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IN RE BUSPIRONE PATENT LITIGATION

February 14, 2002

IN RE: BUSPIRONE PATENT LITIGATION IN RE: BUSPIRONE ANTITRUST LITIGATION


The opinion of the court was delivered by: Koeltl, Judge

Opinion and Order No. 18

(Motion For Summary Judgment on Patent Infringement Claims)

On August 15, 2001, the Judicial Panel on Multidistrict Litigation consolidated for pre-trial purposes before this Court four patent actions, which had been consolidated under MDL-1410, and twenty-two antitrust actions, which had been consolidated under MDL-1413. All of these cases involve disputes among the various parties over the propriety of the manufacture, use, sale or allegedly anticompetitive conduct related to the use and sale of the drug buspirone*fn1 to treat anxiety. Since that time, the Panel has also transferred twelve tag-along cases to this Court.

Danbury Pharmacal, Inc. and Watson Pharmaceuticals, Inc. (collectively "Watson") and Mylan Pharmaceuticals, Inc., Mylan Laboratories Inc. and Mylan Technologies Inc. (collectively "Mylan") are competitors of Bristol-Myers, who have been seeking to produce or sell generic buspirone tablets for use in accordance with the approved FDA-labeling instructions for Buspar®. To that end, they have each filed Abbreviated New Drug Applications ("ANDAs") with the FDA, seeking approval of their respective products. After obtaining the `365 Patent, however, Bristol-Myers listed it with the FDA in the book entitled the "Approved Drug Products with Therapeutic Equivalence Evaluations," or the "Orange Book," as covering the uses of buspirone in question, thereby triggering an automatic forty-five-day period in which Bristol-Myers could bring patent infringement suits against its generic competitors before they could sue for a declaratory judgment action. Bristol-Myers then filed suits for patent infringement against Mylan and Watson within this forty-five day period, alleging that they infringed the `365 Patent by filing their ANDAs and certifying that their respective products do not violate the `365 Patent. These lawsuits triggered an automatic stay of the FDA's approval of Mylan's and Watson's products for up to the earlier of thirty months or until the relevant patent disputes were decided. See 21 U.S.C. § 355(j)(5)(B)(iii).

Mylan and Watson move pursuant to Rule 56 of the Federal Rules of Civil Procedure for summary judgment on the patent infringement claims based on a finding that these generic competitors' manufacture, promotion and sale of generic buspirone tablets in accordance with the current FDA-approved labeling instructions for Buspar® would not infringe the `365 Patent, or, in the alternative, that the `365 Patent is invalid. Bristol-Myers opposes this motion, or, in the alternative, moves for a Markman hearing in which to produce evidence concerning claim construction. See Markman v. Westview Instruments, Inc, 52 F.3d 967, 979 (Fed. Cir. 1995) (en banc), aff'd, 517 U.S. 370 (1996).*fn2

I.

The standard for granting summary judgment is well established. Summary judgment may not be granted unless "the pleadings, depositions, answers to interrogatories, and admissions on file, together with the affidavits, if any, show that there is no genuine issue as to any material fact and that the moving part[ies are] entitled to a judgment as a matter of law." Fed. R. Civ. P. 56(c); see also Celotex Corp. v. Catrett, 477 U.S. 317 (1986); Gallo v. Prudential Residential Servs. L.P., 22 F.3d 1219, 1223 (2d Cir. 1994); Local 819. Int'l Bhd. of Teamsters, AFL-CIO v. Textile Deliveries, Inc., No. 99 Civ. 1726, 2000 WL 1357494, at *1 (S.D.N.Y. Sep. 20, 2000). "The trial court's task at the summary judgment motion stage of the litigation is carefully limited to discerning whether there are genuine issues of material fact to be tried, not to deciding them. Its duty, in short, is confined at this point to issue-finding; it does not extend to issue resolution." Gallo, 22 F.3d at 1224. The moving parties, Mylan and Watson in this case, bear the initial burden of "informing the district court of the basis for [their] motion" and identifying the matters that they "believe[] demonstrate the absence of a genuine issue of material fact." Celotex, 477 U.S. at 323. The substantive law governing the case will determine those facts that are material and "only disputes over facts that might affect the outcome of the suit under the governing law will properly preclude the entry of summary judgment." Anderson v. Liberty Lobby, Inc., 477 U.S. 242, 248 (1986)

