Allergan Inc. c. Canada (Health)

Allergan Inc. c. Canada (Health)
Court (s) Database
Federal Court Decisions
Date
2012-06-18
Neutral citation
2012 FC 767
File numbers
T-1560-10
Notes
Digest
Decision Content
Date: 20120618
Docket: T-1560-10
Citation: 2012 FC 767
Toronto, Ontario, June 18, 2012
PRESENT: The Honourable Mr. Justice Hughes
BETWEEN:
ALLERGAN INC., ALLERGAN SALES INC.
and ALLERGAN, INC.
Applicants
and
THE MINISTER OF HEALTH and
APOTEX INC.
Respondents
REASONS FOR JUDGMENT AND JUDGMENT
[1] This is an application made under the provisions of the Patented Medicines (Notice of Compliance) Regulations SOR/93-133, as amended (NOC Regulations) to prohibit the Minister of Health from issuing a Notice of Compliance to Apotex Inc. for a topical ophthalmic product to be known as APO-BRIMONIDINE-TIMOP, which Apotex has compared to Allergan Inc.’s product known as COMBIGAN, until the expiry of Canadian Letters Patent No. 2,440,764 (the '764 patent) on April 9, 2023. For reasons of comity, the Application is allowed.
[2] For convenience, the topics discussed can be found at the following paragraphs:
INDEX
TOPIC
PARAS
THE PARTIES
3 to 6
THE MEDICINE
7 to 8
THE '764 PATENT
9 to 28
THE EVIDENCE
29 to 33
PREVIOUS FEDERAL COURT DECISION RESPECTING
THE '764 PATENT
34 to 36
PREVIOUS UNITED STATES DECISION
37 to 39
ISSUES
40 to 186
ISSUE #1: Who bears the burden?
42
ISSUE #2: The effect of the earlier Federal Court decision
43 to 82
a) The decision
43 to 65
b) Comity
66 to 68
c) The jurisprudence
69 to 80
d) Conclusion as to effect of the previous Federal Court decision
81 to 82
ISSUE #3: Effect of the United States Decision (Judge Ward)
83 to 100
ISSUE #4: Who is the person skilled in the art?
101 – 108
ISSUE #5: Claim construction
109 to 114
ISSUE #6: Are the claims obvious?
116 to 188
ANTICIPATION AND OBVIOUSNESS
116 to 188
A) Anticipation
119 to 127
B) Obviousness
128 to 188
What is the “Inventive Concept”?
135 to 141
Inventive Concept of Claim 22
142 to 149
Differences between the State of the Art
and the Inventive Concept
150 to 154
Were these differences obvious?
155
1) Is it more or less self-evident that what is being tried ought to work? Is there a finite number of identified predictable solutions known to skilled persons?
156 - 168
2) What is the extent, nature an amount of effort required? Are routine trials carried out or is the experimentation prolonged and arduous, such that the trials would not be considered routine?
169 - 176
3) Is there motive provided in the prior art to find the solution?
177 - 181
4) What was the actual course of conduct that culminated in this invention?
182 -186
5) Commercial Success
187 - 188
CONCLUSIONS AS TO OBVIOUSNESS
189 - 195
THE PARTIES
[3] The Applicant Allergan, Inc (note the comma). is the owner of the '764 patent. The Applicant Allergan Inc. (no comma) is a Canadian pharmaceutical manufacturer which sells the COMBIGAN product in Canada. Allergan Sales Inc. played no active part in these proceedings. I will refer to the Applicants collectively as Allergan.
[4] The Respondent Minister of Health is, among other matters, responsible for granting Notices of Compliance to those wishing to distribute medicines such as those at issue here, in Canada. The Minister has notice of these proceedings but has taken no active part in them.
[5] The Respondent Apotex Inc. is a Canadian corporation which manufactures and distributes generic medicines in Canada. In the present case, it wishes to make and sell an ophthalmic drug called APO-BRIMONIDINE-TIMOP, which is a generic version of Allergan’s COMBIGAN.
[6] In the parlance of the NOC Regulations, Allergan is a “first person”, and Apotex is a “second person”.
THE MEDICINE
[7] The COMBIGAN medicine is a topical ophthalmic solution to treat intraocular pressure (IOP) in persons suffering from chronic glaucoma. In short, it is an eye drop medicine used to treat glaucoma.
[8] In particular, the COMBIGAN medicine is in the form of a liquid solution having two active ingredients; 0.2% by weight/volume of brimonidine, and 0.5% by weight/volume of timolol, together with other pharmaceutically acceptable ingredients (excipients) including a stabilizer known as BAK.
