orally administered. No such information is provided in the ‘784 Patent, and as such, the skilled person cannot draw any meaningful inferences as to the efficacy or safety of the compounds on oral administration.
[58] Finally, Dr. Melman states that, in light of the claims of the ‘377 Patent, it would have been obvious at the ‘784 priority date that tadalafil would be useful in the treatment of ED if administered by intracavernosal injection. The ‘377 claims are premised on tadalafil’s activity as a selective PDE V inhibitor, and this same biochemical activity forms the basis for the ‘784 relevant claims to therapeutic use in ED. Because intracavernosal administration would ensure delivery of the compound to the target tissue, many of the pharmacokinetic concerns relevant to oral administration would be alleviated. Therefore, the skilled person would have a reasonable expectation that tadalafil would work to treat ED by this route of administration.
A. Should Lilly’s motion to strike be granted? [59] In its NOA, Mylan referenced and quoted excerpts from documents alleged to have been filed by Eli Lilly and Company (the parent corporation of Lilly) and ICOS in a European opposition proceeding to a patent relating to VIAGRA sildenafil. Mylan thereby attempted to rely on purported admissions made by Eli Lilly and Company and ICOS in the section of its NOA relating to obviousness-type double patenting. In its Notice of Application, Lilly denied that any admissions were made, or that these documents and statements within them were relevant to this proceeding.
[60] Lilly did not comment on these documents in its evidence, and neither did Mylan. Mylan merely attached them to an affidavit of its law clerk, Carol Yau, and included it in its evidence served on Lilly on December 6, 2013. Lilly did not voice any objection to that affidavit, and did not examine Ms. Yau. However, Lilly excluded the Yau affidavit and its exhibits from its Application Record.
[61] Mylan included the Yau affidavit in its Responding Application Record, which was served and filed on August 22, 2014. Lilly did not see fit to bring its motion to strike until October 3, 2014, six business days before the hearing of this Application. According to Lilly, these documents have been improperly introduced into evidence, are not relevant to any issue in this proceeding, and constitute hearsay.
[62] This Court has repeated on more than one occasion, that the discretion to strike affidavits or portions thereof should be exercised sparingly and only where it is in the interests of justice to do so: see e.g. Armstrong v Canada (Attorney General), 2005 FC 1013, at para 40.
[63] It is no doubt true that merely attaching a document to an affidavit is generally not proof of a document: Inhesion Industrial Co v Anglo Canadian Mercantile Co (2000), 6 CPR (4th) 362 (FCTD), at para 22. At the end of the day, however, the test for authentication of documentary evidence is that the trier of fact be satisfied that the document in issue is what it purports to be: Sopinka, Lederman & Bryant, The Law of Evidence in Canada, 4th ed (Markham, Ont: LexisNexis, 2014) at para 18.6.
[64] The impugned documents purport on their face to have been filed with the European Patent Office (EPO), by or on behalf of Eli Lilly and Company and/or ICOS. They appear to be listed on the Register in relation to European Patent 0 702 555 (EP 555) and the affidavit included particulars as to the date each document was listed and the way in which it was described on the Register.
[65] Despite speculative submissions by Lilly to the effect that the documents may not be complete copies and may not form a “complete picture” of the record on the opposition, there is no reason to doubt the authenticity and accuracy of the impugned exhibits. Lilly has offered no evidence that the documents are incomplete, modified or anything other than what they purport on their face to be. The Register is a matter of public record, and Lilly could have determined if the documents were true and complete copies. It was also open to Lilly to call witnesses with first-hand knowledge of the impugned documents, either to question their authenticity or to explain the statements made in them. The evidence is that they were authored by the parent company of Lilly, and as the Supreme Court noted in Evans, “a party can hardly object that he had no opportunity to cross-examine himself”: R v Evans, [1993] 3 SCR 653, at 664. As for Lilly’s argument that Mylan could have introduced the impugned documents pursuant to section 23 of the Canada Evidence Act, RSC 1985, c C-5, it is of no merit. That provision allows for the evidence of any proceeding or record to be given by way of exemplification or certified copy if it originates from courts in Canada, Great Britain, the United States “or of any other foreign country”. No argument has been presented in support of the proposition that the EPO is a court of record of a foreign country. In any event, it is clear that section 23 of the Canada Evidence Act is not the only procedure by which foreign evidence can be proven, and Lilly has not successfully impugned the authenticity of the material to which it now objects.