In determining whether summary judgment is appropriate, the Court must resolve all ambiguities and draw all reasonable inferences against the moving parties. See Matsushita Elec. Indus. Co. v. Zenith Radio Corp., 475 U.S. 574, 587 (1986) (citing United States v. Diebold, Inc., 369 U.S. 654, 655 (1962)); see also Gallo, 22 F.3d at 1223. If the moving parties meet their burden, the burden shifts to the nonmoving party, Bristol-Myers in this case, to come forward with "specific facts showing that there is a genuine issue for trial." Fed. R. Civ. P. 56(e). With respect to the issues on which summary judgment is sought, if there is any evidence in the record from any source from which a reasonable inference could be drawn in favor of the nonmoving party, summary judgment is improper. See Chambers v. TRM Copy Ctrs. Corp., 43 F.3d 29, 37 (2d Cir. 1994).

II.

The following facts are either undisputed, are matters of public record or are part of the prosecution history of the `365 Patent.

A.

Buspirone is a drug that can help treat anxiety and the symptoms of anxiety in humans, when used appropriately. See United States Patent No. 6, 150, 365 ("`365 Patent"), at col. 1 (issued Nov. 21, 2000), attached as Ex. 1 to Declaration of Daniel G. Brown dated November 7, 2001 ("Brown Decl."). Buspirone has the chemical formula of 8-[4-(4-(2-pyrimidinyl)-1-piperazinyl]-butyl]-8-azaspiro [4.5] decane-7, 9-dione and exerts these so-called "anxiolytic" effects through human serotonin 1A (5-HT1A) receptors located in neurons throughout the human brain. See id. Once ingested, buspirone is naturally metabolized to produce a number of metabolites in the human body, including one of import to this case, which has the chemical formula of 6-hydroxy-8-[4-[4- (2-pyrimidinyl)-piperazinyl]-butyl]-8 azaspiro [4.5]-7, 9-dione and is commonly referred to as the "6-hydroxy-metabolite" or "BMY 28674" (the "metabolite"). Id. at cols. 1-2.

In 1980, shortly after the discovery of buspirone's anxiolytic potential, Bristol-Myers obtained a patent (the "`763 Patent") that claimed, among other things:

1. A method for the palliative treatment of neurosis in which anxiety symptoms are prominent which comprises administering a non-toxic anxiolytically effective dose of buspirone or a Pharmaceutically acceptable acid addition salt thereof to a neurotic patient.

U.S. Patent No. 4,182,763, at col. 7 (the "`763 Patent") (issued Jan. 8, 1980), attached as Ex. 14 to Brown Decl. The Patent also claimed "[t]he method of claim 1 wherein buspirone hydrochloride is employed, and dosage is by the oral route." Id. In order to sell such a new medication, a pioneer drug company must obtain approval of a New Drug Application ("NDA") from the FDA, and, as part of this process, the pioneer drug company must conduct research establishing that the drug is safe and effective in use. See 21 U.S.C. § 355(b)(1). Bristol-Myers conducted further testing of buspirone and, on September 29, 1986, obtained approval from the Department of Health and Human Services ("DOHHS") for the use and sale of the drug in accordance with a proposed set of labeling instructions reflecting its research. See Letter from DOHH to Bristol-Myers dated September 29, 1986 ("DOHH Approval Letter"), attached as Ex. 2 to Brown Decl. The FDA approval included the approved labeling instructions (the "Final Printed Buspar Labeling"). See id. at 2-13.