THE '764 PATENT
[9] Canadian Letters Patent No. 2,440,764 (the '764 patent), entitled “Combination of Brimonidine and Timolol for Topical Ophthalmic Use”, were issued and granted to the Applicant Allergan, Inc. on October 25, 2005.
[10] The application for the patent was filed under the provisions of the Patent Co-Operation Treaty (PCT); with an effective filing date in Canada of April 9, 2003. The application and patent are governed by the provisions of the Patent Act, RSC 1985, c. P-4, applicable after October 1, 1989, sometimes called the “new” Patent Act. The term of the '764 patent will expire twenty (20) years from its effective filing date in Canada; that is, on April 9, 2023.
[11] The '764 patent claims a priority date of April 19, 2002, which is the date when a similar application was filed in the United States Patent Office. This is the date upon which the issues of obviousness and anticipation are to be considered.
[12] The application for the '764 patent was laid open for public inspection, through the Patent Co-Operation Treaty, on October 19, 2003. This is the date to be used for construing the patent.
[13] Before reviewing the patent in detail, there a few terms used in the patent and in evidence that require explanation and upon which the parties are agreed. It is agreed that the prior art included the administration of drops to the eye in order to reduce the intraocular pressure (IOP) in the eyeball as a means to treat or control glaucoma. The known active ingredients included either timolol or brimonidine. The drops were often self-administered by the patient. Administration twice a day is referred to as BID. Administration three times a day is referred to as TID. The precise derivation of these terms is not clear in the record but apparently the B stands for bis and the T for ter. On occasion drops of one drug would be administered closely followed (usually in five minutes or so) by drops of the other. This type of administration is sometimes called serial administration or adjuvant administration. On occasion a witness may also refer to this as a combination administration. This is not to be confused with administration of a medicine that includes both drugs in one bottle. This is sometimes referred to by a witness as administration of a combination drug.
[14] The '764 patent begins at page 1 with a statement as to the background of the invention and what the invention does. It acknowledges that two active ingredients, brimonidine and timolol, are known and have been used to treat glaucoma, including the fact that they have been used in serial application (i.e. one after the other). It is important to note what the patent says the need is; and, having regard to the conclusions on page 16 which will be discussed later, what the patent says the invention delivers; this is (a) a composition including both brimonidine and timolol that is (b) effective, (c) safe, (d) has increased stability, and (e) requires a lower effective concentration of preservative as compared to each medicine if taken as a separate dose of each of brimonidine and timolol. It says:
BACKGROUND OF THE INVENTION
This invention relates to the topical ophthalmic use of brimonidine in combination with timolol when indicated for treatment of glaucoma or ocular hypertension. Such combinations or formulations are available for separate use in the ophthalmic art and have been combined in serial application during the course of treatment of glaucoma. However, there are concerns and expressed reservations in the ophthalmic community about patient compliance when the patient is required to administer separate medications to treat a single disease or condition such as glaucoma. There is, moreover, a long felt need for an effective and safe topical ophthalmic pharmaceutical composition including brimonidine and timolol which has increased stability and requires a lower effective concentration of preservative as compared to the individual agents taken alone. Finally, there is a need to increase the efficacy of many topical ophthalmic agents, without increasing the systemic concentration of such topical agents, since it is well known that many of such topically-applied ophthalmic agents cause systemic side effects, e.g. drowsiness, heart effects, etc. Unexpectedly it has been discovered that brimonidine in combination with timolol meets these criteria.
Brimonidine is disclosed in U.S. Patent 3,890,319. The use of brimonidine for providing neuroprotection to the eye is disclosed in U.S. Patents 5,856,329; 6,194,415 and 6,248,741.
Timolol, as an ophthalmic drug, is disclosed in U.S. Patents 4,195,085 and 4,861,760.
[15] At pages 2 and 3 chemical depictions of brimonidine and timolol are provided, which I will not repeat, and indications as to where they may be purchased. Two paragraphs at page 3 provide for more specific dosages but it is to be noted that while one drop two times a day is recommended, the precise regimen is left to the discretion of the clinician:
The compositions of the present invention are administered topically. The dosage is 0.001 to 1.0, e.g. mg/per eye BID; wherein the cited mass figures represent the sum of the two components, brimonidine and timolol. The compositions of the present invention can be administered as solutions in a suitable ophthalmic vehicle.
