Sanofi-Aventis Canada Inc. v. Hospira Healthcare Corporation

Sanofi-Aventis Canada Inc. v. Hospira Healthcare Corporation
Court (s) Database
Federal Court Decisions
Date
2009-10-22
Neutral citation
2009 FC 1077
File numbers
T-2080-07
Notes
Reported Decision
Decision Content
Federal Court
Cour fédérale
Date: 20091022
Docket: T-2080-07
Citation: 2009 FC 1077
BETWEEN:
SANOFI-AVENTIS CANADA INC.
Applicant
and
HOSPIRA HEALTHCARE CORPORATION and
THE MINISTER OF HEALTH
Respondents
REASONS FOR JUDGMENT
ZINN J.
[1] This is an application brought by Sanofi-Aventis Canada Inc. (Sanofi Canada) under section 6 of the Patented Medicines (Notice of Compliance) Regulations, SOR/93-133, as amended (NOC Regulations) for an order prohibiting the Minister of Health from issuing a Notice of Compliance (NOC) to Hospira Healthcare Corporation (Hospira) until after the expiration of Canadian Patent No. 2,102,778 (the '778 patent).
[2] In its Notice of Allegation (NOA) dated October 15, 2007, Hospira alleged non-infringement and invalidity against the '778 patent, and two other patents marketed by Sanofi Canada: Canadian Patent No. 2,102,777 (the '777 patent) and Canadian Patent No. 2,150,576 (the '576 patent). Hospira accepted that its notice of compliance would not issue until after the expiration of a fourth patent marketed by Sanofi Canada, Canadian Patent No. 1,278,304, which expired December 27, 2007. The alleged non-infringement and invalidity of the '777 patent and '576 patent are not at issue between the parties since Sanofi Canada subsequently limited its Notice of Application to the ‘778 patent.
[3] On November 28, 2007, the patentee filed a notice of disclaimer disclaiming parts of claims 1 to 8 of the ‘778 patent. On the next day Sanofi Canada commenced this proceeding. Claim 8, as disclaimed, is the only claim of the ‘778 patent at issue in these proceedings. Where relevant, I will refer to the patent and claims 1 and 8 after the disclaimer as the Disclaimed ‘778 patent, Disclaimed Claim 1 and Disclaimed Claim 8.
[4] For the reasons that follow the application is dismissed.
THE PARTIES
[5] The Applicant, Sanofi Canada, distributes and sells pharmaceutical products. One such product, the drug at issue, is docetaxel which it markets in Canada under the brand name Taxotere. Sanofi Canada is known as the “first person” under the NOC Regulations.
[6] The Respondent Hospira is a generic drug company, known as the “second person” under the NOC Regulations. Hospira has filed with the Minister a new drug submission (NDS) for docetaxel for injection comprising docetaxel, in a strength of 10 mg/mL, in 2 mL, 8 mL and 16 mL vials (the Hospira Product). Under the NOC Regulations Hospira was obliged to provide an NOA to Sanofi Canada, which had the patents mentioned above listed on the patent register in respect of docetaxel.
[7] The Minister, following receipt of a drug submission and after following the required procedures has the responsibility to issue an NOC to permit the sale and distribution of certain drugs in Canada. The Minister was not represented in these proceedings although she was served with the necessary documents.
THE DRUG
[8] Docetaxel is a drug used to treat various forms of cancer. Sanofi Canada supplies it in a concentrated solution under the trade name Taxotere, which then must be diluted to form an infusion prior to its injection into the body. Docetaxel is synthetically derived from paclitaxel. Both docetaxel and paclitaxel are members of the taxane class of chemotherapy drugs derived from the European yew tree (Taxus baccata).
[9] In an ideal world, medical researchers would discover compounds that are non-toxic, highly soluble and physically stable in aqueous solutions. If drugs are toxic then their harmful side effects may outweigh their pharmacological benefits. If drugs have low solubility in water (of which humans are composed) then other solvents must be used to dissolve the compounds, and various techniques must be employed to ensure continued solubility when the compound is prepared in a water-based infusion for the administration into the human body. Quite frequently these solvents are themselves toxic. Further, low solubility can result in only solutions with a small amount of active drug being able to be made, which can diminish their effectiveness. If drugs are not physically stable, then when they are introduced into the human body, they can quickly precipitate out of their solution (i.e. form solid clumps) and either not be transferred to the place in the body where they need to work, or have their chemical structure changed in such a manner as to render them less than useful or useless at treating the ailment for which they were designed. The world is not ideal. Pharmaceutical companies must address all these issues in bringing their novel compounds from the scientist's bench to the pharmacist’s shelf.