In 1984, Congress passed the Hatch-Waxman Amendments, also known as the Drug Price Competition and Patent Term Restoration Act, Pub. L. No. 98-417, 98 Stat. 1585 (1984) (codified as amended at 21 U.S.C. § 355 and 35 U.S.C. § 271(e)), which amended the Federal Food, Drug, and Cosmetic Act ("FDCA") Pub. L. No. 52-675, 52 Stat. 1040 (1938) (codified as amended at 21 U.S.C. § 301-397), to permit the competitors of pioneer drug companies to obtain expedited and cost-efficient approval of generic versions of bioequivalents of drugs that have already obtained prior FDA approval by filing an "Abbreviated New Drug Application" ("ANDA") and relying in part on the safety and effectiveness findings supporting the original NDA for the drug. See Bayer AG v. Elan Pharm. Research Corp., 212 F.3d 1241, 1244 (Fed. Cir. 2000). Under these provisions, pioneer drug companies filing an NDA must include information on any patent that "claims the drug for which the applicant submitted the application or which claims a method of using such drug and with respect to which a claim of patent infringement could reasonably be asserted if a person not licensed by the owner engaged in the manufacture, use, or sale of the drug." 21 U.S.C. § 355(b)(1). If a pioneer drug company obtains a patent that meets these criteria after the NDA has been filed or approved, the company is required to file supplemental information, on the new patent within thirty days of the issuance of the new patent. See 21 U.S.C. § 355(b)(1) & (c)(2). Upon approval of an NDA or receipt of supplemental patent information, the FDA publishes the submitted patent information in a book called the "Approved Drug Products with Therapeutic Equivalence Evaluations," commonly referred to as the "Orange Book." See id. Since its approval in 1986, Bristol-Myers has sold buspirone tablets for the treatment of anxiety under the name Buspar®. (See Brown Decl. Exs. 2, 8, 9, 14.)

Bristol-Myers's original `763 Patent covering buspirone was set to expire at the end of the day on November 21, 2000. In anticipation of this date, a number of Bristol-Myers's competitors began making preparations to manufacture and sell a generic form of buspirone tablets, including filing ANDAs for buspirone. By November 21, 2000, Mylan and Watson had received tentative approval of their ANDAs contingent only on the expiration of the `763 Patent. See Mylan Pharm., Inc. v. Thompson, 139 F. Supp.2d 1, 8 (D.D.C.), rev'd on other grounds, 268 F.3d 1323 (Fed. Cir. 2001); Watson Pharm., Inc. v. Henney, Civ. No. 500-3516, 2001 U.S. Dist. LEXIS 2477, at *3-4 (D. Md. Jan. 18, 2001). Mylan manufactured and was ready to ship its product at 12:00 a.m. on November 22, 2000. See Mylan Pharm, Inc. v. Thompson, 139 F. Supp. 2d at 8.

B.

Before the `763 Patent expired, Bristol-Myers initiated a series of patent applications (the "Applications") that resulted in the `365 Patent. The prosecution history of these Applications is complex, but all of the Applications drew upon the same body of new scientific research. This new research indicated that the 6-hydroxy-metabolite has anxiolytic potential of its own and may even be the primary active agent in the causal mechanisms leading to the reduction of anxiety in successful uses of buspirone. See `365 Patent, at col. 3 ("We have discovered that [the 6-hydroxy-metabolite] . . . is useful as an agent to treat anxiety. . . ."); see generally id. at cols. 3-10. The Applications suggest that the 6-hydroxy-metabolite is "the active metabolite of buspirone." Id. at col. 3.

On August 5, 1999, Bristol-Myers submitted the first of the series of patent applications (the "`842 Application") based on this new research. The `842 Application claimed:

1. A process for ameliorating an undesirable anxiety state in a mammal comprising systemic administration to the mammal of an effective but non-toxic anxiolytic dose of [the 6-hydroxy-metabolite] or a Pharmaceutically acceptable acid addition salt, prodrug, or hydrate thereof.