In forming compositions for topical administration, the mixtures are preferably formulated as 0.01 to 0.5 percent by weight brimonidine and 0.1 to 1.0 percent by weight timolol solution in water at a pH of 4.5 to 8.0, e.g. about 6.9. While the precise regimen is left to the discretion of the clinician, it is recommended that the solution be topically applied by placing one drop in each eye two times a day. Other ingredients which may be desirable to use in the ophthalmic preparations of the present invention include preservatives, co-solvents and viscosity building agents.
[16] At the bottom of page 3 and over to page 4, the description addresses preservatives used to prevent microbial contamination. It acknowledges that benzalkonium chloride (referred to as BAK in these proceedings) is one of the known preservatives and describes, in particular, certain levels of concentration of BAK ( from 0.001% to less than 0.01% e.g. from 0.001% to 0.008% preferably about 0.005% by weight) and dosages (twice a day) of the combination medicine that are advantageous, and that adequate lowering intraocular pressure can be achieved with twice-daily administration of the combination drug as compared to serial administration of Alphagan (brimonidine) and Timoptic (timolol) three times a day:
Antimicrobial Preservatives
Ophthalmic products are typically packaged in multidose form. Preservatives are thus required to prevent microbial contamination during use. Suitable preservatives include: benzalkonium chloride, thimersol, chlorobutanol, methyl paraben, propyl paraben, phenylethyl alcohol, edetate disodium, sorbic acid, Onamer M, or other agents known to those skilled in the art. In the prior art ophthalmic products, typically such preservatives are employed at a level from 0.004% to 0.02%. In the compositions of the present application the preservative, preferably benzalkonium chloride, may be employed at a level of from 0.001% to less than 0.01%, e.g. from 0.001% to 0.008%, preferably about 0.005% by weight. It has been found that a concentration of benzalkonium chloride of 0.005% is sufficient to preserve the compositions of the present invention from microbial attack. This concentration may be advantageously compared to the requirement of 0.01% benzalkonium chloride to preserve timolol in the individual, commercially-available ophthalmic products. Moreover, it has been found that adequate lowering of intraocular pressure has been obtained when administering the compositions of this invention twice a day as compared to the FDA-approved regimen wherein brimonidine ophthalmic solution, i.e. Alphagan® ophthalmic solution is administered three times a day and timolol ophthalmic solution, i.e. Timoptic® ophthalmic solution is administered twice a day. This results in the exposure of the patient to 67% and 50% of benzalkonium chloride, with the compositions of this invention, as compared to the administration of Alphagan® and Timoptic®, respectively. In FDA-approved adjunctive therapy, wherein Alphagan® and Timoptic® are serially administered, the patient is exposed to almost three times the concentration of benzalkonium chloride as compared to the administration of the compositions of this invention twice a day. (It is noted that it is known that benzalkonium chloride at high concentrations is cytotoxic. Therefore, minimizing the patient’s exposure to benzalkonium chloride, while providing the preservative effects afforded by benzalkonium chloride, is clearly desirable.)
[17] At pages 4 and 5, co-solvents and viscosity agents are discussed. This discussion is not relevant to the issues in these proceedings.
[18] Example I at pages 5 and 6 provides for a preparation including 0.20% by weight/volume of brimonidine, 0.68% by weight/volume of timolol maleate, which is equivalent to 0.50% by weight/volume of timolol, and 0.005% by weight/volume of BKC, together with other excipients.
[19] Example II, beginning at page 6 and continuing to the end of the descriptive portion of the patent at page 16, provides extensive information as to the clinical testing of the combination of Example I in twice-a-day dosing in comparison with administration of solutions containing just brimonidine three times a day or just timolol twice a day.
[20] The objectives of the experiment described as Example II are stated at page 6:
To compare the safety and efficacy of twice-daily dosed brimonidine tartrate 0.2% timolol 0.5% ophthalmic solution combination (henceforth referred to as Combination) with that of twice-daily dosed timolol ophthalmic solution 0.5% (henceforth referred to as Timolol) and three-times-daily dosed ALPHAGAN® (brimonidine tartrate ophthalmic solution) 0.2% (henceforth referred to as Brimonidine) administered for three months (plus 9-month masked extension) in patients with glaucoma or ocular hypertension.
[21] The intraocular pressure (IOP) of the participating patients taking each of these doses was periodically measured. At pages 9 to 11, the patent reports the measured values and their statistical significance in respect of efficacy:
Efficacy:
At baseline, mean values of diurnal IOP ranged from 22.2 mm Hg to 24.9 mm Hg in the Combination group, 22.5mm Hg to 25.0 mmHg in the Brimonodine group, and 22.3 mm Hg to 24.8 mm Hg in the Timolol group. There were no statistically significant differences between treatment groups.