[10] While taxanes are known to have significant affects on malignant tumours, they are difficult to formulate because of their poor water solubility. Docetaxel and paclitaxel are no different. This poses problems as described above. The invention in question protected by the ‘778 patent does not relate to the specific structure of either docetaxel or paclitaxel. Rather, the invention relates to how these drugs can be formulated with other ingredients so as to permit their administration into the human body in an effective form.
[11] Prior to Sanofi Canada’s invention, the prior art taught the following formulation: a stock solution was prepared by mixing docetaxel with equal parts of ethanol and Cremophor® EL (Cremophor). This solution was then mixed with an infusion fluid such as saline or dextrose. Ethanol is a common solvent used in drug formulation. Cremophor is a surfactant. Surfactants, in effect, cling to the surface of other molecules thereby altering their chemical behaviour. One important way that surfactants can alter a molecule's behaviour is by increasing solubility without altering other attributes. It was precisely this modification, increased solubility, that the surfactant Cremophor brought to the solution that made it an essential component.
[12] The problems with this formulation were two-fold. Firstly, both ethanol and Cremophor have side effects. Ethanol results in intoxication. Cremophor can result in anaphylactic shock. Secondly, in order to achieve a formulation that is both physically and chemically stable it was necessary to limit the docetaxel concentration to 0.03-0.6 mg/mL. To be clinically useful, docetaxel concentrations ranging from 0.3-1.0 mg/mL are needed. As a result, the prior art formulation would require large volumes of solution being injected into a patient to administer the desired quantity of the active ingredient, thus increasing the likelihood of the patient becoming intoxicated from the ethanol or experiencing anaphylactic shock caused by the Cremophor.
[13] The Sanofi Canada invention lessened these problems. Sanofi Canada discovered that Cremophor could be replaced with polysorbate 80, an alternative surfactant. With this alteration, Sanofi Canada removed Cremophor from the stock solution, the source of possible anaphylactic shock. Further, it found that with this modification the previously required amount of ethanol could also be reduced and that the concentration of the active ingredient docetaxel could be increased. The Sanofi Canada stock product consists of docetaxel as the active ingredient, mixed with ethanol and polysorbate 80.
[14] The Hospira stock solution consists of docetaxel as the active ingredient, mixed with ethanol, polysorbate 80 and two other ingredients: Ingredient A and Ingredient B. It is unknown or unclear what value Ingredient A adds to the formulation. However, much but not all of the polysorbate 80 is replaced with Ingredient B, another surfactant, and this permits the concentration of docetaxel to be increased. The Hospira Product permits the stock solution to have docetaxel in a strength of 10 mg/mL whereas the Sanofi Canada product has a strength of 1 mg/mL. Like the Sanofi Canada product, the Hospira Product must be added to an infusion solution prior to injection into the human body.
THE PATENT
[15] As noted above, the only patent remaining at issue is the ‘778 patent. The ‘778 patent entitled Novel Compositions Based on Taxane Class Derivatives, was filed in Canada on July 3, 1992, and issued on April 20, 2004. It claims priority to French Patent Application 91 08527 dated July 8, 1991. The ‘778 patent was filed in the French language. The parties relied on the English language translation of the patent that was filed as part of the record in this proceeding.
[16] The relevant portion of the description of the ‘778 patent is as follows:
The present invention concerns a novel pharmaceutical form made from a therapeutic agent with antitumor and antileukemic activity. More specifically, it concerns a novel injectable form containing products from the taxane family, such as, notably, taxol or one of its analogues or derivatives with the following general formula:
[17] Claims 1, 2 and 8 of the ‘778 patent read as follows:
1. Compositions made from at least one product in the taxane family or one of its analogues or derivatives in a solution of ethanol and polysorbate.
2. Composition made from a formula (I) derivative:
in which R represents a hydrogen atom or an acetyl radical, the symbol R1 represents a tert-butoxycarbonylamino or benzolotlamino radical in solution in a mixture of ethanol and polysorbate.
8. Infusion that contains approximately 1 mg/mL or less of formula (I) compounds as defined in claim 2 and that contains less than 35 ml/L of ethanol and less than 35 ml/L of polysorbate.
[18] All of the claims of the ‘778 patent were disclaimed, except that claims 1 and 8 were disclaimed to the following:
1. A composition under the form of a solution designed to be formulated for infusion, containing between 6 to 15 mg/mL of a derivative with formula (I)
in which R represents a hydrogen atom and R1 is a tertiobutoxycarbonylamino radical, in a mixture of ethanol and polysorbate, the ethanol concentration being greater than 5%.
