Alcon Canada Inc. v. Cobalt Pharmaceuticals Company

Alcon Canada Inc. v. Cobalt Pharmaceuticals Company
Court (s) Database
Federal Court Decisions
Date
2014-05-14
Neutral citation
2014 FC 462
File numbers
T-972-12
Notes
A correction was made on November 21, 2014
Decision Content
Date: 20140514
Docket: T-972-12
Citation: 2014 FC 462
BETWEEN:
ALCON CANADA INC., ALCON PHARMACEUTICALS, LTD. and BAYER INTELLECTUAL PROPERTY GmbH
Applicants
and
COBALT PHARMACEUTICALS COMPANY and THE MINISTER OF HEALTH
Respondents
REASONS FOR JUDGMENT
Page
I. INTRODUCTION.. 2
II. BACKGROUND.. 4
III. THE 114 PATENT. 9
A. The Applicants’ Evidence. 10
B. Cobalt’s Evidence. 11
C. Analysis. 12
(1) Person of Skill 12
(2) Claim Construction. 15
(a) Promise of the Patent 18
(3) Sound Prediction and Utility. 23
(a) Moxifloxacin is different from Example 15. 26
(b) Example 15 is not identified as the preferred compound. 27
(c) Disclosure of the 114 Patent 29
(4) Obviousness. 36
(a) Introduction. 36
D. Conclusion. 43
IV. THE 211 PATENT. 44
A. The Applicants’ Evidence. 45
B. Cobalt’s Evidence. 46
C. Points in Issue. 46
D. Analysis. 47
(1) Claim Construction. 47
(2) Skilled Person. 50
E. Common General Knowledge. 51
F. Obviousness. 57
G. Conclusion. 60
V. THE 418 PATENT. 61
A. The Applicants’ Evidence. 62
B. Cobalt’s Evidence. 63
C. Claim Construction. 63
D. Skilled Person. 67
E. Infringement 68
F. Analysis. 73
G. Conclusion. 78
SCHEDULE.. 79
PHELAN J.
I. INTRODUCTION [1] This is an application pursuant to s. 55.2(4) of the Patent Act and s. 6 of the Patented Medicines (Notice of Compliance) Regulations SOR/93-133 by Alcon Canada Inc., Alcon Pharmaceuticals Ltd. and Bayer Intellectual Property GmbH GP [the Applicants] for an order prohibiting the Minister of Health from issuing a Notice of Compliance [NOC] to Cobalt Pharmaceuticals Company [Cobalt] for its generic version of the drug Vigamox. The generic version is referred to here as the “Cobalt Product”.
[2] Vigamox is an antibacterial eye drop containing moxifloxacin hydrochloride, an antibacterial agent belonging to the fluoroquinolone class. It is covered by Canadian Patents 1,340,114 [the 114 Patent], 2,342,211 [the 211 Patent] and 2,192,418 [the 418 Patent]. Vigamox is the most commonly used antibacterial eye drop during cataract surgery.
[3] The 114 Patent claims a class of quinolone compounds which includes moxifloxacin characterized by a fused pyrrolidine bicycle at the C-7 position of the quinolone ring. Cobalt admits that its product will infringe the 114 Patent, but argues the 114 Patent is invalid on the basis of a lack of sound prediction and utility. Although in written submissions Cobalt also alleged obviousness, this basis of invalidity was largely abandoned in oral argument.
[4] The 211 Patent claims the use of moxifloxacin hydrochloride in an ophthalmic formulation for the treatment and prevention of bacterial infections, as well as the formulation itself. Cobalt concedes that some claims in the 211 Patent will be infringed by its product. It submits that the patent is invalid on the basis of obviousness and anticipation.
[5] The 418 Patent claims the monohydrate form of moxifloxacin, along with the prism crystalline form of the monohydrate. The parties agree that the Cobalt Product itself will not infringe the 418 Patent, but the Applicants argue that the process for making the Cobalt Product will infringe. Cobalt disputes this and alleges that the patent is invalid for obviousness, lack of sound prediction, ambiguity and inadequate disclosure. Its oral submissions focused on infringement.
II. BACKGROUND [6] Quinolones have been known as antibacterial agents since the 1960s. Quinolones exert their antibacterial effect by interfering with DNA gyrase so as to prevent bacterial DNA from unwinding and duplicating, thereby preventing DNA driven processes in the bacteria. Fluoroquinolone are quinolone compounds which contain a fluorine atom.
