Alcon Research, Ltd. v. Apotex, Inc.

ALCON RESEARCH, LTD., ALCON LABORATORIES, INC. ALCON PHARMACEUTICALS, LTD. and KYOWA HAKKO KIRIN CO., LTD. Plaintiffs, v. APOTEX, INC. and APOTEX CORP. Defendants.

1:09-cv-102-RLY-TAB

UNITED STATES DISTRICT COURT SOUTHERN DISTRICT OF INDIANA INDIANAPOLIS DIVISION

SO ORDERED: May 21, 2013

ENTRY ON PLAINTIFFS' MOTION FOR SUMMARY JUDGMENT ON

DEFENDANTS' AFFIRMATIVE DEFENSES AND COUNTERCLAIMS

ALLEGING INEQUITABLE CONDUCT

This case arises out of the Abbreviated New Drug Application ("ANDA") filed by Apotex, Inc., and Apotex Corp. (collectively "Defendants"), with the United States Food and Drug Administration. Apotex seeks approval to manufacture and sell a generic version of Alcon's¹ Pataday™ ophthalmic solution, a prescription eye drop for the treatment of allergic eye disease. Use of the Pataday product, whose active ingredient is olopatadine, is protected by, inter alia, U.S. Patent No. 6,995,186 (the "'186 patent") and United States Patent No. 7,402,609 (the "'609 patent"). After receiving notice ofApotex's ANDA, Alcon filed the present lawsuit² on February 2, 2009, alleging infringement of the '186 and '609 patents.

On September 22, 2010, Apotex filed an Amended Answer, Defenses and Counterclaims. Apotex's Fifth affirmative defense and Count V of its Counterclaim allege that the '186 and '609 patents are unenforceable because the patents were procured through inequitable conduct. Plaintiffs now move for summary judgment with respect to Defendants' inequitable conduct affirmative defenses and counterclaims. For the reasons set forth below, Plaintiffs' motion is DENIED.

I. Factual Background

A. Pataday

Pataday™ is an ophthalmic solution developed and sold by Alcon for the treatment of allergic eye disease. Pataday, which contains olopatadine at a concentration of 0.2%, is protected by the '186 and '609 patents.

Before the development of Pataday, Alcon developed and manufactured Patanol®, a drug remarkably similar to Pataday. Patanol, with an olopatadine concentration of 0.1%, is protected by the '805 patent, noted in footnote 1. The primary difference between these two pharmaceutical drugs is this: Patanol, with a 0.1% concentration of olopatadine, must be administered to the affected eye at least twice a day; Pataday, withtwice the concentration of olopatadine, may be administered just once per day.

Olopatadine at 0.2% is not physically stable, meaning that it will not remain dissolved in solution. Over time, precipitants such as crystals or other particles will form in the solution. (Expert Report of Harry Brittain ¶¶ 32-33). The '186 and '609 patents claim the use of either of two polymers — polyvinylpyrrolidone ("PVP") or polystyrene sulfonic acid ("PSSA") — to enhance the physical stability of low viscosity³ solution compositions containing olopatadine. ('186 patent, col. 16-18; '609 patent, col. 16).

B. The '186 Patent Prosecution History

Attorney Patrick Ryan filed United States Patent Application No. 10/175,106 ("the '106 application"), entitled Olopatadine Formulations for Topical Administration, which led to the '186 and '609 patents. The inventors listed on the application include, inter alia, Dr. Ernesto J. Castillo, Dr. Huixian Zhang, Haresh G. Bhagat, and Joseph Bullock.

As originally filed, the claims in the '106 application did not contain a limitation regarding the viscosity of the claimed compositions. ('186 Patent File History ("PH") at ALPD0005352-55). On June 29, 2004, the PTO Examiner issued an Office Action rejecting all pending claims as either anticipated or obvious over the '805 patent. In particular, the Examiner noted that the '805 patent disclosed "the use of olopatadine in a pharmaceutical composition for the treatment of allergic disorders of the eye," and that "[t]he addition of [PVP] is also taught by the above reference ['805 patent]." (Id. at ALPD0005671).

In response to the Office Action, Ryan met with Bhagat, as well as co-inventors Dr. Castillo and Bullock, to discuss how to respond to the Examiner's determination. (Deposition of Patrick Ryan ("Ryan Dep.") at 168-70). Ryan needed to distinguish the use of PVP on the basis that PVP was able to stabilize olopatadine solutions while maintaining a low viscosity. (Id. at 178-79, 181). To support this argument, the applicants needed data comparing the viscosities of stable olopatadine formulations containing PVP with formulations using other polymers such as polyvinyl alcohol (or "PVA"). Ryan asked Bhagat to generate viscosity data for the three formulations listed in Tables 3 and 4 of the '106 patent application, listed as Formulation H (with HPMC), Formulation I (with Carbopol 974P), and Formulation J (with PVA). (Id. at 183). Bhagat, in turn, requested Dr. Zhang to conduct the testing for the three requested formulations because she was more familiar with viscosity measurements than he. (Deposition of Haresh Bhagat ("Bhagat Dep.") at 143, 145, 149; Deposition of Huixian Zhang ("Zhang Dep.") at 111).

