Pfizer Canada Inc. v. Ratiopharm Inc.

Pfizer Canada Inc. v. Ratiopharm Inc.
Court (s) Database
Federal Court Decisions
Date
2010-06-08
Neutral citation
2010 FC 612
File numbers
T-955-08
Decision Content
Federal Court
Cour fédérale
Date: 20100608
Docket: T-955-08
Citation: 2010 FC 612
Ottawa, Ontario, June 8, 2010
PRESENT: The Honourable Mr. Justice Kelen
BETWEEN:
PFIZER CANADA INC. and
PFIZER INC.
Applicants
and
RATIOPHARM INC. and
THE MINISTER OF HEALTH
Respondents
PUBLIC
REASONS FOR ORDER AND ORDER
[1] This is an application for an Order under the Patented Medicines (Notice of Compliance) Regulations, SOR/93-1333 (the NOC Regulations), prohibiting the Minister of Health from issuing a Notice of Compliance to Ratiopharm for a generic version of REVATIO until Pfizer's Canadian Patent 2,324,324 (hereafter the '324 Patent) expires in 2014. Ratiopharm alleges that Pfizer's patent for REVATIO is invalid for lack of soundly predicted utility, obviousness, and anticipation so that the generic version of REVATIO should immediately be allowed on the Canadian market.
TABLE OF CONTENTS
Paragraph Number
BACKGROUND............................................................................................................... [2]
ANALYSIS
Burden of Proof.................................................................................................... [62]
Patent Claim Construction..................................................................................... [63]
ISSUE NO. 1:
Is the ‘324 Patent entitled to a priority date claim based on GB 970?..................... [79]
ISSUE NO. 2:
Is the ‘324 Patent invalid for lack of sound prediction?........................................... [91]
ISSUE NO. 3:
Is the ‘324 Patent invalid for obviousness in view of the prior art?........................... [98]
CONCLUSION............................................................................................................. [183]
BACKGROUND
The ‘324 Patent
[2] The '324 Patent claims the use of sildenafil in the treatment of pulmonary hypertension. The applicant Pfizer Ireland Pharmaceuticals, owns the '324 Patent, and the applicant Pfizer Canada Inc., markets the drug sildenafil citrate in Canada under the trade name REVATIO.
[3] The applicants obtained the '324 Patent on December 20, 2005, from an application filed in Canada on October 26, 2000 which claimed priority from Great Britain Patent Application No. 9925970.7 filed on November 2, 1999. The '324 Patent will expire on October 26, 2020.
[4] The ‘324 Patent claims the use of sildenafil or preferably sildenafil citrate for treating or preventing pulmonary hypertension. The ‘324 Patent claims are set out in Appendix 1 to these Reasons.
The Parties
[5] The applicant Pfizer Canada Inc. is the Canadian operation of the multinational pharmaceutical company Pfizer Inc., which manufactures REVATIO. The applicant Pfizer Ireland Pharmaceutical owns the patent, and Pfizer Canada is a licensee under the patent.
[6] The respondent Ratiopharm Inc. filed an Abbreviated New Drug Submission (ANDS) with Health Canada on April 2, 2008 in respect of Sildenafil Citrate Tablets, 20 mg, for oral administration. The ANDS compared the Ratiopharm tablets with the applicants' REVATIO Sildenafil Citrate Tablets, 20 mg. The Ratiopharm tablets are indicated for the “treatment of primary pulmonary arterial hypertension (PPH) or pulmonary hypertension secondary to connective tissue disease, in patients with WHO functional class II or III who have not responded to conventional therapy”. Ratiopharm served its Notice of Allegation, alleging the invalidity of the ‘324 Patent, on Pfizer on May 1, 2008.
[7] The respondent the Minister of Health did not participate in this application, as is normally the case in such proceedings.