8. An infusion including more than 0.1 mg/mL and less than 1 mg/mL of a compound with formula (I) as defined here above, and which includes more than 5 ml/L and less than 35 ml/L of ethanol and more than 5 ml/L and less than 35 ml/L of polysorbate.
[19] The disclaimer with respect to claim 1 meant that the patentee was claiming only for docetaxel and not paclitaxel or any other taxane as the active ingredient. The disclaimer with respect to claim 8 narrowed the range of docetaxel as well as the ranges of ethanol and polysorbate.
THE NOA AND DISCLAIMER
[20] The NOA, as directed to the ‘778 patent (prior to the disclaimer), alleges (1) no claim for the medicinal ingredient, no claim for the formulation, no claim for the dosage form and no claim for the use of the medicinal ingredient would be infringed or induced to be infringed by the making, constructing, using or selling by Hospira of the Hospira Product, in accordance with the NDS; (2) that the claims of the ‘778 patent are invalid for anticipation, obviousness, claims broader than the invention made and/or disclosed (contrary to section 27(4) of the Patent Act), material misstatement (contrary to section 27(3) of the Patent Act), lack of utility, double patenting, the Gillette Defence, and ineligibility for listing on the Patent Register.
[21] After the NOA was served on the applicant and prior to it filing this application, Sanofi Canada disclaimed the claims of the ‘778 patent, as described above. The application proceeded until just prior to hearing on the claims of the ‘778 patent as disclaimed. Hospira reduced its attack on Disclaimed Claim 8 to the following allegations:
a. The Hospira Product does not infringe the Disclaimed ‘778 patent; and
b. Disclaimed Claim 8 is invalid on the following grounds:
i. claims broader than the invention made or disclosed;
ii. anticipation;
iii. obviousness;
iv. avoidable ambiguity;
v. sufficiency; and
vi. method of medical treatment.
[22] With respect to anticipation Hospira submitted that Disclaimed Claim 8 was anticipated by the following prior art references: (1) F. Guéritte-Voegelein et al., “Relationship between the Structure of Taxol Analogues and Their Antimitotic Activity”, Journal of Medicinal Chemistry, Vol. 34, No. 3, March 1991, pp. 992-998 (the GV Article), (2) B.D. Tarr et al., “A New Parenteral Vehicle for the Administration of Some Poorly Water Soluble Anti-Cancer Drugs”, Journal of Parenteral Science, 41(1): 31-33 (January-February 1987) (the Tarr Article); and (3) US Patent No. 4,206,221, Miller (the ‘221 patent).
[23] In its Memorandum of Fact and Law filed June 8, 2009, Hospira raised as an issue whether it was required to respond to the ‘778 patent as it read at the date the NOA was served or as it read after having been disclaimed. It took the position that as the NOA was served prior to the disclaimer, this Court’s recent jurisprudence was that the Court must consider only the patent as it read on the date the NOA was served and not as it read after the disclaimer was filed. Hospira also made submissions relating to the validity of the disclaimer, avoidable ambiguity, and method of medical treatment. Hospira submits that the disclaimer is not valid for two reasons. First, it submits that Sanofi Canada has failed to discharge its burden of establishing that the disclaimer meets the requirements of Section 48(6) of the Patent Act. Secondly, it submits that it is invalid as it improperly broadens the scope of the claim rather than narrowing it. In this respect, it submits that Disclaimed Claim 8 changed the word “contains” to “includes” in an “attempt to recast the claim to broaden the scope of the claims to cover additional ingredients as is contained in Hospira’s formulation.”
[24] Sanofi Canada responded with a motion to strike the paragraphs from Hospira’s Memorandum of Fact and Law that raised these issues and, in the alternative, sought leave to file reply evidence in response to what it said were new allegations. Hospira countered with its own motion seeking to strike the entirety of Sanofi Canada’s application on the basis that only the patent as it read at the date the NOA was served was relevant and, as Sanofi Canada had failed to lead any evidence on infringement and validity of the ‘778 patent as construed according to their original claims, its application was an abuse of process and ought to be dismissed.
[25] Prothonotary Tabib dismissed both motions. In her Amended Order dated September 8, 2009, Prothonotary Tabib held that Hospira ought not to have brought its motion so late and that it was not plain and obvious that the application could not succeed. Prothonotary Tabib also held that Sanofi Canada would be allowed to file additional evidence on the validity of the disclaimer and on the issue raised as to whether Hospira was estopped from challenging the disclaimer at this point. The Court subsequently permitted Hospira to file sur-reply evidence.