[7] The core structure of the quinolones is:
[8] The positions numbered on the core are identified as C-1 to C-8. It is to each of these points that chemical substituents can be attached. In the present case the position of C-7 is critical.
[9] Chemical modifications to the core structure influence the type and level of antibacterial activity. When new quinolones are developed by pharmaceutical researchers, they are evaluated for their antibacterial activity against various bacteria. Bacteria are often classified as Gram-positive and Gram-negative depending on their response to a procedure known as Gram “staining” (Gram happened to be the name of the individual who came up with this process).
[10] The standard approach to evaluating the antibacterial activity of an antibacterial agent is to determine the “minimum inhibitory concentration” [MIC] against bacterial organisms in vitro. The MIC value is the lowest concentration of a compound that will inhibit the visible growth of bacteria after overnight incubation. The lower the MIC value, the more potent a compound is in terms of antibacterial activity. MIC methods are commonly used by medicinal chemists and microbiologists in comparative testing of new antibacterial agents.
[11] The first marketed quinolone was nalidixic acid, which was synthesized in the early 1960s. Nalidixic acid was active against Gram-positive and Gram-negative bacteria, but its use was limited by the high incidence of adverse effects. Even today, toxicity concerns continue to plague the quinolone family and a number of initially promising quinolone candidates have been abandoned due to toxicity. Clinafloxacin is one such example.
[12] Modification of the quinolone structure lead to the development of ciprofloxacin by Bayer in the early 1980s. There are numerous cases involving this compound. Ciprofloxacin had strong antibacterial activity against Gram-negative and Gram-positive organisms, as well as favourable pharmacokinetics for the treatment of system infections. Compared to other quinolones, it had relatively low potential for adverse effects. These advantages lead to ciprofloxacin becoming the industry standard for the treatment of systemic infections by the late 1980s.
[13] Ciprofloxacin was licensed from Bayer by Alcon and incorporated into an antibacterial ophthalmic solution marketed as Ciloxan.
[14] Following the advance of ciprofloxacin into the development phase in 1982, Bayer began to search for a successor quinolone. Researchers at Bayer synthesized new quinolones which were subjected to microbiological testing. The first stage of the testing involved determining the minimum inhibitory concentration [MIC] against bacterial organisms in vitro. Compounds which had positive initial MIC results went on to more rigorous testing including in vivo, toxicity and pharmacokinetic tests.
[15] During the course of this research, Bayer discovered that quinolones with a fused pyrrolidine bicycle at the C-7 position of the quinolone ring showed promise. In July 1988 Bayer filed a German patent application in respect of compounds with this substituent. The Canadian application was filed in July the following year. Moxifloxacin is included in claimed compounds, specifically claims 8 and 13. It had not been synthesised or tested at this point and would not be until 1993.
[16] In 1994 Bayer attempted to develop a tablet formulation of moxifloxacin hydrochloride and encountered two problems. First, the material did not “flow”. Second, formulators were unable to maintain a consistent amount of the active ingredient in the manufactured tablet. Further investigation revealed that the moxifloxacin monohydrate was more stable than the anhydrous form, and that the prism crystalline form of the monohydrate was more free-flowing than the needle crystalline form. Bayer applied for the 418 Patent in Canada on December 9, 1996, which claimed the moxifloxacin hydrochloride monohydrate having particular characteristic peaks in the X-ray powder diffractogram [XRPD] and in solid state NMR testing, along with the prism crystalline form. Bayer went on to develop a moxifloxacin tablet branded as Avelox for the treatment of systemic infections.
[17] By the late 1990s Ciloxan had lost its number one position in the antibacterial eye drop market due to solubility problems. While searching for a successor product, Alcon obtained a sample of moxifloxacin from Bayer in 1999. It incorporated the sample into an ophthalmic solution which it tested both in vivo and in vitro. The in vitro testing showed moxifloxacin had strong activity against most of the tested pathogens, but that it was less active than ciprofloxacin against P aeruginosa, a particularly devastating Gram-negative bacteria. However, in vivo testing demonstrated that moxifloxacin’s superior ocular penetration allowed it to treat P aeruginosa as effectively as ciprofloxacin. The testing also revealed that moxifloxacin had better ocular penetration than any other known quinolone and that it posed no toxicity problems in the eye.
