Alcon Canada Inc v Cobalt Pharmaceuticals Company, 2014 FC 149
The Federal Court dismissed Alcon Canada Inc.’s application to restrain the Minister of Health from issuing a Notice of Compliance to Cobalt Pharmaceuticals Company for approval to sell its generic version of an eye and nasal drop solution that Alcon contended would infringe its Canadian Patent No. 2,447,924 (the ‘942 Patent). [1,3, 241] The application was dismissed after the Court determined that the ‘942 Patent lacked the evidence to demonstrate or soundly predicted its utility and contained overbroad claims. [222, 228] The Court examined in detail a number of experiments disclosed in the patent that were said to establish the claimed utility, but the experiments did not demonstrate or soundly predict utility for the broad ranges of molecular weight and chemical concentration claimed. [199, 205] Claims of obviousness, ambiguity, and insufficiency were argued, but were each rejected.
Claim Construction and Inventive Step [18-52]
The ‘924 Patent is directed generally towards the ability of polyvinylpyrrolidone (“PVP”) to physically stabilize an olopatadine eye drop or nasal solution. [9] The ‘924 Patent also teaches that there are five excipients that should be excluded from the solution. [23] These five excipients are listed in the claims below.
Claims 2 and 7 were at issue. The Court rephrased claims 2 and 7 by incorporating language from claims 1-6 from which they depend:
2. A topically administrable solution composition for treating allergic or inflammatory disorders of the eye and nose comprising 0.18 – 0.22% (w/v) olopatadine and PVP in an amount sufficient to enhance the physical stability of the solution, wherein the composition does not contain polyvinyl alcohol, polyvinyl acrylic acid, hydroxypropylmethyl cellulose, sodium carboxymethyl cellulose or xanthan gum.
7. A topically administrable solution composition for treating allergic or inflammatory disorders of the eye and nose comprising 0.17 – 0.62% (w/v) olopatadine wherein the solution comprises 1.5 – 2% (w/v) PVP having a weight average molecular weight of 5000 – 1,600,000, wherein the composition does not contain polyvinyl alcohol, polyvinyl acrylic acid, hydroxypropylmethyl cellulose, sodium carboxymethyl cellulose or xanthan gum. [22]
Both parties concurred with this paraphrasing, but disagreed on three terms: (1) the molecular weight of PVP used in claim 2, and the interpretation of (2) “amount sufficient”, and (3) “enhance” in claim 2. [34]
After claim construction, the molecular weight of PVP was taken to be in the range of 5kD to 1600kD, since claim 1 from which claim 2 depends was also subject to that range. [40] The term “amount sufficient” was taken to mean the amount of PVP that is sufficient to enhance the physical stability of the solution as compared to an identical solution not containing PVP. [41] The term “enhance” was taken to mean to “improve” the stability of a solution in most instances as compared to solutions that are PVP-free but otherwise identical, but not to guarantee a more stable solution in all instances. [45-46]
The Court determined the inventive concept of claims 2 and 7 to be that “PVP at sufficient concentrations improves the physical stability of higher concentration (0.2% to 0.6%) olopatadine solutions in most instances”, and “whereas the five excluded excipients do not.” [52]
The Promises of the ‘924 Patent [53-66]
The Court identified three distinct promises that the ‘924 Patent makes.
First, claim 2 promises that “PVP having an average molecular weight of 5000 to 1600K (and most preferably 50K – 60K), and at sufficient concentrations will enhance the physical stability of 0.18 – 0.22% (w/v) olopatadine solutions.” [54] The disclosure describes the sufficient concentrations of PVP as “0.1 – 3%, preferably 0.2 – 2%, and most preferably 1.5 – 2%,” [55] but the promise was taken to apply to the broadest range, 0.1-3%. [66] The promise is effectively a broad range of PVP stabilizing a narrow range of olopatadine solutions.
Secondly, claim 7 promises that “PVP having an average molecular weight of 5000 to 1600K (and most preferably 50K – 60K), and at concentrations of 1.5 – 2% will enhance the physical stability of 0.17 – 0.62% (w/v) olopatadine solutions.” [54] This promise is effectively a more narrow range of PVP stabilizing a broader range of olopatadine solutions.
Third, the patent promises that “the five excluded excipients do not enhance stability, or at least, not as well as PVP.” [62]
The ’924 Patent was not Obviousness [67-120]
After determining the common general knowledge of the person skilled in the art, [81] the Court determined that the claimed invention was not obvious and not obvious to try. [120] Although the prior art indicated that PVP could enhance the physical stability of an ophthalmic formulation, it said nothing about the ability of PVP to perform this function in an olopatadine solution, and said nothing about the ineffectiveness of the five excluded excipients. [111, 119] The use of PVP as opposed to the five excluded excipient was not self-evident, as was confirmed by testimony of both experts, [115] and the solution was not arrived at until several rounds of experiments were conducted. [116] Notably, however, the Court would later determine that at least some of these experiments disclosed in the specification did not demonstrate or soundly predict the claimed utility of the invention.