THE EVIDENCE
[26] Sanofi Canada submitted affidavits in support of its application from Franca Mancino, Dr. Panayiotis P. Constantinides, and Dr. Jean-Christophe Leroux. Hospira submitted affidavits from Dr. David Attwood and Dr. Joseph Bogardus.
[27] After the issues relating to the disclaimer were identified by Hospira and with leave of the Court, Sanofi Canada submitted affidavits from Gerald V. Dahling, Michael Alt, Thierry Orlhac and Robert Kajubi in reply to these new arguments of Hospira.
The Applicant’s Evidence on the Merits of the Application
[28] Franca Mancino is the Senior Director, Regulatory Affairs, Pharmacovigilance and Quality and Compliance at Sanofi Canada. She swore an affidavit on May 22, 2008 describing the concentrated formulations of docetaxel for which Sanofi Canada had received NOCs. Ms. Mancino provided a copy of the Product Monograph of Taxotere that explained how these concentrated formulations are to be diluted into a perfusion for administration to the patient. She also swore that the ‘778 patent was listed on the Patent Register, and listed on the Form IV Patent List as part of the original new drug submission for the various NOCs.
[29] Dr. Panayiotis P. Constantinides is the founder and principal of a pharmaceutical consulting company. He obtained his Ph.D. in Biochemistry at Brown University where his thesis work related to the physical chemistry of surfactant micelles. Polysorbate 80, used in the invention of Sanofi Canada, is a surfactant that forms micelles with docetaxel, thereby facilitating the latter’s solubility in aqueous solutions. Dr. Constantinides did post-doctoral work at Yale University, and has experience in the pharmaceutical sector on drug solubilisation issues, including the use of taxanes.
[30] Dr. Constantinides swore an affidavit on May 27, 2008 commenting on Hospira’s allegations of invalidity relating to the ‘778 patent. Prior to making his comments, counsel for Sanofi Canada provided him with Hospira’s NOA, the references referred to in the NOA, the ‘778 patent, and the disclaimer dated November 28, 2007.
[31] Dr. Constantinides describes the invention as disclosed by the ‘778 patent. He asserts that the person skilled in the art (PSIA) would have at least a Bachelor of Science degree in the life sciences, along with relevant scientific or non-scientific work experience in developing intravenous formulations of poorly soluble drugs. Dr. Constantinides construes the Disclaimed Claim 8 of the ‘778 patent to include the following essential elements:
a. an infusion of docetaxel of more than 0.1 mg/mL and less than 1 mg/mL;
b. more than 5 ml/L and less than 35 ml/L of ethanol; and
c. more than 5 ml/L and less than 35 ml/L of polysorbate.
[32] Dr. Constantinides’ view is that a PSIA would read the Disclaimed Claim 8 to include other components beyond the essential elements listed.
[33] Dr. Constantinides concludes that none of the prior art references would inevitably teach all the components of Disclaimed Claim 8 as construed. He says that the GV Article failed to anticipate because even though it disclosed docetaxel dissolved in ethanol and polysorbate, it did not relate to an infusion, and provided no information on the relative concentrations of the solvent vehicle.
[34] Dr. Constantinides concludes that the Tarr Article did not anticipate because it referred to paclitaxel and not docetaxel as required by the Disclaimed Claim 8. Additionally, he observes that the paclitaxel infusion disclosed was not stable and therefore not useful for administration intravenously.
[35] He says that the ‘221 patent did not anticipate because it implied a bolus injection, as opposed to an intravenous injection, and did not disclose the specific composition of the injectate.
[36] Dr. Constantinides states that it is not possible to predict a drug’s solubility in a given solvent mixture, and that solubility has to be determined through experimentation. Dr. Constantinides says that minor variations to a drug’s structure could alter its solubility, preventing definitive conclusions from experimentation on one drug to be drawn for another. He describes the various solvent vehicles available to a PSIA in the late 1980s and early 1990s, as well as the other methods available for solubilising poorly soluble drugs and concludes that it would not be obvious to a PSIA which method would be best to solubilise docetaxel in a manner that excluded Cremophor and that it would not be obvious to take what worked with paclitaxel and apply it to docetaxel.