[18] Following the testing Alcon obtained a licence for moxifloxacin from Bayer and incorporated it into an ophthalmic solution to be marketed as Vigamox. It applied for the 211 Patent on September 29, 1999. The 211 Patent claims the use of moxifloxacin in a specified concentration in topical ophthalmic formulations for the treatment of eye infections, as well as in the use of moxifloxacin for the preparation of pharmaceutical compositions and the moxifloxacin-containing pharmaceutical composition itself. Vigamox came on the market in 2003.
[19] Cobalt has developed a 0.5% moxifloxacin hydrochloride solution for ophthalmic administration, the Cobalt Product. It filed an Abbreviated New Drug Submission with the Minister of Health seeking a Notice of Compliance and compares the Cobalt Product to Vigamox in order to demonstrate bioequivalence. Cobalt sent a Notice of Allegation on April 2, 2012 to the Applicants, who responded by bringing a Notice of Application in this Court on May 17, 2012.
III. THE 114 PATENT [20] As these Reasons also address two other patents, the issues and analysis for each is set out separately in these reasons.
[21] The parties agree that the Cobalt Product infringes the 114 Patent. Cobalt admits infringement of Claims 8 and 13 which claim moxifloxacin and its stereoisomers and mixtures thereof. Cobalt also admits infringement of Claims 17 and 18 which claim the use of the compounds of the invention in an antibacterial treatment and a medicament containing the compounds of the invention.
[22] Cobalt challenges the validity of the 114 Patent on several grounds. It alleges that the patent has an expansive promise which it fails to live up to and that the utility of moxifloxacin could not have been soundly predicted by the disclosure. It also alleges that the choice of a fused pyrrolidine bicycle substituent at the C-7 position was either obvious or obvious to try. The Applicants, naturally, disagree.
[23] With respect to the validity of the 114 Patent, there are four matters to be addressed in dealing with the patent’s validity:
i. Person or Ordinary Skill in the Art
ii. Claim Construction
a. Promise of the Patent
iii. Utility and Sound Prediction
a. Disclosure
iv. Obviousness
A. The Applicants’ Evidence [24] The Applicants tendered Dr Domagala, Dr Glenschek-Sieberth and Dr Petersen in respect of the 114 Patent.
[25] Dr Domagala is a medicinal chemist with extensive experience in quinolone research. He has presented and published many papers on quinolones, and is co-inventor on multiple patents for new quinolone antibacterial. He testified with respect to how the Skilled Person would interpret the 114 Patent and the allegations of invalidity made against it. His principal conclusions are that Claims 8 and 13 of the 114 Patent claim moxifloxacin (the S,S enantiomer of the claimed compound); that the Cobalt Product will infringe the 114 Patent; that the utility of moxifloxacin was soundly predicted at the time of the 114 Patent and that the inventive concept of the 114 Patent was not obvious.
[26] Dr Glenschek-Sieberth is a research chemist at Bayer Pharma AG. He was trained as a biology laboratory assistant and conducted antibacterial research for many years at Bayer. He is the custodian of all the records of microbiological testing of quinolones archived at Bayer. He provided evidence of Bayer’s internal records corresponding to the Example compounds, as well as records pertaining to moxifloxacin.
[27] Dr. Petersen is a synthetic organic chemist formerly employed by Bayer and one of the inventors of the 114 Patent. He provided evidence regarding the history and testing of the invention of the 114 Patent.
[28] Dr Zhanel is a medical microbiologist who researches antibiotics. He provided evidence with respect to the infringement and validity of the 114 Patent. His principal conclusions are that that the 114 Patent is infringed by the Cobalt Product; that the promise of the 114 Patent is that the compounds have high antibacterial activity in vitro, particularly against Gram-positive organisms, compared to ciprofloxacin; that the utility of moxifloxacin was soundly predicted based on the data shown in the 114 Patent for Example 15 and that the inventive concept was not obvious.
B. Cobalt’s Evidence [29] Cobalt tendered Dr Hoban and Dr Newton as expert witnesses in respect of the 114 Patent. Dr Hoban is a clinical microbiologist. His affidavit addresses Cobalt’s allegation of lack of utility of the 114 Patent, including his understanding of the utility promised by the 114 Patent and the tests, data and information presented in the 114 Patent. His principal conclusions are that the 114 Patent promises that the claimed compounds (a) have broad antibacterial spectrum, (b) are useful against resistant bacteria, (c) are useful in human and veterinary medicine, (d) are useful for the treatment of bacterial diseases, and (e) are useful for preserving inorganic and organic materials. He further opined that the utility of the claimed compounds is not demonstrated by the data disclosed in the 114 Patent; that the utility of moxifloxacin in particular is not demonstrated, nor is there a basis for soundly predicting its utility and that the inventors of the 114 Patent omitted unfavourable MIC data for the claimed compound.