Pulmonary hypertension
[8] Pfizer describes pulmonary hypertension in the affidavit of its witness, Dr. Ghazwan Saleem Butrous, sworn on September 5, 2008 at paragraphs 8 and 11:
¶8 Pulmonary hypertension is a cardiovascular disease that ultimately affects the heart. In the body, there are two separate circulatory systems, both of which originate and terminate in the heart…The pulmonary circulatory system…is largely located within the lungs, and plays a crucial role in transporting blood and oxygen between the heart and the lungs. Put at its simplest, pulmonary hypertension is a lung disorder where the pressure in the blood vessels that lead from the heart to the lungs rises above normal levels…
[…]
¶11 Pulmonary hypertension is characterized by the constriction or tightening of the blood vessels connected to and within the lungs. This in turn leads to increased resistance in the blood vessels, which, in turn, causes the pressure in the blood vessels to increase. As a result of the increased resistance and pressure, it becomes harder for the heart to pump blood through the lungs…This can eventually lead to heart failure (and in particular, “right heart” failure)…
[9] While commonly referred to as a “disease”, pulmonary hypertension is in fact a rare blood vessel disorder of pulmonary circulation (also described as a hemodynamic abnormality) whereby the pulmonary arteries or veins constrict and the wall of the arteries thicken, making it more difficult to pump out blood from the heart’s right ventricle because the pulmonary arterial pressure rises above normal levels. Patients suffering from pulmonary hypertension will experience shortness of breath with minimal exertion, fatigue, dizzy spells and fainting.
[10] The causes of pulmonary hypertension are not fully understood but current research indicates that it can be caused by any number of chronic, acute or pathological diseases.
[11] Left untreated, the elevated pressure in the heart’s right ventricle will damage the heart’s muscles, lead to dysfunction, and ultimately heart failure and death within two to three years, often in young adults between the ages of 20 and 30.
[12] Pulmonary hypertension was traditionally classified as “primary” (also known as idiopathic or unexplained) and “secondary”, the first being a diagnosis made possible after all known secondary causes of pulmonary hypertension were ruled out. In recent years the knowledge of pulmonary hypertension has expanded, leading to the abandonment of the old classification system. The new “Evian” system for classifying pulmonary hypertension is named after the location of the conference in France where it emerged.
How sildenafil treats pulmonary hypertension
[13] Sildenafil decreases the resistance in the pulmonary blood circulation system by causing smooth muscle relaxation. Patients feel better and less damage is caused to their hearts when their vascular resistance is reduced on a long term basis with sildenafil.
[14] The best measure of pulmonary hypertension is vascular resistance, determined by reference to Pulmonary Vascular Resistance (PVR), and Systemic Vascular Resistance (SVR). These measurements are obtained by conducting a “right heart catherization” on pulmonary hypertension patients. The formula for calculating PVR is as follows:
The formula for calculating SVR is as follows:
The goal in treating pulmonary hypertension patients is to lower their PVR by decreasing the pressure in the pulmonary arteries and increasing the volume of blood pumped by the heart. The PVR should be reduced to a greater degree than the SVR for the treatment to be effective and safe. A drop of more then 10% in SVR is considered unsafe.
[15] As I discussed in Pfizer Canada Inc. v. Novopharm Ltd., 2009 FC 638, 76 C.P.R. (4th) 83 [from henceforth referred to as my “VIAGARA decision”], Sildenafil was initially developed by Pfizer in the mid-1980s as one of a number of compounds for the treatment of hypertension and angina, cardiovascular conditions in which smooth muscle cells are implicated. The heart’s tissue is made up of small blood vessels or passages surrounded by smooth muscle which can contract or relax, as with any form of muscle.
[16] I discussed the effect of sildenafil on the penis tissue in men who suffer from erectile dysfunction [“ED”] in my VIAGRA decision at paragraphs 10-12:
¶10 Sildenafil inhibits a chemical in the body known as PDEV, which otherwise stops the blood from flowing into the penis and causing an erection.
¶11 Many different cascades of first and second messages, known as "pathways," were known in 1993 to relax or contract smooth muscle tone in the penis. These included the non-adrenergic non-cholinergic (or NANC) pathway. It is now known, although it was not known in 1993, that sildenafil treats ED by virtue of its effects on the NANC pathway in which the first messenger is nitric oxide (NO), and the second messenger is cGMP, which is regulated by PDEV.
¶12 Sildenafil was initially developed by Pfizer in the mid-1980s as one of a number of compounds for the treatment of hypertension and angina, cardiovascular conditions in which smooth muscle cells are implicated. Because sildenafil is a potent and selective cGMP PDE inhibitor, it is able to treat ED in men through the operation of the NO-cGMP pathway.
[17] It was known at the time of the invention of VIAGRA that PDE5 rich tissue could be found not only in the penis but also in the heart and pulmonary system. The heart’s tissue is made up of small blood vessels or passages surrounded by smooth muscle which can contract or relax, as with any form of muscle.
[18] Because sildenafil is a potent and selective (“cGMP PDE5”) inhibitor, it causes elevated levels of cGMP messengers which in turn lead to smooth muscle relaxation in certain tissue. These tissues have a high concentration of PDE5. In other words, sildenafil selectively lowers PVR to a greater degree than SVR and consequently reduces the hemodynamic abnormality in pulmonary hypertension patients. Or in plain English, sildenafil causes smooth muscle relaxation which allows the blood to flow with less resistance between the heart and the lungs.