Mean changes from baseline diurnal IOP at week 2, week 6 and month 3 ranged from:
-5.2 to -7.9 mm Hg in the Combination group
-3.5 to -5.7 mm Hg in the Brimonidine group
-4.5 to -6.4 mm Hg in the Timolol group
The mean decreases from baseline diurnal IOP were statistically significant within each treatment group at each follow-up timepoint (p<0.001).
The mean decrease from baseline diurnal IOP was statistically significantly greater with Combination that with Brimonidine at hours 0, 2 and 7 at all follow-up visits (p<0.001). In addition, clinically significant differences of more than 1.5 mm Hg in mean change from baseline IOP favoring Combination over Brimonidine were seen at hours 0, 2, and 7 at all follow-up visits. At hour 9, the decreases from baseline diurnal IOP were greater for the Combination group than the Brimonidine group at all follow-up visits, although the differences were not statistically significant (p≥ 0.104).
The mean decrease from baseline diurnal IOP was statistically significantly greater with Combination than with Timolol at hours 0, 2, 7 and 9 at all follow-up visits (p≤ 0.041). In addition, clinically significant differences of more than 1.5 mm Hg in mean change from baseline IOP favoring Combinatin over Timolol were seen at week 2 (hours 0, 2, and 7), week 6 (hours 2 and 7), and month 3 (hours 0 and 2).
Mean values of diurnal IOP at week 2, week 6 and month 3 ranged from:
15.9 to 18.1 mm Hg in the Combinatin group
17.4 to 21.5 mm Hg in the Brimonidine group
17.5 to 18.9 mm Hg in the Timolol group
Mean values of diurnal IOP were statistically significantly less with Combination than with Brimonidine at hours 0, 2, and 7 at all follow-up visits (p<0.001) and at hour 9 at week 6 and month 3 (p≤ 0.011). The mean values of IOP at hour 9 at week 2 were lower for the Combination group than the Brimonidine group, although the difference was not statistically significant (p=0.205). In addition, clinically significant differences of more than 1.5 mm Hg in mean IOP favoring Combination over Brimonidine were seen at hours 0, 2, and 7 at all follow-up visits and at hour 9 at month 3.
Mean values of diurnal IOP were statistically significantly less with Combination than with Timolol at hour 0 at week 2 and month 3; and at hours 2, 7 and 9 at all follow-up visits (p≤ 0.050). The mean values of IOP at hour 0, week 6, were lower for the Combination group than the Timolol group, although the difference was not statistically significant (p=0.102). In addition, clinically significant differences of more than 1.5 mm Hg in mean IOP favoring Combination over Timolol were seen at week 2 (hours 0, 2, and 7), week 6 (hours 2, 7, and 9), and month 3 (hours 2 and 9).
Mean values of diurnal IOP were statistically significantly less with Combination than with Brimonidine at hours 0, 2, and 7 at all follow-up visits (p<0.001) and at hour 9 at week 6 and month 3 (p≤ 0.011). The mean values of IOP at hour 9 at week 2 were lower for the Combination group than the Brimonidine group, although the difference was not statistically significant (p=0.205). In addition, clinically significant differences of more than 1.5 mm Hg in mean IOP favoring Combination over Brimonidine were seen at hours 0, 2, and 7 at all follow-up visits and at hour 9 at month 3.
Mean values of diurnal IOP were statistically significantly less with Combination than with Timolol at hour 0 at week 2 and month 3; and at hours 2, 7 and 9 at all follow-up visits (p≤0.050). The mean values of IOP at hour 0, week 6, were lower for the Combination group than the Timolol group, although the difference was not statistically significant (p=0.102). In addition, clinically significant differences of more than 1.5 mm Hg in mean IOP favoring Combination over Timolol were seen at week 2 (hours 0, 2, and 7), week 6 (hours 2, 7, and 9), and month 3 (hours 2 and 9).
[22] At pages 12 to 14 the patent provides an analysis of the experiment from the point of view of safety. I repeat what is stated at page 12:
Safety:
Through month 3 of the study, 53.4% (103/193) of patients in the Combination group, 61.7% (121/196) of the Brimonidine group, and 50.8% (100/197) of the Timolol group experienced one or more adverse events, regardless of causality. The incidences of oral dryness, eye pruritus, foreign body sensation and conjunctival folliculosis were statistically significantly lower with the Combination than with Brimonidine (p≤ 0.034), while burning and stinging were statistically significantly higher with the Combination than with Brimonidine (p≤ 0.028). There were no statistically significant differences in adverse events between the Combination and Timolol, except for a statistically significantly higher incidence of eye discharge with the Combination (2.6%, 5/193) compared to Timolol (0%, 0/197; p = 0.029).
