DCT

1:00-cv-00205

Mylan Pharmaceutical v. Bristol Myers

Log In
Key Events
Amended Complaint

I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:00-cv-00205, N.D. W. Va., 05/18/2001
  • Venue Allegations: Venue is alleged to be proper as the defendant conducts business in the district and a substantial part of the events giving rise to the claim occurred there.
  • Core Dispute: Plaintiff seeks a declaratory judgment that its generic buspirone hydrochloride product does not infringe, and that U.S. Patent No. 6,150,365 is invalid and unenforceable, alleging Defendant improperly listed the patent with the FDA to block generic competition.
  • Technical Context: The lawsuit concerns pharmaceutical methods for treating anxiety, specifically involving the drug buspirone and one of its metabolites.
  • Key Procedural History: The dispute arises from Defendant’s listing of the ’365 patent in the FDA’s “Orange Book” on the day the patent issued. Plaintiff alleges this listing was improper because Defendant made representations to the FDA about the patent’s scope that were directly contrary to representations made to the U.S. Patent and Trademark Office during prosecution. This listing allegedly triggered a stay of FDA approval for Plaintiff’s generic drug, leading to this declaratory judgment action and associated antitrust claims.

Case Timeline

Date Event
1980-01-08 U.S. Patent 4,182,763 (related context) issues
1986-01-01 Bristol-Myers Squibb launches BuSpar®
1999-08-05 Earliest priority date for '365 Patent
2000-11-21 U.S. Patent 6,150,365 issues to Bristol-Myers Squibb
2000-11-21 Bristol-Myers Squibb requests Orange Book listing for '365 Patent
2000-11-22 Expiration of market exclusivity from '763 patent
2000-11-22 Mylan’s planned launch date for its generic buspirone product
2000-11-27 Bristol-Myers Squibb sends letter to Mylan regarding '365 patent
2000-12-04 Mylan Technologies files Paragraph IV certification for 30mg product
2001-03-28 Bristol-Myers Squibb delists '365 Patent from the Orange Book
2001-03-28 Mylan launches its generic buspirone product
2001-05-18 Mylan files Second Amended Complaint

II. Technology and Patent(s)-in-Suit Analysis

U.S. Patent No. 6,150,365 - "Anxiety Method," issued November 21, 2000

The Invention Explained

  • Problem Addressed: The patent’s background states that the anti-anxiety drug buspirone undergoes extensive "first pass metabolism," meaning only a small fraction of the parent drug reaches the bloodstream after oral administration ('365 Patent, col. 1:40-45). The prevailing belief was that buspirone itself was the primary active agent, and treatment strategies focused on maximizing its concentration at the expense of its metabolites ('365 Patent, col. 2:1-6).
  • The Patented Solution: The patent claims the "unexpected discovery" that a specific metabolite of buspirone, identified as 6-hydroxy-buspirone or BMY 28674, is itself a potent anxiolytic agent ('365 Patent, col. 4:50-53). The invention is a method of treating anxiety by administering this active metabolite ('365 Patent, col. 16:26-33). The patent includes a bar graph, Figure 1, purporting to show the dose-dependent anxiolytic effect of the metabolite BMY-28674 in rats (Compl. Ex. 1, '365 Patent, Fig. 1). The specification also describes an "improved method" of administering the parent drug buspirone in a way that favors the metabolic production of BMY 28674, which is contrary to prior teachings that sought to minimize metabolites ('365 Patent, col. 12:5-18).
  • Technical Importance: This discovery proposed a new mechanism of action for buspirone therapy, suggesting that a metabolite, not the parent drug, may be the key driver of the clinical effect, thereby shifting the therapeutic goal from maximizing the parent drug to ensuring sufficient levels of the active metabolite ('365 Patent, col. 9:1-5).

Key Claims at a Glance

  • The complaint asserts non-infringement of the sole independent claim, Claim 1 (Compl. ¶34-35).
  • The essential elements of Claim 1 are:
    • 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 6-hydroxy-8-[4-[4-(2-pyrimidinyl)-piperazinyl]-butyl]-8-azaspiro[4.5]-7,9-dione (the "metabolite")
    • or a pharmaceutically acceptable acid addition salt or hydrate thereof.

III. The Accused Instrumentality

Product Identification

The products at issue are Mylan’s 5, 10, 15, and 30 mg pharmaceutical formulations containing buspirone hydrochloride (Compl. ¶7).

Functionality and Market Context

These products are generic versions of Bristol-Myers Squibb’s branded drug, BuSpar® (Compl. ¶7). The complaint alleges they are intended for the same therapeutic use—the treatment of anxiety. Mylan asserts that it was prepared to launch its product immediately upon the expiration of prior patents and regulatory exclusivities, but was blocked by the Defendant’s listing of the ’365 patent in the FDA Orange Book (Compl. ¶10-11, 22).