U.S. Patent Application No. 09/368, 842 (the "`842 Application"), at 12 (filed Aug. 5, 1999) (emphasis added), attached to Brown Decl. at A-7, A-20.*fn3 A "prodrug" of a metabolite is a precursor drug that is converted into the metabolite during the ordinary processes of metabolization. Because buspirone is a prodrug of the 6-hydroxy-metabolite, the `842 Application indisputedly claimed use of buspirone to treat anxiety.

On August 8, 1999, Bristol-Myers also filed a petition to make the `842 Application "special," thus qualifying it for expedited processing under Title VIII, § 708.02 of the Manual of Patent Examining Procedure ("MPEP"). See Petition to Make Special dated August 5, 1999, at 1-2 (filed August 8, 1999), attached to Brown Decl. at A-29, A-29 to A-30. One condition for expedited processing is that an application be limited to a single invention, however, and the Patent Officer found that the `842 Application contained two patentably distinct inventions: one related to the "6-hydroxy-metabolite of Buspirone" and another related to "Buspirone itself." See Patent Office Action on `842 Application, at 2 (emphasis added), attached to Brown Decl. at A-35, A-36. The Patent Officer therefore refused to rule on the petition until Bristol-Myers elected one of the two inventions at issue. See Letter from Bristol-Myers to Patent Office dated November 24, 1999 ("Election Letter"), at 1, attached to Brown Decl. at A-32, A-32.

In response, Bristol-Myers elected to pursue a patent limited to uses of the prodrug buspirone. See Election Letter at 1-2. On December 13, 1999, the Patent Officer rejected the narrowed `842 Application under Sections 102(b) and 103(a) of Title 35 of the United States Code, explaining that (i) "[i]t [was] admitted Drior art . . . that the elected PRODRUG Buspirone is effective for treatment of anxiety disorders and depression"; (ii) the FDA-approved labeling instructions for Buspar®, as revised in May 1998, were "clear evidence of an on sale bar to these claims," which were accordingly "in the public domain" and (iii) use of buspirone to treat anxiety in the way claimed in the `842 Application was obvious from the admitted prior art. Patent Office Action on `842 Application, at 2-3. The Patent Officer explained further that "[t]o discover what happens when the patient swallows his prescribed Buspar pill, (Buspirone forms its 6-hydroxy-metabolite, inherently), is not a patentable discovery. It is inherent." Id. at 4. The Patent Officer also indicated, however, that "[a] divisional application [could still] be filed under 35 U.S.C. § 121 on the non-elected 6-hydroxy metabolite." Id. at 2 (emphasis added)

On January 18, 2000, Bristol-Myers filed a divisional application pursuant to 35 U.S.C. § 121 (the "`161 Divisional Application"). See Data Sheet for U.S. Patent Application No. 09/484, 161, at 1, attached to Brown Decl. at B-6, B-6. This Application was handled by the same Patent Officer. Bristol-Myers defined the claim at issue by formally requesting the Patent Officer to amend the language from claim one of the original `842 Application by deleting the word "prodrug." See Preliminary Amendment dated Jan. 18, 2000, at 1, attached to Brown Decl. at B-7, B-7. Bristol-Myers explained in this filing that "[a]mendment of the claim has been done in order to delete the claimed subject matter contained in the pending parent application [the `842 Application)," and that "[t]his claim amendment elects the non-elected claimed subject matter of the parent application." Id. at 2.

On June 6, 2000, Bristol-Myers filed four more applications, all of which were filed as continuations-in-part (or "CIP Applications") of the `161 Divisional Application and all of which were handled by the same Patent Officer as the prior two Applications. The first two (the "Non-Elected Subject Matter Applications") used the same language as the `161 Divisional Application, claiming, in relevant part, a process for ameliorating anxiety comprising systemic administration of the 6-hydroxy-metabolite, but naming neither "buspirone" nor any "prodrug." See U.S. Patent Application No. 09/588, 221, at 23, attached to Brown Decl. at C-11, C-36; U.S. Patent Application No. 05/588, 222, at 23, attached to Brown Decl. at D-5, D-28. By contrast, the latter two (the "Improved Method Applications") claimed, among other things:

1. An improved process of ameliorating an undesirable anxiety state in a mammal by oral administration of buspirone, the improvement comprising the administration of buspirone, or a pharmaceutically acceptable acid addition salt thereof, in a manner favoring metabolic production of (the 6-hydroxy-metabolite] in the mammal.
7. The improved process of claim 1 wherein the pharmaceutically acceptable salt is buspirone hydrochloride.