[30] Dr Newton is a medicinal chemist. His affidavit addresses Cobalt’s allegations of invalidity of the 114 Patent, including his understanding of the subject matter disclosed and claimed in the 114 Patent and obviousness. His principal conclusion is that the inventive concept [the C-7 substituent] was known in the art and obvious.
[31] All of the experts were well qualified and adhered to the experts’ undertaking to the Court. However, in regards to the conflicting expert evidence regarding this 114 Patent, I found the Applicants’ witnesses to be generally preferred. The evidence, both individually and read as a whole, was more consistent internally and externally. Therefore, except as stated otherwise, I have accepted the Applicants’ expert evidence over the Respondent.
C. Analysis (1) Person of Skill [32] An essential component of a contested patent analysis is to determine to whom the teachings in the patent are directed and what level of skill is relevant to an understanding of the patent and related science and common general knowledge.
[33] Alcon submits that, based on its experts’ evidence, the 114 Patent is addressed primarily to a medicinal chemist or a scientist with a medicinal chemistry background having earned at least a masters degree in a related discipline. The Skilled Person would have at least five years of post-graduate experience designing and synthesizing new chemical molecules, at least two years of which relate to working with compounds of the quinolone class, with knowledge or experience in the evaluation of new bacterial compounds. The Skilled Person would also be knowledgeable about the use of SAR studies in the quinolone field and would be familiar with the literature on quinolones during the relevant time frame. There are also minor aspects of the 114 Patent directed to a microbiologist.
[34] Cobalt submitted that the Skilled Person is a member of a multidisciplinary team that includes medicinal chemists and microbiologists.
[35] The medicinal chemist on the team would have a PhD in chemistry, and at least two or three years of post-graduate experience or experience working in the pharmaceutical industry. The medicinal chemist would know how to make modifications to existing molecules to create new members for any particular family and know the expected physical, chemical and biological characteristics of such a family. The skilled team would be familiar and experienced with other formulation, manufacture and testing of pharmaceutical dosage forms.
[36] The definition of the Skilled Person is as much a legal construct as the tort’s “man on the Clapham omnibus” applied to patent law. None of the experts providing opinions in this case come close to this Skilled Person; they are so much higher in the training, experience and education scale.
[37] Given that this case deals with obviousness and utility, the Skilled Person (even if an amalgam of talents) is a person who would work the patent in a real sense.
[38] The key differences between the parties on the Skilled Person is (a) the concept of a team; (b) the nature of experience with Alcon arguing that the medicinal chemist must have experience synthesizing new chemical molecules in the quinolone class; and (c) the necessity of knowledge about the use of SAR studies in the quinolone field as well as with quinolones generally.
[39] I am persuaded that experience with quinolones and SAR studies would be important. I do not discount the legitimacy of a team approach. Therefore, the Skilled Person would be a team led by a medicinal chemist with a microbiologist. The medicinal chemist would have several years of post-graduate experience with exposure to chemical molecules and knowledge of SAR studies in the quinolone field as well as experience generally with quinolones. The microbiologist would have experience testing new compounds for antibacterial activity.
[40] The Court’s approach is similar to that taken in the parallel action in the United States but with a few differences in the Skilled Person description (Alcon, Inc v Teva Pharmaceuticals USA, Inc, 664 F Supp 2d 443 at 454-455, (D Del 2009). It is noteworthy that Dr. Petersen, an Alcon expert and inventor in the 114 Patent, was a chemist-microbiologist.
(2) Claim Construction [41] The 114 Patent claims a novel class of quinolones distinguished by a fused pyrrolidine bicycle at the C-7 position of the quinolone ring. The class is said to have high antibacterial activity, particularly against Gram-positive bacteria.
[42] Moxifloxacin is claimed in Claims 8 and 13 of the 114 Patent. Claim 8 claims all four stereoisomers of the moxifloxacin molecule while Claim 13 is restricted to the two “cis” isomers. Moxifloxacin is the enantiomerically pure S,S compound.
[43] To show that the claimed compounds have high antibacterial activity, the 114 Patent discloses the MIC values of several compounds [the Example compounds] tested against approximately ten bacteria species. MIC data for ciprofloxacin is also provided for the purpose of comparison. Moxifloxacin is not an Example compound, although it closely resembles Example 15. The only difference is that moxifloxacin has a methoxy group at the C-8 position, whereas Example 15 has a fluorine group in that position.