THE EVIDENCE
Pfizer
[19] Pfizer has provided affidavits from two of its employees and two expert witnesses:
Pfizer Employees
1. Dr. Ghazwan Saleem Butrous
2. Mr. Ian Machin
Pfizer Experts
3. Dr. Lewis J. Rubin
4. Dr. John Granton
Dr. Butrous’ evidence regarding his discovery of sildenafil for the treatment of pulmonary hypertension
[20] Dr. Butrous is one of the inventors named in the ‘324 Patent. He is a cardiologist. He holds the position of Senior Director and Chief Scientific Officer for the Respiratory and Allergy Therapeutic Area at Pfizer in the United Kingdom.
[21] Dr. Butrous begins by explaining the condition of pulmonary hypertension and sets out the following five classes of this condition which were accepted in 1998 as the Evian Classification System, and are used to classify the clinical study patients in the ‘324 Patent. See paragraph 15 of his first affidavit dated September 5, 2009:
1. pulmonary arterial hypertension, which includes both primary and some secondary cases;
2. pulmonary venous hypertension, including patients with congestive heart failure;
3. patients with pulmonary hypoxic hypertension, including patients with chronic obstructive pulmonary disease;
4. patients with pulmonary thromboembolism (a blood clot in the lungs); and
5. a miscellaneous category.
[22] In May 1998 Dr. Butrous was approached by Mr. Steve Felstead, the Director of Clinical Research for Pfizer at the time, and asked to look into alternative uses for sildenafil in the cardio-vascular system. Sildenafil at the time was used to treat erectile dysfunction under the brand name VIAGRA. Dr. Burous explains Pfizer’s interest in sildenafil at paragraph 16:
¶16 …Sildenafil began its life as a cardio-vascular drug (for angina), before Pfizer learned that it could be used for erectile dysfunction. Pfizer therefore continued to be interested in its use for related purposes.
[23] Dr. Butrous states at paragraph 19 that he hypothesized, from his knowledge of the way sildenafil worked in treating erectile dysfunction, that sildenafil could potentially be used to elevate levels of cGMP in the blood vessels in the lungs, which would in turn lead to smooth muscle relaxation and reduce the symptoms of pulmonary hypertension. However, the lack of knowledge with respect to the location of PDE5 in the lungs, the role of PDE5 in pulmonary hypertension patients, and the lack of knowledge of the effect of sildenafil on the systemic vasculature meant that it was not possible without clinical testing to determine whether sildenafil could in fact be used to treat pulmonary hypertension patients. Dr. Butrous began work on a proposal to use sildenafil to treat pulmonary hypertension around May and June 1998.
[24] A clinical study was developed by the end of 1998 to determine the effect an intravenous administration of sildenafil had on PVR in pulmonary hypertension patients. This was the 1024 Clinical Study (1024 study).
[25] The 1024 study ran from January 7, 2000 to January 29, 2002. The following are the key features of the 1024 study:
[CONFIDENTIAL EVIDENCE REFERRED TO HAS BEEN REDACTED FROM THE PUBLIC VERSION OF THE REASONS FOR ORDER ______________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________
________________________________________________________________________________________ _______________________________________________________________________________________________________ __________________________________________________________________________________________________________________________]
all patients were given Nitric oxide (“NO”) before being administered sildenafil. Dr. Butrous theorized that if the NO did not reverse the patients’ pulmonary hypertension then neither would sildenafil; hemodynamic measurements were collected to ascertain the patients’ PVR and SVR through heart catheterization before any treatment, after NO was administered, and after sildenafil was administered; the protocol required that patients withdraw from the study if they experienced a drop of more then 10% in their SVR; sildenafil was administered in small doses of 100, 300 and 500 nanograms per millilitre of plasma for 20 minutes each (which roughly corresponds to orally administered doses of 25, 50 and 100 mg respectively); 3 out of the 12 patients in Group 1a were given placebos, as well as 3 out of 10 patients in group 1b. All 6 patients in Group 2 received sildenafil; and the preliminary results showed that sildenafil reduced PVR while SVR was not affected and sildenafil did not appear to be dose dependant to be effective.