[37] Dr. Jean-Christophe Leroux is a Professor in the Faculty of Pharmacy at the University of Montréal. He completed his Ph.D. in pharmaceutical sciences at the University of Geneva. Prior to becoming a member of the faculty at the University of Montréal, Dr. Leroux was a postdoctoral fellow at the University of Geneva and the University of California, San Francisco. Dr. Leroux’s principal areas of research are in surface active molecules and methods to dissolve hydrophobic drugs, including paclitaxel and docetaxel. He has published a number of peer-reviewed articles on micelles and the related solubilisation of hydrophobic drugs.
[38] Dr. Leroux swore an affidavit on May 26, 2008 in which he comments on whether Hospira’s Product fell within the range of what was set out in the Disclaimed Claim 8 of the ‘778 patent. He also comments on Hospira’s allegations of invalidity relating to the ‘778 patent. In making these comments, Dr. Leroux referred to the NOA of Hospira, the references referred to in the NOA, Hospira’s formulation information, the ‘778 patent, and the disclaimer filed on November 28, 2007. He was asked to focus only on Disclaimed Claim 8 of the ‘778 patent.
[39] Dr. Leroux describes solubility studies that his research group has conducted on paclitaxel and docetaxel. These studies show that despite structural similarities, the two molecules are characterized by different physicochemical properties. According to Dr. Leroux, these differences would have been apparent to the PSIA in the late 1980s or early 1990s.
[40] Dr. Leroux also describes the challenge this insolubility causes in preparing an intravenous infusion of docetaxel, and the inventive aspect of Sanofi Canada’s formulation. He states that the prior art did not sufficiently disclose the invention. Dr. Leroux states that even today formulating such drugs proceeds on the basis of trial and error and that this is particularly so because it is not always possible to apply experience in formulating one drug to the formulation process of a second drug.
[41] After reviewing the legal principles of claim construction provided by counsel for Sanofi Canada, Dr. Leroux construed the Disclaimed Claim 8 of the ‘778 patent to include the following essential elements: an infusion solution containing the following: (i) 0.1 to 1 mg/mL of docetaxel, (ii) 5 to 35 ml/L of ethanol, and (iii) 5 to 35 ml/L of polysorbate. Dr. Leroux states that the word “includes” in the context of the Disclaimed Claim 8 would be read by the PSIA to be non-exhaustive – it would not mean “includes only”.
[42] Dr. Leroux calculated Hospira’s Product to include: (i) 0.3 to 0.74 mg/mL of docetaxel, (ii) 6.9 to 17.02 mL/L of ethanol, and (iii) 7.22 to 17.81 mL/L of polysorbate 80. These ranges fall within the ranges stated in Disclaimed Claim 8 of the ‘778 patent.
[43] Dr. Leroux reviewed the GV Article, concluding that it did not relate to an infusion solution, did not focus on the stability needed for intravenous injection, and did not include the percentage of ethanol and polysorbate present in the final solution. He also reviewed the Tarr Article, concluding that it did not refer to docetaxel, but even to the extent that it discussed paclitaxel, that it did not relate to an infusion. Dr. Leroux also reviewed the ‘221 patent, concluding that docetaxel was not referred to, and that there was no information on the percentage of ethanol and polysorbate in the solution.
[44] Dr. Leroux describes the various options available in the early 1990s for formulating highly insoluble molecules, such as cosolvents, low molecular weight surfactants, polymeric surfactants, emulsions, complexing agents, and mixtures of excipients when applicable. Dr. Leroux concludes that the prior art would not lead a PSIA directly and without difficulty to the invention taught by the ‘778 patent because each piece of prior art either did not refer to an infusion and/or did not refer to docetaxel. He notes that one piece of prior art did refer to a docetaxel infusion, but this piece contained emulphor, not polysorbate. Given these various options, and prior art, Dr. Leroux expresses the view that a PSIA would not be led directly and without difficulty to the ethanol and polysorbate combination of Sanofi Canada’s ‘778 patent.
[45] Dr. Leroux states that a PSIA would read the Disclaimed Claim 8 of the ‘778 patent as a non-exhaustive list, including the essential elements of docetaxel, ethanol and polysorbate, but not limited to these elements. Dr. Leroux also says that the Disclaimed ‘778 patent is sufficiently clear to allow the PSIA to work the invention.
The Respondent’s Evidence on the Merits of the Application
[46] Dr. David Attwood was a Professor in the School of Pharmacy and Pharmaceutical Sciences at the University of Manchester prior to his retirement in 2008. He is now Professor Emeritus at the University of Manchester. He obtained his Ph.D. from the School of Pharmacy at the University of London. He has taught courses and supervised graduate research on the formulation of pharmaceutical systems. Dr. Attwood has consulted on formulation issues, particularly involving surfactants, with a number of pharmaceutical companies, and he has also co-authored textbooks on surfactant systems.