[44] The description section of the 114 Patent refers to a number of aspects which Cobalt contends are essential elements. There is a single reference to low toxicity, a list of pathogens which the claimed compounds are said to be active against, and a list of medical conditions which the compounds are said to be useful in the prevention or treatment thereof. Cobalt has interpreted these references as establishing essential elements of the claim, that is to say it is essential that each of the claimed compounds will have low toxicity, will be active against the named bacterial and will be useful in the treatment or prevention of the listed conditions. I disagree.
[45] There is no dispute on the legal principles applicable to claim construction. It is a matter of law to be performed by the judge with assistance of the Skilled Person but not dictated by the Skilled Person or the expert opinions. The words used in a patent must be looked at and understood “through the eyes and with the common knowledge of a worker of ordinary skill in the field to which the patent relates” (Whirlpool Corp v Camco Inc, 2000 SCC 67, [2000] 2 SCR 1067, at para 53 [Whirlpool]; Bell Helicopter Textron Canada Ltée v Eurocopter, 2013 FCA 219, 449 NR 111, at para 74 [Bell Helicopter]).
[46] An informed and purposive construction of claim language must be made having regard for the patent specification and to the common general knowledge of the Skilled Person as of the date of publication of the patent (Whirlpool, at para 48, 52-55; Free World Trust v Électro Santé Inc, 2000 SCC 66, [2000] 2 SCR 1024, at para 31 [Free World Trust]).
[47] The key to a purposive construction of patent claims is the identification by the Court of what the inventor considered to be the “essential” elements of the invention, while distinguishing what is non essential (Bell Helicopter at para 84; Whirlpool at paras 45-47; Free World Trust at para 31).
[48] On this issue in particular, I have found the evidence of Dr Domgala and Dr Zhanel, experts for Alcon, to be very helpful. Dr Domgala is a medicinal chemist with considerable experience with quinolones and experience working with a competitor of both parties trying to do what Alcon claims to have done.
Dr Zhanel is an experienced microbiologist whose views, in conjunction with Dr Domagala, were clear, concise (as consise as an NOC can be) and cogent.
[49] Based on the expert evidence, the essential elements of Claim 1 of the 114 Patent are:
i. a chemical structure described in Formula (1) having a fused pyrrolidine bicycle at the 7 position of the quinolone molecule; and
ii. a broad spectrum antibacterial activity.
Formula (1) is depicted by the following structure:
[50] Claim 1 of the 114 Patent claims quinolone derivatives of Formula (1) which, Cobalt claims, comprises 111 billion compounds. Claims 8 and 13 (attached as a schedule to these Reasons) are directed at compounds having the same structural formula which include the compound moxifloxacin. These are the claims which Cobalt admits it will infringe. Claim 8 refers to four stereoisomers and Claim 13 refers to two stereoisomers. One of the compounds covered by each of the claims is moxifloxacin.
Because Claims 8 and 13 include hydrochloride salts of the compounds claimed in all hydrate forms, Claims 8 and 13 claim as one of its compounds Moxifloxacin hydrochloride.
[51] Claim 17 covers the use of any of the compounds covered in Claims 1 to 13 for treating a bacterial infection in the human or animal body.
Claim 18 covers any medicament containing any of the compounds of Claims 1 to 13, and their hydrants and salts, where the medicament also contains a dilutent or a carrier (i.e. any vehicle or formulation for administering the compound to a human or an animal, such as a salt).
[52] The bulk of the 114 Patent relates to the synthesis of the new compounds of the invention through several examples, including how to make the C-7 side chains as starting materials and how to attach them to the quinolone core.
(a) Promise of the Patent [53] Much of the argument on the issue of sound prediction turns on the construction of the promise of the 114 Patent.
[54] Cobalt argues that the 114 Patent promises that the claimed compounds will be therapeutically active against a long line of diseases, while exhibiting low toxicity and a broad spectrum of antibacterial action against Gram-positive and Gram-negative bacteria when formulated into a medicament. Cobalt focuses particularly on “low toxicity” and “high activity”.
[55] In contrast, the Applicants construe the promise of the patent as a promise of high antibacterial activity in vitro, especially against Gram-positive bacteria; nothing more. They submit that the Skilled Person would not interpret the patent as promising low toxicity based on a single reference, especially in light of the considerable reputation of quinolones for toxicity problems. Nor they contend, would the Skilled Person understand the patent to promise activity against all known bacteria or resistant bacteria. The references to pharmaceutical use or use as a preservative would be understood by the Skilled Person as statement as potential uses or goals, not as promises.