[23] Commencing at page 14, over to page 16, the patent reports the analysis of the pharmacokinetics of the experiment. I will not set out this portion out as no party referred to this portion of the patent in argument.
[24] The conclusions are stated at page 16. They conclude that the combination of brimonidine and timolol administered twice a day (BID) was superior to just timolol administered twice a day (BID) or just brimonidine administered three times a day (TID) in lowering interocular pressure (IOP) and delivered a safety profile comparable to timolol BID and superior to brimonidine TID :
Conclusions
The Combination treatment (brimonidine tartrate 0.2%/ timolol 0.5%) administered BID for 3 months was superior to Timolol (timolol 0.5%) BID and Brimonidine (brimonidine tartrate 0.2%) TID in lowering the elevated IOP of patients with glaucoma or ocular hypertension. The Combination administered BID demonstrated a favourable safety profile that was comparable to Timolol BID and better than Brimonidine TID with regard to the incidence of adverse events and discontinuations due to adverse events.
The invention has been described herein by reference to certain preferred embodiments. However, as obvious variations thereon will become apparent to those skilled in the art, the invention is not to be considered as limited thereto.
[25] There are 25 claims altogether, set out in three different ways commencing at page 17. Claims 1 to 6, inclusive, are directed to a composition containing brimonidine and timolol. Claims 7 to 13 are directed to the packaging of a pharmaceutical agent for reducing intraocular pressure, including brimonidine and timolol (a form of claiming sometimes used in countries that do not permit claims to a medicine per se). Claims 14 to 25 are directed to use of a composition including brimonidine and timolol. The claims are drafted in “dependent” form. That is, later claims incorporate by reference the terms of earlier claims, often in cumulative fashion.
[26] Allergan is asserting claims 2 to 6 inclusive, and 14 to 25 inclusive, of the '764 patent. They are dependent in one way or another on claim 1; therefore, I recite claim 1, as well:
1. An ophthalmic topical pharmaceutical composition for the treatment of glaucoma or ocular hypertension comprising an effective amount of brimonidine and an effective amount of timolol in a pharmaceutically acceptable carrier therefore.
2. A compostion according to Claim 1, wherein the amount of brimonidine is 0.01 to 0.5 percent by weight and the amount of timolol is 0.1 to 1.0 percent by weight.
3. A composition according to Claim 1, wherein the amount of brimonidine is 0.2 percent by weight and the amount of the timolol is 0.5 percent by weight.
4. A composition according to claim 1 further comprising from 0.001% by weight less than 0.01% by weight of benzalkonium chloride.
5. A composition according to claim 2 further comprising from 0.001% by weight to less than 0.01% by weight of benzalkonium chloride.
6. A composition according to claim 3 further comprising from 0.001% by weight to less than 0.01% by weight of benazalkonium chloride.
. . .
14. Topical use of a therapeutically effective amount of a composition according to claim 1 in an affected eye for treating glaucoma.
15. Topical use of a therapeutically effective amount of a composition according to claim 2 in an affected eye for treating glaucoma.
16. Topical use of a therapeutically effective amount of a composition according to claim 3 in an affected eye for treating glaucoma.
17. Topical use of a therapeutically effective amount of a composition according to claim 1 in an affected eye for lowering intraocular pressure.
18. Topical use of a therapeutically effective amount of a composition according to claim 2 in an affected eye for lowering intraocular pressure.
19. Topical use of a therapeutically effective amount of a composition according to claim 3 in an affected eye for lowering intraocular pressure.
20. Topical use of a therapeutically effective amount of a composition according to claim 4 in an affected eye for treating glaucoma.
21. Topical use of a therapeutically effective amount of a composition according to claim 5 in an affected eye for treating glaucoma.
22. Topical use of a therapeutically effective amount of a composition according to claim 6 in an affected eye for treating glaucoma.
23. Topical use of a therapeutically effective amount of a composition according to claim 4 in an affected eye for lowering intraocular pressure.
24. Topical use of a therapeutically effective amount of a composition according to claim 5 in an affected eye for lowering intraocular pressure.
25. Topical use of a therapeutically effective amount of a composition according to claim 6 in an affected eye for lowering intraocular pressure.
[27] Allergan, in its written argument at paragraph 19, puts forward claim 22 as important and representative. It depends upon claim 6, which depends upon claim 3, which depends upon claim 1. I recite these claims in descending order.