The Disclosed Experiments did not Demonstrate or Soundly Predict Utility [122-122]
The ‘924 Patent contained a number of typographical and clerical errors in the disclosure of the experiments that were said to demonstrate the invention’s utility. [133] The Court accepted corrections to these errors, but in turn it also decided that Cobalt’s NOA must be read generously. [139] As a result, Cobalt was able to dispute the utility of any of the experiments in the disclosure, not limited to the ones mentioned in its NOA. [140]
The disclosure in the ‘924 Patent provides 5 examples (numbered 5, 7, 9, 10 and 11) that are relevant to the utility inquiry. [142]
Example 5 compared stability of solutions containing PVP at a relatively high concentration (1.0% – 1.8%) to solutions containing the excluding excipients at relatively lower concentrations (0.01% – 0.1%). [143] No control was used. The solutions containing PVP performed better, but the Court found this comparison to be unfair due to the extreme difference in concentration of the excipients and the lack of a control. [149-150]
Example 7 compared different olopatadine solutions containing (1) just PVP, (2) PVP with polyethylene glycol, and (3) just polyethylene glycol in freeze-thaw conditions. [151] The results were mixed: in 0.2% olopatadine solutions, 58kD PVP and 1300kD PVP enhanced the solution’s physical stability, [154] but in 0.3% olopatadine solutions, PVP performed worse than polyethylene glycol alone. [157]
Example 9 tested 0.2% olopatadine solutions with 58kD PVP at concentrations of 0.01% to 1.0%, or with 0.1% 1300kD PVP, under refrigeration and freeze-thaw conditions as compared to a control. [158] The results were again mixed: 58kD PVP at concentrations from 0.1% to 1.0% (not 0.01% – 0.1%) enhance the physical stability of 0.2% olopatadine solutions in refrigeration and freeze-thaw conditions, [168] but 1300kD PVP at 0.1% PVP only showed improvement in free-thaw conditions, not refrigeration conditions. [169]
Example 10 tested 58kD PVP at 1.8% in solutions with increasing concentrations of olopatadine in thermal cycling and short term stability conditions as compared to controls. [170] The experts were in agreement that, on the whole, example 10 indicated that PVP enhances physical stability for stability testing conditions, but not for thermal cycling conditions. [176, 179] However, the results for 0.2% olopatadine (the only concentration claimed in claims 2 and 7) did not demonstrate enhancement of physical stability. [176]
Example 11 tested 58kD PVP at 1.8% in a pH suitable for nasal solutions to demonstrate utility with respect to nasal solutions. [180] However, no control was included, thus, as with example 5, this experiment proved nothing with respect to claims 2 and 7 of the ‘924 Patent. [182]
Claim 2 was found to be neither demonstrated nor soundly predicted by the data disclosed in the ‘924 Patent. [185] The data for the 1300K grade PVP tenuous at best (2 out of the only 6 conditions tested showed failure), [192] and overall the experiments only provided data for PVP with molecular weights of 58kD and 1300kD – too narrow for the claimed range from 5kD to 1600kD. [199-200] Utility over this broader range was also not soundly predicted. [202] An expert opinion merely stating that he thinks the person skilled in the art would be able to extrapolate to the broader range was not sufficient as an articulable and sound line of reasoning, [204-205] which was especially necessary in this case given the unpredictable nature of physical stability relationships. [206-207]
Claim 7 was found to be not soundly predicted for similar reasons. [210] The experiments only provided data relevant to 58kD PVP – far from the claimed 5kD to 1600kD, without disclosing a sound line of reasoning to extrapolate to the wider range. [213-214]
The ‘924 Patent Claims are Overbroad [223-228]
Commenting that Cobalt’s overbreadth argument is simply another way of articulating its argument on utility, the Court similarly found that the claims were drafted too broadly. [227-228]
Ambiguity and Insufficiency [229-240]
On the other hand, Cobalt’s arguments on ambiguity and insufficiency failed. [229] Cobalt argued that the term “amount sufficient” in claim 2 is ambiguous, but the Court rejected the argument, noting that the disclosure specifies the ranges of preferred concentrations. [237-238] Furthermore, fine-tuning the concentration ranges would be a matter of routine experimentation, so disclosing only the ranges could not be said to be insufficient. [239]
Commentary
In this case the Court found promises by reading the functional language of the claims (e.g. “amount sufficient”). This suggests a development beyond the tendency for courts to find promises by reading explicit statements of objective in the specification.
As a practical matter, this case provides guidance for the level of experimental evidence that one should disclose in a patent application to meet the utility requirement for any promised utility. Firstly, it suggests that your patent should not claim ranges (e.g., of concentration of a chemical in solution or molecular weight of a molecular) without including evidence that your invention has utility at the endpoints of those ranges. Secondly, it suggests that experiments without controls are of very little persuasive value. Thirdly, the Court’s comments about the unpredictable nature of physical stability suggest that for more poorly understood areas of science, better evidence is required to demonstrate utility. [214]
This case also sheds light on what can be expected when your patent is challenged for lack of utility, and it is later determined that your patent contains errors in its evidentiary disclosure. Here we saw that Cobalt was able to direct its arguments against any of the experiments disclosed in the patent, even those which were not discussed in its NOA, as a matter of fairness.
One point to ponder for litigation purposes is the disconnect between the Court’s obvious to try analysis and its utility analysis. In its obvious to try analysis, the Court stated that “the evidence does disclose that several rounds of experiments were conducted before the PATADAY formula was perfected”. [116] The Court accepts the rigor and “significant degree of experimentation [that] was conducted in order to achieve the claimed invention” [117] to determine that the invention was not obvious to try, but ultimately determines that the experiments were unable to demonstrate or soundly predict the utility of the invention.