[56] Both parties rely on Apotex Inc v Sanofi-Aventis, 2013 FCA 186, 230 ACWS (3d) 851 [Plavix] for the proposition that if a patent contains a promise, the promise must be explicit and measurable. If there is no promise, the issue becomes whether there is a scintilla of utility.
[57] Cobalt submits that the patent promises that each of the claimed compounds will:
a. have low toxicity;
b. exhibit antibacterial activity against a broad spectrum of bacteria;
c. be useful in human and veterinary medicine for the prevention, treatment and cure of local and systemic infections caused by bacteria; and
d. be useful as a preservative for inorganic and organic materials.
[58] This construction is based on a single reference to low toxicity and to use as a preservative, a list of pathogens and medical conditions and references to medicaments and/or pharmaceutical compositions.
[59] Cobalt bases its argument that the patent promises that each of the claimed compounds will exhibit antibacterial activity against a broad spectrum of bacteria on the following passage:
For example, local and/or systemic diseases caused by the following pathogens or by mixtures of the following pathogens can be treated and/or prevented:
Gram-positive cocci, for example Staphylococci (Staph. Aureus and Staph. Epidermidis) and Streptococci (Strept. Agalactiae, Strept. Faecalis, Strept. Pneumoniae and Strept. Pyogenes); Gram-negative cocci (Neisseria gonorrhoeae) and Gram-negative rod-shaped bacilli, such as Enterobacteriaceae, for example escherichia coli, Haemophilus influenzae, Citrobacter (Citrob. Freundii and Citrob. divernis), Salmonella and Shigella; and furthermore Klebsiella (Klebs. Pneumoniae and Klebs. Oxytoca), Enterobacter(Ent. Aerogenes and Ent. Agglomerans), Hafnia, Serratia (Serr. Marcescens), Proteus (Pr. Mirabilis, Pr. Rettgeri and Pr. Vulgaris), Providencia and Yersinia, and the genus Acinetobacter. The antibacterial spectrum moreover includes the genus Pseudomonas (Ps. Aeruginosa and Ps. Maltophilia) as well as strictly anaerobic bacteria, such as, for example, Bacteroides fragilis, representatives of the genus Peptococcus, Peptostreptococcus and the genus Clostridium; and furthermore Mycoplasma (M. pneumoniae, M. hominis and M. urealyticum) and Mycobacteria, for example Mycobacterium tuberculosis.
[60] That argument cannot be sustained. The word “example” in the above passage is sufficient to show that not every claimed compound is promised to be effective against all the list pathogens or in relation to all the listed diseases. The most that can be said is that all of the claimed compounds have some degree of antibacterial activity but not against all listed pathogens.
[61] I am not persuaded by Dr Hoban’s attempt to inject a meaning that the compounds would kill all the listed bacteria, some unlisted, and therefore eliminate virtually all bacteria. This is an unduly broad and unnecessary reading of the words undermined by Dr Hoban’s lack of experience reading and interpreting patent claims. Dr Hoban stands alone in his approach.
[62] Given Alcon’s expert evidence, it is more reasonable to interpret “broad spectrum” to mean that the compound hits some Gram-positive and some Gram-negative bacteria across a range of bacteria. I therefore reject Cobalt’s interpretation.
[63] Cobalt has also argued that the 114 Patent promises that each of the claimed compounds will have low toxicity. It bases its argument of promise of low toxicity on the following single reference to low toxicity in the patent:
“The compounds according to the invention, while having a low toxicity, exhibit a broad antibacterial spectrum against Gram-positive and Gram-negative germs.”
[64] In my view, if it was intended to make a promise of low toxicity, the patent would have been drafted to make the promise more explicit. Even the use of “a low toxicity” suggests a potential characteristic or attribute. However, the phrase is used as a comparator and there is no indication of “low toxicity” in comparison to any other toxicity.
[65] The notion of toxicity relates to safety and potential commercial success; not patentability. As held in Apotex Inc v Wellcome Foundation Ltd, 2002 SCC 77, [2002] 4 SCR 153 [AZT], proof of lack of toxicity at this stage of analysis is not necessary to show utility.