Claim 22 – Topical use of a therapeutically effective amount of a composition according to claim 6 in an affected eye for treating glaucoma.
Claim 6 – A composition according to claim 3 further comprising from 0.001% by weight to less than 0.01% by weight of benzalkonium chloride.
Claim 3 – A composition according to Claim 1, wherein the amount of brimonidine is 0.2 percent by weight and the amount of the timolol is 0.5 percent by weight.
Claim 1 – An ophthalmic topical pharmaceutical composition for the treatment of glaucoma or ocular hypertension comprising an effective amount of brimonidine and an effective amount of timolol in a pharmaceutically acceptable carrier therefore.
[28] Taking into account all of the “dependencies” relating to claim 22, that claim can be rewritten as follows:
22. Topical use of a therapeutically effective amount of an ophthalmic pharmaceutical composition for the treatment of glaucoma or ocular hypertension wherein the amount of brimonidine is 0.2 percent by weight and the amount of timolol is, 0.5 percent by weight, and from 0.001% by weight to less than 0.01% by weight of benzalkonium chloride.
THE EVIDENCE
[29] As is usual in these types of applications, the evidence took the form of affidavits and transcripts of cross-examinations. No witness was examined before the Court. Thus, the Court is unable to make a truly proper assessment as to credibility of any witness, nor to weigh properly the competing opinions of the experts. However, having reviewed the transcripts of the cross-examination of Allegan’s expert witness Dr. Fechtner, I find him to be evasive and less than forthright on many occasions. I will treat his evidence with great caution.
[30] The issues in this proceeding have been much reduced to those respecting invalidity of certain claims of the ‘764 patent. At a pre-trial conference, I invited the parties to advise the Court as to what evidence on the record no longer needs to be considered and possibly be removed from the record. The parties advised jointly by a letter from Allergan’s Counsel dated May 9, 2012:
We write further to the case conference held on May 8, 2012 in respect of T-1560-10. We write with the consent of Apotex Inc. (“Apotex”).
The parties are in agreement that the following evidence need not be reviewed by the Court in advance of the hearing:
Applicants’ Record
§ The affidavits of Dr. Kevin Parkinson dated March 28 and May 31, 2011
§ Paras. 5-8 and Exhibits “C” to “F” of the affidavit of Sonia Atwell dated May 31, 2011
Respondent Apotex’ Record
§ The affidavit of Biserka Horvat dated March 31, 2011
§ The cross-examination transcript of Dr. Kevin Parkinson dated September 19, 2011
§ Paras. 81, 83-88, 91-292 and Exhibits 3-30 to the affidavit of Dr. Harry Quigley dated March 31, 2011
The parties are not asking the Court to strike any portions of the record.
[31] At the hearing, Counsel for each of the parties agreed that the above-referenced material could be removed from the record as it was not referred to in argument. These portions were to be removed following the hearing. None of it was referred to in argument.
[32] The Applicants Allergan filed the following evidence which remains for consideration:
1. Affidavit of Gary J. Beck, one of the named inventors in the '764 patent. His evidence is factual. He is the Senior Director, Global Project Management, Analysis, at Allergan, Inc. in California. His evidence reviews the developments that led to the '764 patent, provides revenues generated by the sale of the COMBIGAN product and provides cost figures relating to the development of that product.
He was cross-examined and a transcript of that cross-examination has been filed in evidence.
2. Affidavit of Sonia Atwell, a law clerk in the offices of the Applicants’ solicitors. Her evidence is factual; it serves to place several documents in the record.
She was not cross-examined.
3. Affidavit of Dr. Robert Fechtner, a Professor of Ophthalmology and Director of the Glaucoma Division, Glaucoma Diagnostic Laboratory and Clinical Research Development at the Institute of Ophthalmology and Visual Science at New Jersey Medical School of the University of New Jersey. His evidence is filed as expert evidence. His expertise lies in the fields of study, research and teaching respecting the treatment of glaucoma and other ocular conditions. He is not a formulator of drugs used for that purpose although he has worked with such formulators. During his cross-examination he expressly stated that he was not an expert in formulation (e.g. Q’s 24-26). He testified in respect of the issues of anticipation and obviousness of the '764 patent. He rebuts some of the evidence given by Apotex’s experts.
He was cross-examined and a transcript of that cross-examination has been filed in evidence. I have already stated my reservations as to his evidence.
4. Affidavit of Jim Tierney, the Business Unit Director, Eye Care for Allergan Inc. His evidence is factual. He testified as to prescription data for bimatoprost and travoprost in Canada.