[47] Dr. Attwood swore an affidavit on September 12, 2008 commenting on the relevant PSIA, the construction of the Disclaimed ‘778 patent, and Hospira’s allegations of non-infringement and invalidity. Prior to making these comments, Dr. Attwood was provided with copies of the ‘778 patent, the November 28, 2007 disclaimer, the prior art referred to in Hospira’s NOA, the Mancino affidavit, the Leroux affidavit, the Constantinides affidavit, Hospira’s formulation and product monograph, and Hospira’s NOA.
[48] Dr. Attwood characterizes the PSIA as someone with at least a Bachelor of Science in a relevant discipline, two years of post-graduate experience in pharmaceutical formulations or several years in formulations generally, and experience in the development of intravenous formulations of poorly water soluble drugs. The PSIA would have knowledge of the use of surfactants to facilitate solubilisation of drugs in aqueous solutions through the formation of micelles.
[49] Dr. Attwood states that the Disclaimed ‘778 patent relates to pharmaceutical injectable formulations of four members of the taxane class of drugs. In construing the Disclaimed ‘778 patent, Dr. Attwood says that the essential elements are an infusion solution containing a taxane, polysorbate and ethanol. Dr. Attwood contends that the ranges of docetaxel, ethanol and polysorbate would not have been essential from the perspective of the PSIA in January 1993. Dr. Attwood says that there is no rationale for the range of concentrations listed in the Disclaimed Claim 8 with respect to docetaxel, ethanol, or polysorbate, and that they appear to be arbitrary in the context of the inventive replacement of Cremophor with polysorbate.
[50] After reviewing and describing the invention disclosed by the ‘778 patent, Dr. Attwood says that the use of the word “contains” in the original claim 8 would be read by a PSIA to mean an exhaustive list. Dr. Attwood also says that the use of the word “including” in the Disclaimed Claim 8 would also be read to mean an exhaustive list, because ethanol was listed as the only solvent used, polysorbate was listed as the only surfactant used, the examples included no other ingredients, and a PSIA would have known that additional surfactants, stabilizers and/or preservatives could affect the formation and properties of micelles. According to Dr. Attwood, the PSIA would have expected the inventors to list any additional ingredients in the formulation, particularly given that the inventive step was the removal of Cremophor.
[51] Dr. Attwood determined that the GV Article did disclose the formulation of Disclaimed Claim 8. The GV Article teaches a solvent vehicle for docetaxel of 1:1 ethanol to polysorbate that is identical to the ‘778 patent. According to Dr. Attwood, a PSIA would have understood that this formulation would have to be diluted into an infusion prior to administration in humans. Dr. Attwood states that a stock solution containing 6 mg/mL of paclitaxel would have been known to the PSIA, and that the ideal concentration for an infusion would also have been known. From this knowledge, a PSIA could make the invention described in the Disclaimed Claim 8 of the ‘778 patent. Dr. Attwood concludes that only routine solubility testing would be required to take this information and prepare a stable infusion within the specifications of the ‘778 patent.
[52] Dr. Attwood also concludes that the Tarr Article anticipates the Disclaimed Claim 8 of the ‘778 patent. According to Dr. Attwood, the Tarr Article disclosed the solubilisation of paclitaxel in a mixture of polysorbate and ethanol, along with other ingredients, to form a stock solution of 5 mg/mL, in preparation for the formulation of an infusion, with the final formulation having polysorbate and ethanol concentrations within the range of the Disclaimed Claim 8.
[53] Dr. Attwood maintains that the ‘221 patent disclosed an infusion containing paclitaxel, polysorbate and alcohol. According to Dr. Attwood, a PSIA would know that alcohol in this context means ethanol, and that the polysorbate would be included to function as a surfactant in the formation of micelles. Dr. Attwood noted that the ‘221 patent did not disclose the concentrations of ethanol and polysorbate in the final infusion, but that this was not important because the concentrations in Disclaimed Claim 8 were not essential to the invention.
[54] Dr. Attwood is of the view that the PSIA desiring to formulate docetaxel for an infusion, would have been aware of the available stock solutions of paclitaxel, would have been aware of the problems with Cremophor, and would have been immediately led to polysorbate as a replacement. The PSIA would have started with a 6 mg/mL stock solution of docetaxel, and would only have had to conduct minor solubilisation studies to make a final formulation according to the clinician’s desired final concentration. While other solvent vehicles were available, Dr. Attwood says that the PSIA would have chosen polysorbate and ethanol as the first and most practical choice.