[26] Dr. Butrous only received the interim results from Group 1a before the patent application was filed on October 26, 2000. The August 2, 2000 results of the 1024 study indicated that sildenafil caused a decrease in PVR of 23.7%, 27.9%, and 32.6% at the three dosage levels while SVR decreased by 14%, 17%, and 14% respectively. These results led Pfizer to the following conclusions:
1. sildenfial is effective in controlling the pulmonary pressure;
2. it has a greater effect on the pulmonary circulation versus the systemic circulation;
3. it is not dependant on NO; and
4. it is safe.
[27] The 1024 study Report, attached to Dr. Butrous’ affidavit, states the overall conclusion of the study as follows at page 68:
IV sildenafil showed a general trend to reduce PVR in subjects with pulmonary hypertension. This was not seen on placebo. Proportionally, the decrease in PVR was greater than the decrease in SVR for all groups.
[28] Dr. Butrous clarified that the ‘324 Patent was filed on the basis of the interim results of the 1024 study, which only included a portion of the results in Group 1a, and none in the other two groups. Dr. Butrous maintains that he was able to demonstrate the utility of the ‘324 Patent from the data he had acquired by July 2000.
Mr. Machin’s evidence regarding his discovery of sildenafil for the treatment of pulmonary hypertension
[29] Mr. Machin is one of the inventors named in the ‘324 Patent. He received a B.Sc. in pharmacology from the University of Leeds in 1977. Mr. Machin has been employed since 1980 by Pfizer Global Research and Development where currently he holds the position of Director in the Pain TA in Discovery Biology in the United Kingdom. His first affidavit was sworn September 5, 2008.
[30] In February 2000 Mr. Machin conducted, on behalf of Pfizer, a study to determine the effects of intravenously administered sildenafil on hypoxic pulmonary vasoconstriction (“HPV”) in 6 out of 10 anaesthetized dogs. The purpose of the study was to study the effects of sildenafil on artificially induced conditions of acute pulmonary hypertension in dogs which was induced by adding nitrogen to a gas mixture to the point where oxygen levels decreased from 40% to 10%.
[31] The study demonstrated a greater decrease in PVR than in SVR in response to the administration of sildenafil in various doses.
.
[32] Dr. Machin conceded that the pulmonary vasodilator is widely accepted as having value in treating human patients suffering from pulmonary hypertension. Accordingly, the dog study was “carried out in order to support the exploration, examination, of whether sildenafil could be used to treat pulmonary hypertension”.
Dr. Rubin’s evidence regarding the ‘324 Patent
[33] Dr. Rubin is a Professor of Medicine at the University of California, San Diego School of Medicine and expert in the treatment of pulmonary hypertension. He obtained his medical degree from the Albert Einstein College of Medicine in 1975. His affidavit was sworn on May 22, 2009.
[34] Dr. Rubin addresses the allegation of invalidity of the ‘324 Patent, the claim date of the ‘324 Patent, and construing certain terms in the ‘324 Patent.
[35] Dr. Rubin starts by stating that a veterinarian or pharmaceutical formulator are not persons skilled in the art because the ‘324 Patent is directed to the treatment of humans and the invention is not a formulation of chemistry, but rather a treatment for a disease.
[36] In paragraphs 43-44, Dr. Rubin states that in his view the ‘324 Patent claims the use of sildenafil to treat pulmonary hypertension alone, and not in combination with other therapies or substances.
[37] Dr. Rubin states at paragraph 50 that much of the prior art cited by the respondent would not have been sought out and found by a person involved in diagnosing and treating patients with pulmonary hypertension.
[38] Dr. Rubin then addresses the prior art which was described in Dr. Waxman’s affidavit.
[39] With respect to Weimann et al, Dr. Rubin rejects at paragraphs 55-56 of his affidavit the applicability of the sheep study to pulmonary hypertension:
¶55 The only thing this abstract discloses is that sildenafil (a vasodilator) lowers the PVR in sheep that were administered U46619 (a vasoconstrictor). The Weimann abstract does not disclose the invention claimed in the 324 Patent. The invention claimed in the 324 Patent is not the use of sildenafil in treating conditions of acute vasoconstriction. Rather, the invention is the use of sildenafil in the treatment of the disease of pulmonary hypertension. Pulmonary hypertension is not the same thing as pulmonary vasoconstriction. These two terms are neither synonymous nor interchangeable. Just because you treat artificial vasoconstriction, does not mean you have treated the disease of pulmonary hypertension.
¶56 Furthermore, the animal model used by Weimann is just that: an animal model. Weimann does not show that sildenafil can be used to treat humans. This animal model cannot be considered analogous to any disease state, including pulmonary hypertension, in humans…
[40] Dr. Rubin dismisses the balance of the journal articles and patents because they are either based on subjects who are not pulmonary hypertension patients, are dated after the claim date of the ‘324 Patent, or discuss PDE5 inhibitors and sildenafil in general, or they are focused on the treatment of ED. They therefore do not constitute prior art.