On July 13, 2004, Ryan requested an interview with the Examiner. (PH at ALPD0005684). In the request form, Ryan noted that he planned to offer arguments of "superior results not disclosed or predicted by the prior art." (Id.).

On August 11, 2004, Dr. Zhang conducted the testing as requested by Bhagat for PVA. (See Zhang Laboratory Notebook at ALPD0079674 ("Zhang Lab. Ntbk.")). The results showed three different viscosity data points for Formulation J (polyvinyl alcohol or PVA), which was comprised of 0.2% olopatadine formulation containing 1.8% PVA. (Id.; Bhagat Dep. at 168-69). As specified in the examples of the '106 application, Dr.Zhang measured the viscosity of Formulation J with a Brookfield DV-1+ Viscometer using a CP42 spindle. (Zhang Lab. Ntbk.). The Brookfield viscometer has a variation of experimental data, or error rate, of 5%. (Zhang Dep. at 83-84). Dr. Zhang conducted the test at three different rotation speeds: 12 rpm, 30 rpm, and 60 rpm, and recorded the results in her laboratory notebook.

Formulation J (PVA)

+---------------------------+
¦RPM  ¦Viscosity   ¦Torque  ¦
+-----+------------+--------¦
¦12   ¦2.05 cps    ¦4.0%    ¦
+-----+------------+--------¦
¦30   ¦2.10 cps    ¦10.5%   ¦
+-----+------------+--------¦
¦60   ¦2.00 cps    ¦20%     ¦
+---------------------------+

(Zhang Lab. Ntbk.). Dr. Zhang believed that the 2.10 cps measured at 30 rpm and the 2.00 cps measured at 60 rpm were scientifically valid measurements of the viscosity of Formulation J. (Zhang Dep. at 113-14).

Dr. Zhang noted in her laboratory notebook, without any explanation, that only the 2.10 cps measured at 30 rpm should be reported, marking that data point with an arrow and a note that stated, "Report data." (See Zhang Lab. Ntbk.). At her deposition, Dr. Zhang did not recall why she singled out the 2.10 cps measurement at the time, could not explain why she chose to report the 2.10 cps measurement over the 2.00 cps measurement, or why she did not report both "valid" values. (Zhang Dep. at 116-18).

The day after Dr. Zhang obtained the viscosity data for PVA, she sent an email with an attachment to Bhagat, replying to an email chain that included an email from Ryan to Bhagat discussing the prosecution of the '106 application. (See Pls.' Privilege Log at 26, Entry ALPD0102227-28, at 56, Entry ALPD0107973-74 at 56-57, EntryALPD0107975-76). Bhagat, in turn, forwarded Dr. Zhang's email with the attachment to Ryan. (Id.). Dr. Zhang postponed signing her laboratory notebook until the day after she emailed Bhagat. (See Zhang Lab. Ntbk.). The substance of these emails was ruled to be protected by the attorney-client privilege by order of Magistrate Judge Baker. (See Docket # 182).

Relying on the viscosity data Dr. Zhang collected for PVA, Ryan asked Bhagat to submit a declaration to the PTO. (Ryan Dep. at 179-80). Ryan prepared the initial draft of Bhagat's declaration "after talking with [Bhagat] . . . to understand what he did and what the results were." (Id. at 181). Ryan then provided Bhagat with the 2004 Office Action, which set forth the lack of unexpected results as a reason for the rejection, and the initial draft of his declaration "for him to review and mark up and edit." (Id. at 181, 183). Bhagat added his personal information to the declaration and the technical information regarding olopatadine formulations - including the viscosity data for Formulations H, I, and J — found in paragraphs 6-9 of his declaration. (Bhagat Dep. at 134-35; PH at ALPD0005696-97). Bhagat and Dr. Zhang then exchanged emails. (See Pls.' Privilege Log at 26, Entry ALPD0102227-28, Entry at ALPD0102233-36).

On September 8, 2004, Bhagat reviewed and verified Dr. Zhang's laboratory notebook that contained the viscosity data for Formulation J (PVA). (See Zhang Lab. Ntbk.; Bhagat Dep. at 155, 169). In paragraph 6 of his declaration submitted to the PTO, Bhagat included only the 2.10 cps measurement, and omitted the 2.0 cps measurement and information on the error rate associated with the Brookfield viscometer. (PH at ALPD0005695-97).

On September 9, 2004, Ryan met with the PTO to discuss responding to the 2004 Office Action. According to the Examiner's notes, Ryan agreed to consider "amending the claims to the Jepson format and inserting specific viscosity, and the Office will consider the amendments favorably." (See PH at ALPD0005685). Ryan interpreted the Examiner's remarks as "a nonbinding indication . . . that at least as of that moment, if you provided those things [listed in the Interview Summary], [the PTO] wouldn't have any other basis for rejecting the case and would likely to [sic] give you an allowance." (Ryan Dep. at 166-67). The day after meeting with the Examiner, he and Bhagat exchanged emails. (See Pls.' Privilege Log at 26-27, Entry ALPD0102237-38, at 57, Entry ALPD0107977).

On September 10, 2004, Ryan responded to the June 29, 2004 Office Action by submitting an amendment to the pending claims to specify a viscosity of 1-2 cps. The amendment to...