[55] Dr. Attwood comments on the allegations of over breadth. He repeats his view that the Disclaimed Claim 8 was limited to the delineated ingredients, and argues that otherwise, the claim would be broader than the invention described. Alternatively, if Claim 8 did include other ingredients, Dr. Attwood argues that it insufficiently explained how those ingredients were to be incorporated in the formulation.
[56] Dr. Attwood contrasts his conclusions on these issues to those of Dr. Leroux and Dr. Constantinides, stating where he agreed and disagreed with their analysis; there was very little agreement.
[57] Dr. Bogardus is a consultant for the pharmaceutical industry. He obtained his Ph.D. in pharmaceutical chemistry from the University of Kansas. His thesis focused on solubilising certain drugs. He was a Professor in the College of Pharmacy at the University of Kentucky. Dr. Bogardus also worked for a number of years at Bristol-Myers Squibb where he was responsible for the development of paclitaxel as well as other poorly water soluble anti-cancer drugs. He has authored a number of articles on this subject.
[58] Dr. Bogardus swore an affidavit on September 17, 2008 commenting on the PSIA, the essential elements of Disclaimed Claim 8 of the ‘778 patent, whether Disclaimed Claim 8 was exhaustive, and the allegations of non-infringement and invalidity. Dr. Bogardus was referred to the same materials as Dr. Attwood.
[59] Dr. Bogardus is of the view that the PSIA would have at least a Bachelor of Science in a relevant scientific discipline, with experience in parenteral dosage forms, and some experience in formulations of poorly water soluble drugs. The PSIA would also be expected to have access to relevant texts on solubilisation, as well as access to related scientific professionals.
[60] Dr. Bogardus says that the essential elements of Disclaimed Claim 8 are:
a. an infusion of;
b. a taxane;
c. polysorbate; and
d. ethanol.
[61] After reviewing the Disclaimed ‘778 patent, Dr. Bogardus concludes that the ranges within the Disclaimed Claim 8 appear to be arbitrary, and that there is nothing inventive in the ranges. Dr. Bogardus also says that the Disclaimed Claim 8 was limited to the items listed, and does not include additional ingredients.
[62] Dr. Bogardus reviewed the formulation of Hospira, and determined that the inclusion of Ingredient B in that formulation would have a material affect, and in particular, on the formation of micelles and stability.
[63] Dr. Bogardus states that the PSIA would not normally read the journal containing the GV Article, but that in the early 1990s, a search of the literature would have identified the GV Article, as well as the Tarr Article and the ‘221 patent. Dr. Bogardus argues that regardless, the PSIA would have other professionals who would have informed the PSIA on the information contained in the GV Article. Dr. Bogardus concluded that the GV Article disclosed all the elements of the Disclaimed Claim 8, namely docetaxel, in a 1:1 polysorbate to ethanol infusion. It would have been logical to the PSIA to start with docetaxel stock solution concentrations in line with the already known stock concentrations of paclitaxel, i.e. 6 mg/mL. From this information, the PSIA could make the invention as described in Disclaimed Claim 8.
[64] Dr. Bogardus determines that the Tarr Article disclosed an infusion with paclitaxel, ethanol and polysorbate. Given Dr. Bogardus’s conclusion that docetaxel was not essential to Disclaimed Claim 8, he determined that this information disclosed the invention. Dr. Bogardus also commented that the PSIA would have been aware that the problems of crystallization described in the Tarr Article would be problematic clinically.
[65] Dr. Bogardus concludes that the ‘221 patent disclosed the infusion characterized by the Disclaimed Claim 8, and that even though the formulation was prepared for administration to mice, the PSIA would be able to apply the same formulating principles to humans.
[66] Dr. Bogardus describes the steps that a PSIA would take in approaching the formulation of a docetaxel infusion to be as follows:
i.consider the formulation of paclitaxel as a starting point due to structural similarities of the two molecules, as well as the problems with Cremophor;
ii.consider polysorbate 80 as an alternative to Cremophor given its similar non-ionic characteristics and the available prior art; and
iii.start with a stock solution of 6 mg/mL given the knowledge that such a stock solution worked with paclitaxel.
[67] Dr. Bogardus says that these steps, combined with clinical instructions on final concentration requirements, and routine stability testing, would lead directly and without difficulty to the invention.