[41] Dr. Rubin conceded in his cross-examination, dated October 21, 2009, that if the claim date is October 26, 2000, Abrams anticipates the patent. (I have not referred to this article because I find later in these Reasons that the priority date is November 2, 1999. If I am wrong, then the parties agree that the ‘324 Patent was anticipated by the Abrams article.)
[42] Dr. Rubin acknowledged that Weimann et al., performed the sheep study to further the potential treatment of humans for pulmonary hypertension, but maintained that it would be inappropriate to take the observations of Weimann in sheep with induced acute vasoconstrictions and apply that to human patients without any human studies for safety.
Dr. Granton’s evidence regarding the ‘324 Patent
[43] Dr. Granton is an Associate Professor of Medicine at the University of Toronto, consultant in pulmonary and critical care medicine at the University Health Network and Mount Sinai Hospital and the Director of the Pulmonary Hypertension Program at Toronto General Hospital. He received his medical degree from McMaster University in 1987. He swore his first affidavit on June 19, 2009 and a second affidavit in Sur-Reply on September 1, 2009.
[44] Dr. Granton considers the “art” in the ‘324 Patent to be the treatment of patients with pulmonary hypertension. Therefore the person skilled in the art is a practicing physician specializing in the treatment of pulmonary hypertension which may include a pulmonologist, cardiologist, or a critical care specialist.
[45] Dr. Granton states that the ‘324 Patent is directed towards “pathological pulmonary hypertension”, as listed by the Evian classification system and not the acute manifestations of pulmonary hypertension resulting from temporary causes such as surgery. The reason for the distinction is that many forms of acute pulmonary hypertension were not in desperate need for new medication such as their pathological counter parts because they could be effectively treated with NO for short term purposes. Accordingly, the person skilled in the art would not consider that the claims of the ‘324 Patent relate to the various acute conditions caused by vasoconstriction, listed in page 9 of the Patent, which include for example dizziness or shortness of breath.
[46] Dr. Granton then addresses the prior art and concludes that it does not disclose the invention in the ‘324 Patent.
[47] Dr. Granton stated in his cross-examination, dated September 12, 2009, (page 2582 of applicants’ record) that before the disclosure of the ‘324 Patent, there is no other document, including the priority UK patent application, which would allow you to make a sound prediction.
[48] Dr. Granton states that he could not, by reference only to the ‘324 Patent, make a sound prediction that sildenafil is effective in treating chronic pulmonary hypertension, without reading more details about the 1024 study.
[49] With respect to the prior art, Dr. Granton states that they are either based on animal models which only provide hypothetical support for the invention, or they relate to very acute situations which do not translate to knowledge about the treatment of chronic pulmonary hypertension.
Ratiopharm
[50] Ratiopharm has provided affidavits from two experts:
Experts
1. Dr. Aaron Waxman
2. Dr. Gregory Elliott
Dr. Waxman’s evidence regarding the ‘324 Patent
[51] Dr. Waxman is an Assistant Professor of Medicine, Pulmonary and Critical Care Unit at the Harvard Medical School and an attending physician at Massachusetts General Hospital in Boston. He obtained his medical degree in 1992 from Yale University. Dr. Waxman is a certified pulmonologist. His first affidavit was filed on February 17, 2009.
[52] In construing the meaning of the term “pulmonary hypertension”, Dr. Waxman states that the persons skilled in the art are practicing physicians or veterinarians specialized in the treatment of pulmonary hypertension and pharmaceutical formulators involved in the development of pulmonary hypertension medicines. The person skilled in the art would have regard to the following paragraph in page 9 of the ‘324 Patent:
Compounds of the invention can also be used to treat children who have pulmonary hypertension post operatively or due to respiratory distress syndrome or neonatal hypoxia.
Dr. Waxman therefore concludes at paragraph 38 of his affidavit that the ‘324 Patent is not limited to chronic disease states. Rather, the disclosure indicates that that the inventors intended to include any type of pulmonary hypertension.