[66] I reject Cobalt’s characterization of the promise of the patent. It is based in large part on the affidavit of Dr Hoban, who stated that reading patents was “quite new” to him. I prefer the evidence of Dr Domagala who, in addition to being very familiar with the quinolone field, is co-inventor of a number of patents himself and therefore familiar with their interpretation. Dr Domagala testified that the Skilled Person would interpret the 114 Patent to promise only that “the new quinolone compounds have potent antibacterial activity in vitro against a broad spectrum of bacterial organisms, and in particular against Gram-positive bacteria.” The references to low toxicity, pharmaceutical use and use as a preservative are descriptions of hopes or potential uses, not promises.
[67] Given the care with which most patents are drafted, it is difficult to conceive of the inventors as intending to make a promise on such generalized words appearing but once in the patent. If it was intended to be a promise, it was made without the required supporting data. There is no suggestion that any data was inadvertently omitted.
[68] In light of the finding in Consolboard Inc v MacMillan Bloedel (Saskatchewan) Ltd, [1981] 1 SCR 504, and more recently in Plavix that there is no requirement to make a promise, but if made the patentee is held to it, there is no evidence of advantage to making a promise. To read in a promise in these circumstances would be to inject meaning for the purpose of defeating the 114 Patent.
[69] Therefore, I have rejected Cobalt’s arguments on claim construction and the interpretation of the promise of the patent.
(3) Sound Prediction and Utility [70] Cobalt asserts that the 114 Patent is invalid because its utility was not demonstrated and could not be soundly predicted as of the date on which it was filed, July 13, 1989.
[71] Much of Cobalt’s submissions on the issue of utility are premised on an erroneous construction of the promise. As discussed above, I reject Cobalt’s construction of the promise. To the extent the patent promises anything, it is limited to a promise that the class as a whole will have in vitro activity against a broad spectrum of bacteria. Accordingly, based on Plavix the question becomes whether there is a scintilla of utility.
[72] The question of utility, as raised in the NOA and as argued in this Court, are:
i. Could the utility of the moxifloxacin be soundly predicted on the basis of Example 15?
ii. Was the disclosure adequate?
[73] As moxifloxacin was not synthesized or tested until December 1993, the Applicants have conceded that its utility was not demonstrated at the filing date.
[74] The issue therefore turns on sound prediction. The test for sound prediction was set in AZT at para 70. To paraphrase Justice Binnie at paragraph 70, the doctrine of sound prediction has the following three components:
a. There must be a factual basis for the prediction;
b. The invention must have at the date of the patent application an articulable and sound line of reasoning from which the desired result can be inferred from the factual basis; and
c. There must be proper disclosure, which is to say that the patent must provide a full, clear and exact description of the nature of the invention and the manner in which it can be practiced.
[75] In Apotex Inc v Sanofi-Aventis, 2013 FCA 186, 447 NR 313, the Court of Appeal set out a useful summary of the principles at play in an allegation of inutility.
46 A patent holder whose patent is challenged on grounds of lack of utility must be able to show that, at the time of the patent was applied for, the utility of the invention could either be demonstrated or soundly predicted: see AZT, at paragraph 46. The sticking point, in this case as in others, is to determine what it is that must be demonstrated or soundly predicted. This is where the notion of the promise of the patent comes into play.
47 The promise of the patent is the standard against which the utility of the invention described in the patent is measured. The source of the concept is found in the decision of the Supreme Court of Canada in Consolboard:
There is a helpful discussion in Halsbury's Laws of England, (3rd ed.), vol. 29, at p. 59, on the meaning of "not useful" in patent law. It means "that the invention will not work, either in the sense that it will not operate at all or, more broadly, that it will not do what the specification promises that it will do".
Consolboard, cited above at p. 525
48 While an inventor need not describe the utility of his invention in his patent, if he does so, he will be held to the promise which he has made. This was set out as follows in Olanzapine, cited above, at paragraph 76:
Where the specification does not promise a specific result, no particular level of utility is required; a "mere scintilla" of utility will suffice. However, where the specification sets out an explicit "promise", utility will be measured against that promise: Consolboard; Pfizer Canada Inc. v. Canada (Minister of Health), [2009] 1 F.C.R. 253, 2008 FCA 108 (Ranbaxy). The question is whether the invention does what the patent promises it will do.(emphasis in the original)
49 If the inventor does not make an explicit promise of a specific result, the test for utility is a "mere scintilla" of utility. If, on the other hand, the inventor makes an explicit promise of a specific result, then utility will be assessed by reference to the terms of the explicit promise.