He was not cross-examined.
[33] The Respondent Apotex filed the following evidence which remains for consideration:
1. Affidavit of Salman Hoda, a Marketing Forecast Analyst at Apotex. He is a factual witness. He provided marketing data, derived from a marketing survey data source, as to sales of brimatoprost, timolol, dorzolamine, dorzolamine-timolol and brimonidine-timolol products in Canada.
He was cross-examined and a transcript of that cross-examination was filed in evidence.
2. Affidavit of Harry A. Quigley, A. Edward Maumenee Professor of Ophthalmology at the Wilmer Eye Institute at Johns Hopkins University, Baltimore, Maryland. His evidence was filed as expert evidence. His expertise lies in the field of study, research and teaching in respect of glaucoma and other ocular conditions. He testified as to the issues of obviousness and anticipation of the '764 patent.
He was cross-examined, and a transcript of his cross-examination was filed in evidence.
3. Affidavit of Uday B. Kompella, a Professor in the Department of Pharmaceutical Sciences at the University of Colorado Denver. His evidence was filed as expert evidence. His expertise lies in the field of formulation and delivery of ocular drugs. He testified as to obviousness of the '764 patent. He also responded to the Beck affidavit.
He was cross-examined and a transcript of his cross-examination was filed in evidence.
4. Affidavit of Aidan Hollis, a Professor of Economics at the University of Calgary. His evidence was filed as expert evidence. He testified in respect of COMBIGAN sales and sales of other ophthalmic products in Canada.
He was cross-examined and a transcript of that cross-examination was filed in evidence.
PREVIOUS FEDERAL COURT DECISION RESPECTING THE '764 PATENT
[34] There has been previous litigation in the Federal Court respecting the '764 patent in the context of the NOC Regulations. In a decision released November 17, 2011, cited as Allergan Inc, et al v Canada (Minister of Health) and Sandoz Canada Inc, 2011 FC 1316, Justice Crampton (as he then was – I will refer to him as Crampton J in these Reasons.) determined that allegations made by a generic, Sandoz Canada Inc, inter alia, that the '764 patent was invalid for obviousness, were not justified. He wrote at paragraph 127 of that decision:
127 Allergan has met its burden of establishing, on a balance of probabilities, that Sandoz's allegation that the '764 Patent is invalid on the ground of obviousness is not justified. For the reasons summarized in paragraph 117 above, this would remain true even if the inventive concept of the claims of the '764 Patent did not include the uncontested surprising improvement in safety, the elimination of the afternoon reduction of effectiveness and the reduction in daily load of BAK, relative to concomitant treatment of brimonidine and timolol. These additional aspects of the inventive concept simply serve to further strengthen that the invention claimed by the '764 Patent was not obvious.
[35] He was not asked to deal with the issue of anticipation of the ‘764 patent.
[36] I am advised that this decision is a final decision. I will refer to this decision as Sandoz.
PREVIOUS UNITED STATES DECISION
[37] The United States District Court, Eastern District of Texas, Marshall Division, released a decision dated August 22, 2011 in a case between Allergan, Inc v Sandoz Inc, cited as 2011 WL 3809882 (E.D.Tex.). I am advised that this decision is under appeal with an oral hearing expected in the fall of this year, 2012.
[38] This decision dealt with four United States patents which emerged from the same priority application as that claimed in the '764 patent; namely, a filing in the United States Patent Office on April 19, 2002 as number 10/126,790. The District Court determined that these patents were not invalid.
[39] This litigation was brought under the provisions of the United States Hatch-Waxman Act, [Public Law 98-417] (formally known as the Drug Price Competition and Patent Term Restoration Act), of which our NOC Regulations are an imperfect copy.
ISSUES
[40] The basic issue before me is whether Allergan has discharged its burden of demonstrating that Apotex’s allegation of invalidity of the '764 patent are not justified; thus the Court must determine whether an order for prohibition should issue.
[41] In determining this matter, there are several discrete issues:
1. Who bears the burden?
2. Effect of the previous Federal Court decision.
3. Effect of the United States Federal Court decision
4. Who is the person skilled in the art?
5. .Construction of the claims
6. Are the asserted claims of the '764 patent anticipated?
7. Are the asserted claims of the '764 patent obvious?
ISSUE #1: Who bears the burden?