[53] Dr. Waxman states at paragraphs 53-57 of his affidavit that the ‘324 Patent was disclosed in the prior literature which allowed the person skilled in the art to work out the invention, namely the article by Weimann et al. For example, paragraph 56 reads:
¶56 A person skilled the art would understand from this extract that Weimann et al. meant to disclose that sildenafil causes pulmonary vasodilation in acute pulmonary hypertension, and more particularly, that sildenafil selectively lowers PVR without lowering SVR. In this regard, the disclosure in Weimann et al. is closely similar to the disclosure of the dog studies in the 324 Patent. In both the Weimann et al. sheep studies and the 324 Patent dog studies, pulmonary hypertension was induced in the test animals, sildenafil was administered, hemodynamics parameters were measured, the effect on PVR and SVR were determined and the conclusion was reached that sildenafil selectively lowers PVR as compared to SVR. Thus, Weimann discloses the use of sildenafil to treat pulmonary hypertension within the meaning of that term as it is used in the claims of the 324 Patent.
[54] Dr. Waxman repeats the same analysis with respect to the prior art in Atz et al., inter alia.
[55] With respect to obviousness, Dr. Waxman states that prior to the filing of the ‘324 Patent, the prior art had established the following knowledge:
1. PDE5 is the predominant phosphodiesterase in the pulmonary arteries;
2. PDE5 inhibitors as a class had been shown to be effective in treating pulmonary hypertension;
3. sildenafil was known as a safe and effective orally administrable medicine;
4. sildenafil was known to selectively reduce arterial pressure and had been recommended for use in treating pulmonary hypertension; and
5. sildenafil had been used clinically to successfully treat pulmonary hypertension.
Dr. Elliot’s evidence regarding the ‘324 Patent
[56] Dr. Elliot is a Professor of Medicine at the University of Utah School of Medicine and Chairman of the Department of Medicine at Intermountain Medical Center in Salt Lake City, Utah. He obtained his medical degree from the University of Maryland. His affidavit was sworn on February 17, 2009
[57] Dr. Elliot states that the term “pulmonary hypertension” is used to describe any condition which meets the accepted hemodynamic criteria established by the National Institutes of Health Registry on Primary Pulmonary Hypertension.
[58] Dr. Elliot states that many prior art documents proposed the utility of PDE5 inhibitors including sildenafil for treating pulmonary hypertension, and some reported studies in humans and animals.
[59] Dr. Elliot is of the view that the 1024 study is not capable of showing utility or sound prediction.
[60] Furthermore, the disclosure in the ‘324 Patent is said to be deficient in that it does not state the number of patients in the 1024 study upon which the ‘324 Patent relies, rendering the study scientifically meaningless.
ISSUES
[61] The issue raised by this prohibition application is whether the respondent Ratiopharm’s allegations that the '324 Patent is invalid are unjustified. Ratiopharm raised a number of issues in its NOA, which were argued before me:
1. Is the ‘324 Patent entitled to a claim date based on the November 2, 1999 patent filing in Great Britain GB 970?
2. Is the ‘324 Patent invalid for lack of sound prediction?
3. Is the ‘324 Patent invalid for obviousness in view of the prior art?
4. Is the ‘324 Patent invalid for lack of novelty or anticipation?
ANALYSIS
Burden of Proof
[62] In my VIAGARA decision I summarized at paragraph 36 the burden of proof that lies on the parties in an application for an order of prohibition under the NOC Regulations:
1. Novopharm has the evidentiary burden to present sufficient evidence to give its allegations of invalidity "an air of reality" (Novopharm's legal burden in this regard has been described in the jurisprudence as "a sufficient factual and legal basis for its allegations of invalidity with "sufficient" evidence on a balance of probabilities.") Then the burden shifts because the presumption of the patent's validity has been rebutted or overcome by Novopharm), i.e. that it can rebut the presumption of validity; and
2. Pfizer has the legal burden of proving on the balance of probabilities that Novopharm's allegations of invalidity are unjustified.
See also Abbott Laboratories v. Canada (Minister of Health), 2007 FCA 153, 361 N.R. 308, per Justice Sharlow at paragraphs 8-9; Pfizer v. Canada Inc. v. Canada (Minister of Health), 2007 FCA 209. 366 N.R. 347, per Justice Nadon at paragraphs 109-110; Pfizer v. Apotex, 2007 FC 971, 319 F.T.R. 48, per Justice Mosley at paragraphs 123-129; Pfizer Canada Inc. v. Apotex Inc., 2007 FC 26, 306 F.T.R. 254, per Justice O’Reilly at paragraph 12.
Patent Claim Construction
[63] The first step in a patent matter is to construe the patent claim. Claim construction is antecedent to consideration of both the validity and the infringement issues: Whirlpool Corp. v. Camco Inc. 2000 SCC 67, 9 C.P.R. (4th) 129 at para. 43. It applies to the whole of the patent, where necessary, and not only to the claims: Burton Parsons Chemicals, Inc. v. Hewlett-Packard (Canada) Ltd., [1976] 1 S.C.R. 555 at 563.