See U.S. Patent Application No. 09/588, 223, at 23 (emphasis added), attached to Brown Decl. at E-10, E-33; U.S. Patent Application No. 09/588, 220, at 23 (emphasis added), attached to Brown Decl., at F-11, F-34. These Improved Method Applications also explicitly identified and claimed a number of purportedly non-obvious methods of administering buspirone so as to favor production of the 6-hydroxy-metabolite. See U.S. Patent Application No. 09/588, 223, at 23 (claims 2 to 6); U.S. Patent Application No. 09/588, 220, at 23 (claims 2 to 6). Although the claims in the four patent Applications differed, each used the same specification to describe the invention. On June 9, 2000, shortly after filing these four new Applications, Bristol-Myers abandoned its original `842 Application, see Request for Express Abandonment of `842 Application, attached to Brown Decl. at A-41, A-41, thus leaving five applications pending, including the `161 Divisional Application.

On July 18, 2000, Bristol-Myers filed a Preliminary Communication as part of the `161 Divisional Application, which presented a series of legal arguments concerning the obviousness of the allegedly novel uses of buspirone to favor production of the 6-hydroxy-metabolite that Bristol-Myers's new research recommended and discussed whether any uses had been anticipated by the prior art of buspirone use. See Preliminary Communication dated July 18, 2000, attached to Brown Decl. at B-40. The Preliminary Communication was directed at a defense of the `161 Divisional Application, which claimed the systemic administration of a dose of the 6-hydroxy-metabolite. With regard to obviousness, the Preliminary Communication stated that the "Applicant believes that the information regarding [the 6-hydroxy-metabolite] available to himself and others skilled in the art, not only did not suggest that [the 6-hydroxy-metabolite] be tested as an anxiolytic agent but, in fact, acted to teach away from such use for any hydroxy-buspirone metabolite." Id. at 7. With regard to anticipation, the Preliminary Communication argued that the prior art of buspirone use did not anticipate the effective method of using the drug allegedly identified in Bristol-Myers's new research because the prior art did not result in an effective anxiolytic amount of the 6-hydroxy-metabolite in the bloodstream on every occasion. See id. at 7-14.

The Preliminary Communication also stated that when Bristol-Myers used the term "systemic administration" in the application, Bristol-Myers intended to include the oral administration of the buspirone prodrug form of the 6-hydroxy-metabolite, and that the specification language made this definition clear. See id. at 3. Finally, the Preliminary Communication argued that the deletion of the term "prodrug" from the claim presently before the Examiner did not change the scope of the Applicant's claimed invention, which is a method for treating anxiety by the systemic administration of an effective anxiolytic dose of [the 6-hydroxy-metabolite], irrespective of how this systemically effective dose is accomplished. Id. at 3 (emphasis added). Bristol-Myers did not file the Preliminary Communication in any of the other four pending Applications.

On September 8, 2000, the Patent Officer rejected the two Improved Method Applications on the same grounds that he had rejected the narrowed `842 Application. See Patent Office Action on `220 CIP Application, at 3-5, attached to Brown Decl. at E-51, E-53 to E-55; Patent Office Action on `223 CIP Application, at 3-5, attached to Brown Decl. at F-68, F-70 to F-72. The Patent Officer explained that the claims covered:

processes for ameliorating anxiety comprising the administration of the clinically useful anxiolytic drug, Buspirone, or its salts, known as "Busoar", which has been on sale, and which inherently produces in vivo metabolites, including, inter alia, "BMY 28674", its 6-hydroxy metabolite. Even if there is no apparent motivation to favor production of this metabolite, an on sale public use and sale bar is seen to exist, if the ...

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