50 When this Court said at paragraph 80 of Olanzapine, cited above, that the promise of the patent must be ascertained, it should not be taken to have assumed that every patent contains an explicit promise of a specific result since, subject to what is said below with respect to selection patents, there is no obligation on the part of the inventor to disclose the utility of his invention in the patent. In Olanzapine, the Court was simply indicating that the firs step in assessing utility was to determine the standard against which utility will be measured. This requires the Court to construe the patent to determine if a person skilled in the art would understand it to contain an explicit promise that the invention will achieve a specific result. If so, the inventor will be held to that promise. If there is no explicit promise of a specific result, then a mere scintilla of utility will do.
[76] Cobalt submits that moxifloxacin’s utility could not have been soundly predicted based on Example 15 as claimed by the Applicants for two reasons. Firstly, moxifloxacin differs from the Example 15 compound in the substituent at the C-8 position.
[77] Secondly, Example 15 is not identified in the patent as the preferred compound. The 114 Patent did not identify Example 15 as preferred over the other tested compounds; in Cobalt’s submission, this results in a lack of proper disclosure of the factual data relied on by the patentee, the third part of the sound prediction test set in AZT.
(a) Moxifloxacin is different from Example 15 [78] The basis for the prediction of utility of Claims 8 and 13 is the MIC test results in the patent for Example 15. Example 15 is structurally very similar to the compounds of Claims 8 and 13. The only difference is in the substituent at position C-8.
[79] Moxifloxacin differs from Example 15 only in respect of the C-8 substitutent; moxifloxacin has a methoxy group at that position, while Example 15 has a fluorine. The Applicants submit that it was common general knowledge that compounds with a methoxy group at the C-8 position were active. They rely on European Patent Application No 0 241 206 [Sankyo] and European Patent 0 230 295 A2 [Kyorin] as examples of prior art teaching that compounds with a methoxy group at the C-8 position had good activity. The inventors therefore had a sound basis to predict that substituting a methoxy group at that position for the fluorine in Example 15 would either enhance or not hinder the high antibacterial activity demonstrated by Example 15.
[80] The Applicants further submit that the data disclosed for Example 15 provided a basis to soundly predict the activity of the individual enantiomers. They rely on prior art by Matsumoto and Domagala to the effect that chirality which is further from the quinolone core has little effect on activity. Therefore, the prediction of good activity is sound for all the enantiomers
[81] The Applicants rely on Fournier Pharma Inc v Canada (Minister of Health), 2012 FC 740, 413 FTR 239, for the proposition that a patentee is not limited to specific compounds that he or she has actually made and tested prior to filing for patent protection, so long as what is claimed is based on a sound prediction. Quoting from Justice MacTavish in Aventis Pharma Inc v Apotex Inc, 2005 FC 1283, 278 FTR 1, at para 156, Justice Zinn wrote at para 148:
The law is clear that a patentee is not to be limited to specific compounds that he or she has actually made and tested prior to filing for patent protection. A patentee is able to claim more broadly, so as to cover a class of compounds, as long as the claim is based upon a sound prediction.
(b) Example 15 is not identified as the preferred compound [82] They submit that the Skilled Person would have readily observed that Example 15 was the most active of the tested compounds. They submit that the Skilled Person would have considered the panel of organisms tested to be a well-chosen and representative sample of common and clinically important bacteria, with varying susceptibility to ciprofloxacin. The MIC test method reported in the 114 Patent was and remains a well-accepted method for determining whether a compound has antibacterial activity. Cobalt’s expert Dr Hoban admitted this in cross examination.
[83] It is noteworthy that Example 15 had lower MIC values than ciprofloxacin against certain bacteria. However, not all MIC test results were better than ciprofloxacin but there is no evidence that they were not effective as compared to some other Example compounds.
[84] Cobalt argues that the 114 Patent promises that the claimed compounds will have superior activity to ciprofloxacin. As found earlier, there is no such promise but by expanding the promise Cobalt gains the advantage that there was no sound basis to predict. The theory is that the greater the promise, the weaker the sound prediction.
[85] However, if there is a promise, it is more limited than suggested. Further, I accept the expert evidence that low MIC scores is an indicator that the compounds would be effective in vivo; that a Skilled Person would have a sound basis for prediction and that if there was a promise, the tests would be sufficient to demonstrate any promise based on the MIC data provided for Example 15.
[86] I approach Dr Hoban’s evidence with some caution. He appears to have approa