[64] Patent construction is to be done on the basis that the addressee is a person skilled in the art and the knowledge that person is expected to possess is to be considered. The hypothetical person who is skilled in the art possess the ordinary skills and knowledge of the particular art to which the invention relates, a mind willing to understand a specification, and is assumed to be someone who is going to try to achieve success and not one who is looking for difficulties or seeking failure: Free World Trust v. Electro Santé Inc. (2000), 2000 SCC 66, [2000] 2 S.C.R. 1024, 9 C.P.R. (4th) 168, per Justice Binnie at para. 44.
[65] Based on the affidavit evidence of both Pfizer’s and Ratiopharm’s experts, the Court finds that the person skilled in the art is a physician specializing in cardiology, pulmonology, or other internal medicine who treats patients suffering from pulmonary hypertension.
[66] In construing the claims for the purposes of considering the validity of the patent, the Court must look primarily to the claims. According to Hughes & Woodley on Patents (2nd ed. 2005), §26 at p. 311-12, the Court may resort to the specification only in limited circumstances:
In construing a patent, the claims are the starting point. The claims alone define the statutory monopoly and the patentee has a statutory duty to state, in the claims, what the invention is for which protection is sought. In construing the claims, recourse to the rest of the specification is: (1) permissible to assist in understanding the terms used in the claims; (2) unnecessary where the words are plain and unambiguous; and (3) improper to vary the scope or ambit of the claims. This does not mean that claims are never to be construed in light of the rest of the specification but it means that the resort is limited to assisting in comprehending the meaning in which words or expressions contained in the claims are used.
[67] The patentee is not able to re-write a claim in claims construction (Whirlpool, supra). It is also impermissible to use the process of claim construction to avoid the effects of prior art: Whirpool, supra, at para. 49.
[68] The '324 Patent relates to the use of sildenafil for the treatment of pulmonary hypertension.
[69] Pfizer relies on claims 1, 6 (as it depends on 1), 7 (as it depends on 6, as it depends on 1), 10, 15 (as it depends on 10) and 16 (as it depends on 15, as it depends on 10) of the '324 Patent which they state easily identifies the inventive concept of the patent. Those claims are set out below:
1. The use of an effective amount of sildenafil or a pharmaceutically acceptable salt, solvate or polymorph thereof, for the manufacture of a medicament for treating or preventing pulmonary hypertension.
[…]
6. The use according to any one of claims 1 to 5, wherein the medicament is suitable for oral administration.
7. The use according to claim 6, wherein sildenafil citrate is used.
[…]
10. The use of an effective amount of sildenafil or a pharmaceutically acceptable salt, solvate or polymorph thereof, for treating or preventing pulmonary hypertension.
[…]
15. The use according to any one of claims 10 to 14, wherein the effective amount is administered orally.
16. The use according to claim 15, wherein sildenafil citrate is used.
[…]
[70] The issues with respect to the construction of the ‘324 Patent claims are:
1. whether the patent is directed to the treatment of animals, as well humans?
2. whether the patent claims include co-administration of sildenafil with other drugs?
3. whether the term “pulmonary hypertension” is narrowly defined in the patent to include only the “pathological” variety of the disease.
[71] Drs. Elliot and Waxman, respectively state that the ordinary person skilled in the art would, in addition to the specialist physicians and pharmacologists, include veterinarians. There is no evidence that indicates that the ‘324 Patent relates to the use of sildenafil to treat pulmonary hypertension in animals. The fact that the ‘324 Patent makes reference to animal studies, and that pulmonary hypertension may occur in animals, (e.g. sheep in the form of Brisket’s disease) is not indicative of its intended use. The Court concludes that the ‘324 Patent relates to the treatment of humans, not animals. Accordingly, the ordinary person skilled in the art does not include a veterinarian.
[72] At paragraph 41 of his affidavit, Dr, Waxman states that the claims of the ‘324 Patent cover the use of sildenafil either alone or in combination with other compounds. (See also paragraph 38 of Dr. Elliot’s affidavit). He does so on the basis of line 20 at page 9 of the ‘324 Patent:
The compounds of the invention can also be administered together with prostacyclins (e.g. Epoprostenol), Oxygen, Calcium channel blockers (e.g. Nifedipine, Diltazem, Amlodipine), endothelin antagonists (ETa), iloprost, adenosine and/or nitric oxide.