[66] Lilly also argued that the documents in question are not relevant to any issue in this proceeding. They relate to a different type of proceeding unknown in Canada, to revoke a different patent on a different basis than the allegations made by Mylan in this proceeding. There is no doubt that the Court is not bound by the decisions of foreign courts dealing with corresponding patents, to say nothing of different patents. As this Court stated in Eli Lilly v Apotex, 2007 FC 455, at para 244 (aff’d 2008 FCA 44):
This Court is not bound by the decisions of foreign courts dealing with corresponding patents. In the words of the Federal Court of Appeal: “Although foreign patents may be practically identical, foreign law is unlikely to be so and must, in any case, be proved” (Lubrizol Corp. v Imperial Oil Ltd. (1992), 45 C.P.R.(3d) 449). These words are especially apt in the present matter which can be differentiated from what occurred in the United States on a number of grounds, including the nature of the proceedings, the evidence, and the burden of proof.
[67] That being said, the evidence offered by Mylan is not relied upon to establish a point of law, but only to show that Lilly’s previous statements with respect to the state of the common general knowledge regarding ED and its treatment in the early 1990s, are inconsistent with the position it is now taking. These statements would be insufficient to establish that the ‘784 Patent is invalid for obviousness-type double patenting, not only because European patent law differs from Canadian patent law but also because they were not meant to be a conclusion of law but the expression of a factor to be taken into consideration in applying the applicable legal test in the EPO. In other words, Mylan is referring to these statements not for the truth of their content, but for the fact that they were made. To that extent, they are not inadmissible as hearsay evidence and they are relevant to Mylan’s allegation of obviousness-type double patenting.
[68] The weight to be given to these statements in assessing the reliability of Lilly’s evidence with respect to the state of the common general knowledge at the relevant date, and with respect to the inference that could be drawn at the time from prior art documents, is obviously another matter. For the reasons advanced by counsel for Lilly (different patent, different type of proceeding, different applicable legal principles), caution must be exercised when importing into a proceeding submissions made in a different context. Indeed, this Court does not even know how the EPO ruled on these submissions.
[69] For all of the foregoing reasons, I find that Lilly’s motion to strike ought to be dismissed. This is not to say that the impugned statements should carry the same weight as if they had been made by Lilly itself in a prior Canadian proceeding involving the same patent. Accordingly, the documents sought to be struck by Lilly will remain part of the evidence, but will be given the weight commensurate to the circumstances and the legal context in which they were drafted.
B. Is the allegation that the ‘784 Patent is invalid for lack of utility justified? [70] Utility is part of the definition of “invention” in section 2 of the Patent Act, which states that the claimed art must be “useful”. A patent’s utility must therefore either be demonstrated or soundly predicted at the filing date, when the new use is the essence of the invention: Apotex Inc v Wellcome Foundation Ltd, 2002 SCC 77, [2002] 4 SCR 153, at para 56 [AZT]; Eli Lilly Canada v Novopharm Ltd, 2010 FCA 197, at para 74 [Olanzapine]; Pfizer Apo-Quinapril, above, at para 153.
[71] The promise of a patent is fundamental to the utility analysis and must be ascertained at its outset. Promised utility is an aspect of claims construction, and is therefore a question of law: Apotex v Bristol-Myers Squibb Co, 2007 FCA 379, at para 27; Olanzapine, above, at para 80. The promise is construed in the context of the patent as a whole, through the eyes of the person skilled in the art, and in relation to the science and information available at the filing date: Olanzapine, above, at paras 80, 93. The promise must also be interpreted consistently with the inventive concept: Hoffman-La Roche Ltd v Apotex, 2011 FC