[42] As to the allegations of invalidity, the Patent Act, RSC 1985, P-4, section 43(2) affords a presumption of validity; however, once a second person, here Apotex, puts in some evidence as to invalidity, the Court must determine the matter on the usual civil burden; namely, balance of probabilities. I repeat what I wrote in GlaxoSmithKline Inc v Pharmascience Inc, 2011 FC 239 at paras 43 and 44:
43 O'Reilly J of this Court has summarized the question of burden of proof where the issue is invalidity in Pfizer Canada Inc. v. Apotex Inc., 2007 FC 26, 59 CPR (4th) 183 (aff'd 2007 FCA 195, leave to appeal refused [2007] SCCA No. 371) at paragraphs 9 and 12:
9 In my view, the burden on a respondent under the Regulations is an "evidential burden" -- a burden merely to adduce evidence of invalidity. Once it has discharged this burden, the presumption of validity dissolves and the Court must then determine whether the applicant has discharged its legal burden of proof. I believe this is what is meant in those cases where the Court has stated that the respondent must put its allegations "into play". It must present sufficient evidence to give its allegations of invalidity an air of reality.
...
12 To summarize, Pfizer bears the legal burden of proving on a balance of probabilities that Apotex's allegations of invalidity are unjustified. Apotex merely has an evidentiary burden to put its case "into play" by presenting sufficient evidence to give its allegations of invalidity an air of reality. If it meets that burden, then it has rebutted the presumption of validity. I must then determine whether Pfizer has established that Apotex's allegations of invalidity are unjustified. If Apotex does not meet its evidential burden, then Pfizer can simply rely on the presumption of validity to obtain its prohibition order.
44 In Pfizer Canada Inc. v. Canada (Minister of Health), 2008 FC 11, 69 C.P.R. (4th) 191, I said in respect of the same thing at paragraph 32:
32 I do not view the reasoning of the two panels of the Federal Court of Appeal to be in substantial disagreement. Justice Mosley of this Court reconciled these decisions in his Reasons in Pfizer Canada Inc. v. Apotex Inc., [2007] F.C.J. No. 1271, 2007 FC 971 at paragraphs 44 to 51. What is required, when issues of validity of a patent are raised:
1. The second person, in its Notice of Allegation may raise one or more grounds for alleging invalidity;
2. The first person may in its Notice of Application filed with the Court join issue on any one or more of those grounds;
3. The second person may lead evidence in the Court proceeding to support the grounds upon which issue has been joined;
4. The first person may, at its peril, rely simply upon or, more prudently, adduce its own evidence as to the grounds of invalidity put in issue.
5. The Court will weigh the evidence; if the first person relies only on the presumption, the Court will the presumption of validity afforded by the Patent Act nonetheless weigh the strength of the evidence led by the second person. If that evidence is weak or irrelevant the presumption will prevail. If both parties lead evidence, the Court will weigh all the evidence and determine the matter on the usual civil balance.
6. If the evidence weighed in step 5 is evenly balanced (a rare event), the Applicant (first person) will have failed to prove that the allegation of invalidity is not justified and will not be entitled to the Order of prohibition that it seeks.
ISSUE #2: The effect of the earlier Federal Court decision
a) The decision
[43] The Federal Court in Allergan Inc et al v Canada (Minister of Health) and Sandoz Canada Inc, 2011 FC 1316, (Sandoz) dealt with proceedings under the NOC Regulations involving two patents; one of them was the same '764 patent, which is the one at issue here; the other was Canadian Patent No. 2,225,626 (the '626 patent), which is not at issue in the present proceedings. The generic in that case was Sandoz Canada Inc., a different generic from Apotex Inc., the generic in these proceedings. Counsel representing the generics is also different in each proceeding.
[44] In the Sandoz proceeding, Allergan led evidence, including that of Mr Gary J. Beck, one of the named inventors, and that of Dr. Robert Fechtner as an expert. Both are witnesses in the present proceeding and I am advised that the affidavits of these two witnesses are in many respects essentially the same as their affidavits in the present proceedings. These persons were cross-examined in each proceeding by different Counsel. I have not been provided with the transcripts of the cross-examinations in the earlier proceeding, but I fully expect that they are different from those in the present proceedings.
[45] Sandoz provided expert evidence from different persons than those offered by Apotex in the present proceedings. Sandoz’s experts were Dr. Henry Jampel and Dr. Ashim Mitra, as set out in Crampton J’s reasons at paragraphs 30 and 31. I do not have copies of their affidavits or transcripts of their cross-examinations. Crampton J., at paragraph 32, expressed serious reservations as to Mitra’s credibility.
[46] Crampton J, in Sandoz, set out the issues at paragraph 33 of his Reasons. The only issue respecting the '764 patent was that of obviousness. At paragraph 35, he sets out the sa