[68] Dr. Bogardus argues that if the Disclaimed Claim 8 was construed to include additional ingredients then the invention is broader than what is described, and does not adequately instruct how to make it. Dr. Bogardus also argues that if the concentration ranges of the various components are essential then the invention does not describe how to make it.
[69] Dr. Bogardus compared and contrasted his conclusions with those of Dr. Leroux and Dr. Constantinides; there was substantial disagreement on the main issues.
Applicant’s Evidence on the Disclaimer
[70] Gerald V. Dahling in an affidavit sworn on September 3, 2009 states that prior to his retirement on June 1, 2008 he was Vice President Group Patent Counsel for the Sanofi Canada group. He was involved in recommending and making the decision to file the disclaimer of the ‘778 patent. He provides the following as to the reason for filing the disclaimer:
On October 15, 2007, Hospira sent a Notice of Allegation relating to, among others, the ‘778 Patent. In the Notice of Allegation, Hospira alleged that the ‘778 Patent was invalid for Double Patenting in light of Canadian Patent 2,102,777 (the “ ‘777 Patent”). This was the first such allegation of Double Patenting relating to the ‘778 Patent in view of the ‘777 Patent that anyone in the sanofi-aventis organization was aware of. Upon review of the issue, we recognize that there was potential overlap in the scope of the claims of these two patents and a decision was made to narrow the scope of Claim 8 of the ‘778 Patent to limit the active substance to docetaxel (thereby removing paclitaxel from the scope of the claim) and to narrow the range of docetaxel as well as the ranges of ethanol and polysorbate.
[71] Thierry Orlhac swore an affidavit on September 2, 2009. He is a partner at Leger Robic Richard LLP and a registered Patent Agent in both Canada and the United States. He filed the disclaimer. He states that:
As a result of Hospira’s allegation, and to ensure that the Canadian patents were being handled in accordance with then-applicable Canadian law, I was asked to file a disclaimer to remove any possible overlap between the ‘777 Patent and the ‘778 Patent. I was also asked to remove paclitaxel from the scope of the claims to address any potential prior art concerns with that compound and to limit the claims to docetaxel.
He further attests that the word “contient” (“contains”) in the original patent and the word “comprenant” (“including”) in the disclaimer, “in Canadian prosecution … are equivalent and that the disclaimer does not therefore broaden the scope of the original claim.”
[72] Dr. Michael Alt, a consultant with partner status at Bird & Bird LLP, Germany, swore an affidavit on August 31, 2009. He was asked to provide an opinion on whether the overlapping subject matter, to the extent that there is any, in the Patent Cooperation Treaty (PCT) applications, would be of concern under the PCT and European patent convention and patent practice at the time they were filed and prosecuted in the International phase. He explains that he is “not aware that the PCT provides any legal basis for raising a double patenting objection ... [and he has] never seen a double protection objection when prosecuting PCT phase applications.”
[73] Lastly, Robert Kajubi, the Director, Patent Counsel in the litigation group of Sanofi Canada swore an affidavit asserting that until Hospira had recently filed its Memorandum of Fact and Law in this proceeding it had not asserted that the disclaimer was in any way invalid. He asserts that “to allow Hospira to change its position now to attack the validity of the disclaimer or assert that claims other than the disclaimed claims are in issue is unfair and prejudicial to the Applicant, particularly in light of the liability that the Applicant has potentially accrued in the meantime under s. 8 of the Regulations.”
ISSUES
[74] The following are the issues that arise in this proceeding:
1. Whether the justification of Hospira’s allegations are determined with reference to the claims of the patent as they read when it served its NOA or as they read as at the date of the hearing which was after the disclaimer had been filed;
2. Whether Hospira is estopped from arguing the invalidity of the disclaimer;
3. Whether the disclaimer is valid; and
4. Whether none of Hospira’s allegations are justified.
1. Whether the Court looks at the claims as they read when the NOA was served or at the date of hearing
[75] Subsection 6(2) of the NOC Regulations requires the Court to issue a prohibition order if “it finds that none of those allegations is justified.” Hospira submits that when making that determination the Court is to examine the claims of the patent as at the date the NOA was served. Sanofi Canada submits that when making that determination the Court is to examine the claims of the patent as at the date of hearing. If Hospira is correct, we look to the claims of the ‘778 patent as originally filed. If Sanofi Canada is correct we look to the claims of the ‘778 patent after the disclaimer.
[76] Hospira relies on three recent decisions of this Court which have held that a di