IV. Analysis of Infringement Allegations

The complaint seeks a declaratory judgment of non-infringement. Its core theory is that Mylan’s product, which contains the precursor drug buspirone hydrochloride, does not literally meet the limitation of the claim, which requires the administration of the metabolite.

’365 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Non-Infringing Functionality Complaint Citation Patent Citation
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 6-hydroxy-8-[4-[4-(2-pyrimidinyl)-piperazinyl]-butyl]-8-azaspiro[4.5]-7,9-dione or a pharmaceutically acceptable acid addition salt or hydrate thereof. Mylan's buspirone hydrochloride products are alleged not to contain an anxiolytically effective dose of the claimed metabolite, 6-hydroxy-8-[4-[4-(2-pyrimidinyl)-piperazinyl]-butyl]-8-azaspiro[4.5]-7,9-dione. Instead, the products contain the precursor drug, buspirone hydrochloride. ¶34 col. 16:26-33

Identified Points of Contention

  • Scope Questions: The central dispute concerns the scope of the phrase "systemic administration ... of [the metabolite]." A primary question is whether administering a prodrug (buspirone hydrochloride) that the body converts into the claimed metabolite constitutes direct infringement of this claim. The patent specification itself suggests this possibility, stating that systemic administration of the metabolite "may be accomplished by oral administration of a precursor or prodrug form ... e.g. buspirone" ('365 Patent, col. 12:1-6). This creates a potential conflict between the literal claim language and the broader description in the specification.
  • Technical Questions: The complaint raises a significant question regarding prosecution history. It alleges that during prosecution, Bristol distinguished its invention from the prior art use of buspirone, but then represented to the FDA that the patent did cover the use of buspirone (Compl. ¶24, 66-68, 86). This suggests a potential dispute over whether Bristol disclaimed coverage of buspirone administration to secure the patent, which could preclude it from later asserting such a scope in an infringement action.

V. Key Claim Terms for Construction

  • The Term: "systemic administration ... of ... [the metabolite]"
  • Context and Importance: The definition of this phrase is dispositive for the non-infringement analysis. Practitioners may focus on this term because its construction will determine whether the claim is limited to drug products containing the metabolite itself (favoring Mylan's non-infringement argument) or if it extends to administering a precursor drug like buspirone that generates the metabolite in vivo (favoring Bristol's infringement position).
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The detailed description states: "systemic administration of BMY 28674 may be accomplished by oral administration of a precursor or prodrug form of BMY 28674, e.g. buspirone, to mammals" ('365 Patent, col. 12:1-6). This language could be used to argue that the inventors explicitly contemplated that administering the prodrug was a way of performing the claimed method.
    • Evidence for a Narrower Interpretation: The claim language itself recites only the metabolite, not the prodrug buspirone. The abstract similarly focuses only on the metabolite as being "useful in the alleviation of anxiety" ('365 Patent, Abstract). Further, the complaint alleges that to overcome rejections based on prior art use of buspirone, Bristol amended its application to claim only the administration of the metabolite, thereby potentially disclaiming the broader scope (Compl. ¶66-67).

VI. Other Allegations

  • Indirect Infringement: Mylan alleges that it does not and will not induce infringement because the use of its products according to their labels does not fall within the scope of the claim (Compl. ¶36).
  • Willful Infringement: The complaint does not allege willful infringement. Instead, as part of its case for unenforceability and antitrust violations, it makes multiple allegations regarding Bristol's conduct. It claims Bristol committed inequitable conduct by misleading the PTO (Compl. ¶79), engaged in patent misuse by improperly listing the patent in the Orange Book to broaden its scope (Compl. ¶40-41), and committed Walker Process fraud by obtaining the patent through fraudulent representations to the PTO and then attempting to enforce it (Compl. Count 7). The core allegation is that Bristol knowingly made contradictory statements to the PTO and the FDA to improperly delay generic competition (Compl. ¶24, 69-70).

VII. Analyst’s Conclusion: Key Questions for the Case

  • A core issue will be one of claim scope and the prodrug defense: Can the claim term "administration of" the metabolite be construed to cover the administration of its precursor, buspirone, which the body converts into the claimed metabolite in vivo? The answer will depend on whether the broad statements in the patent’s specification can expand the literal language of the claim.
  • A related question will be one of prosecution history estoppel: Did Bristol, in securing the patent, disclaim coverage of methods involving the administration of buspirone itself to overcome prior art? If so, it may be prevented from arguing for that broader scope now, a point central to Mylan’s allegations of contradictory representations.
  • The case also presents a critical question of anticompetitive conduct: Does the evidence show that Bristol knowingly made false representations to the FDA about the scope of the ’365 patent, in direct contradiction to its representations to the PTO, in an unlawful attempt to maintain its monopoly over the buspirone market?