[Emphasis added]
[73] Pfizer submits that the ‘324 Patent simply states it is would be safe to administer sildenafil with other compounds. According to Pfizer, the claim is directed to “taking enough sildenafil to treat pulmonary hypertension”, as opposed to taking sildenafil in combination with another substance to effectively treat pulmonary hypertension. Pfizer emphasizes the phrase “effective amount”, which it submits indicates the use of a smaller amount of sildenafil for treating pulmonary hypertension, than the amount needed to treat ED alone, and not in combination with other drugs. There is no basis for accepting Pfizer’s proposed construction.
[74] Dr. Butrous acknowledged that patients in the 1024 study were treated for pulmonary hypertension with calcium channel blockers and NO among other drugs. Some of the prior art in the late 1990’s discussed the use of sildenafil in combination with other drugs to lower PVR. The science at the time appears to not have favoured the use of sildenafil to treat pulmonary hypertension in isolation.
[75] Furthermore, this Court has held in Abbot Laborarories Ltd. v. Canada (Minister of Health), 2006 FC 1411, 304 F.T.R. 104, per Justice Von Finckenstein at paragraph 26, affirmed on this point in 2007 FCA 251, 367 N.R. 120 at paragraph 16, that in construing patent claims the Court cannot import implicit or explicit limitations with respect to drug mixtures, unless the claims specifically direct such limitation:
¶26 Thus, even if there was a limitation implicit or explicit in the disclosure, it could not be imported into the claims. Drugs often are not administered in a pure state but mixed with an excipient or other drugs and the use of such drugs would be highly restricted if the mention of a use of a drug would be read as implying it has to be used alone. Unless the use claimed specifically employs such words as "alone" or "not in conjunction with other compounds" it would be improper to read such a limitation into the claim…
The ‘324 Patent claims do not explicitly limit the application of sildenafil in isolation. There is no basis for importing such a limitation either in the patent’s language or the scientific view of the day.
[76] Pfizer submits that the phrase “pulmonary hypertension”, as it is stated in Claim 1 of the Patent, should be qualified by the phrase “pathological”, as it appears at page 1 of ‘324 Patent’s specification:
Pulmonary hypertension is a pathological condition in which the pulmonary arterial pressure rises above normal levels and may cause sequelae of hemodynamic changes that become life threatening. Symptoms of pulmonary hypertension include shortness of breath with minimal exertion, fatigue, dizzy spells and fainting...
In the same page, the specification goes on to state:
Since pulmonary hypertension is caused typically by constriction of the pulmonary blood vessels, vascular resistance is the favoured indicator of the disease.
[77] In my view the words in Claim 1 are clear and unambiguous. Limiting the scope of the ‘324 Patent in the manner Pfizer submits is inconsistent with its wide use as a vasodilator in a variety of circumstances and sub-conditions found in patients of pulmonary hypertension. The patent states at page 9 that:
…Compounds of the invention can also be used to treat children who have pulmonary hypertension post operatively or due to respiratory distress syndrome or neonatal hypoxia.
[78] The Court will now construe the relevant patent claims. Taking into consideration the relevant patent claims and with the aid of the expert evidence, the essential elements of the claims can be described as follows:
The use of sildenafil, sildenafil citrate, or a salt of sildenafil, in the form of an oral medicine, for the treatment of pulmonary hypertension in humans. The dosage can vary, and sildenafil can be administered alone, or in combination with other medicine. The patent does not limit the type of pulmonary hypertension for which sildenafil is an effective treatment.
Issue No. 1: Is the ‘324 Patent entitled to a priority date claim based on GB 970?
[79] Pfizer submits that the ‘324 Patent is entitled to an earlier priority claim date because of its prior application for a United Kingdom patent, GB 9925970.7 (“GB 970”), filed on November 2, 1999. Pfizer submits that GB 970 discloses the same subject matter as claim 10 in the ‘324 Patent, by restating in almost identical language that sildenafil can be effectively used for treating pulmonary hypertension.
[80] Ratiopharm submits that GB 970 does not disclose the same invention as the ‘324 Patent because GB 970 only recites the unproven hypothesis that due to its known mechanism of action as a powerful and selective PDE5 inhibitor, sildenafil could be used to treat pulmonary hypertension.
The Law
[81] Paragraph 28.1(1)(a)(ii) of the Act, enacted in 1993, allows a Canadian patent to claim an earlier date (the “priority date”) for protection if the person or their representative previously applied for patent protection in a foreign jurisdiction that discloses the “subject matter” def