DCT

1:19-cv-00055

Bristol Myers Squibb Co v. Unichem Laboratories Ltd

Log In

I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:19-cv-00055, D. Del., 01/09/2019
  • Venue Allegations: Plaintiff alleges that Defendant, through counsel, agreed via email not to contest personal jurisdiction or venue in the District of Delaware.
  • Core Dispute: Plaintiff alleges that Defendant's filing of an Abbreviated New Drug Application (ANDA) to market a generic version of Plaintiff's anticoagulant drug Eliquis® (apixaban) constitutes an act of infringement of a patent covering the compound.
  • Technical Context: The technology relates to small molecule compounds that function as Factor Xa inhibitors, which are a class of anticoagulants used to treat and prevent blood clots.
  • Key Procedural History: This case was initiated under the Hatch-Waxman Act following Defendant’s submission of ANDA No. 210108, which seeks FDA approval to market a generic version of Eliquis®. Defendant provided a Paragraph IV certification asserting that U.S. Patent No. 6,967,208 is invalid, unenforceable, and/or will not be infringed by its proposed generic product. A terminal disclaimer was filed for the patent-in-suit on November 7, 2016.

Case Timeline

Date Event
2001-09-21 ’208 Patent Priority Date
2005-11-22 ’208 Patent Issue Date
2018-12-21 Plaintiff notified of Defendant's ANDA filing
2019-01-09 Complaint Filing Date

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

U.S. Patent No. 6,967,208 - “Lactam-Containing Compounds and Derivatives thereof as Factor Xa Inhibitors”

  • Patent Identification: U.S. Patent No. 6,967,208, “Lactam-Containing Compounds and Derivatives thereof as Factor Xa Inhibitors,” issued November 22, 2005. (Compl. ¶8)

The Invention Explained

  • Problem Addressed: The patent describes a need for effective and safe therapeutic agents for treating thromboembolic disorders, which are caused by the formation of blood clots. The patent notes the desirability of discovering new Factor Xa inhibitors with improved pharmacological characteristics, such as enhanced selectivity against other enzymes, better oral bioavailability, and greater chemical stability. (’208 Patent, col. 5:22-51)
  • The Patented Solution: The invention discloses a family of chemical compounds containing a lactam structure, which are designed to selectively inhibit Factor Xa, an enzyme critical to the blood coagulation cascade. By blocking Factor Xa, these compounds are intended to prevent the formation of thrombin and, consequently, blood clots. (’208 Patent, Abstract; col. 5:52-66)
  • Technical Importance: The development of direct, oral Factor Xa inhibitors represented a significant advance in anticoagulant therapy, offering a potential alternative to older treatments that required frequent monitoring and had numerous drug interactions. (’208 Patent, col. 5:9-21)

Key Claims at a Glance

  • The complaint asserts infringement of claims that depend from independent claims 1 and 52. (Compl. ¶17)
  • Independent Claim 1 is a composition of matter claim directed to a compound of Formula I, "P-M-M₄," or a stereoisomer or pharmaceutically acceptable salt thereof, where P, M, and M₄ represent specific chemical structures and substituent groups defined in a Markush format. (’208 Patent, col. 237:1-67)
  • Independent Claim 52 is a method of use claim with the following essential elements:
    • A method for treating a thromboembolic disorder
    • comprising: administering to a patient in need thereof
    • a therapeutically effective amount of a compound of claim 8 (which is a specific subset of compounds from claim 1) or a pharmaceutically acceptable salt form thereof. (’208 Patent, col. 272:32-37)
  • The complaint asserts infringement of dependent claims 8, 13, 26-27, 52-57, 59-61, 104-108, and 110-112, and reserves the right to assert others. (Compl. ¶17)

III. The Accused Instrumentality

Product Identification

  • The accused instrumentality is the "Unichem ANDA product," identified as 2.5 mg and 5 mg tablets of apixaban, for which Unichem seeks FDA approval via ANDA No. 210108. (Compl. ¶2)

Functionality and Market Context

  • The complaint alleges that Unichem's product contains the same active ingredient (apixaban), has the same dosage form and strength, and is bioequivalent to Plaintiff's Eliquis® product. (Compl. ¶12)
  • The product is intended to be used as a Factor Xa inhibitor for the same medical indications as Eliquis, which include reducing the risk of stroke and systemic embolism, prophylaxis of deep vein thrombosis, and treatment of DVT and pulmonary embolism. (Compl. ¶13; Compl. p. 3)

IV. Analysis of Infringement Allegations

No probative visual evidence provided in complaint. The complaint does not include a claim chart or detailed infringement contentions. The infringement theory is based on 35 U.S.C. § 271(e)(2)(A), which defines the submission of an ANDA seeking approval to market a drug claimed in a patent before its expiration as a technical act of infringement. (Compl. ¶17) The central allegation is that Unichem's product, containing the active ingredient apixaban, will infringe the asserted claims.

The complaint alleges that claim 13, a dependent claim, is infringed. (Compl. ¶17) Claim 13 recites a specific compound, apixaban, by its chemical name. (’208 Patent, col. 266:39-45) The infringement analysis will therefore focus on whether the active ingredient in Unichem's ANDA product is the compound recited in claim 13.

  • Identified Points of Contention:
    • Scope Questions: Unichem's Paragraph IV certification asserts non-infringement. (Compl. ¶14) This raises the question of whether Unichem will argue that its formulation of apixaban falls outside the literal scope of the asserted claims. For instance, disputes could arise over whether Unichem's product is the specific compound of claim 13 or a "pharmaceutically acceptable salt form thereof."
    • Technical Questions: For claims directed to a crystalline form of the compound (e.g., claim 104, which claims a crystalline form of the compound of claim 13), a key technical question will be whether the crystalline form of apixaban in Unichem’s product is the same as that claimed. The complaint does not provide sufficient detail for analysis of this element.

V. Key Claim Terms for Construction

  • The Term: "therapeutically effective amount" (from independent claim 52)
  • Context and Importance: This term is central to the method of treatment claims. Its construction is critical because infringement of these claims depends on whether the dosage specified in Unichem's proposed product label constitutes a "therapeutically effective amount" as defined by the patent. Practitioners may focus on this term because a narrow construction could provide a basis for a non-infringement argument.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The specification defines the term functionally as "an amount of a compound of the present invention that is effective to inhibit Factor Xa." It also provides a broad dosage range, such as "from about 0.01 to 100 mg/kg of body weight per day." (’208 Patent, col. 117:58-61; col. 155:25-27)
    • Evidence for a Narrower Interpretation: The specification also provides more preferred ranges, such as "from about 1.0 to 10 mg/kg," and even more preferable ranges. A party could argue these specific embodiments should limit the scope of the term to these narrower ranges. (’208 Patent, col. 155:28-30)

VI. Other Allegations

  • Indirect Infringement: The complaint alleges that upon approval, Unichem will induce and contribute to infringement by third parties (e.g., doctors and patients). The basis for this allegation is that Unichem is seeking approval to market its generic product for the same indications as Eliquis® and that its product labeling will instruct users to administer the drug in a manner that infringes the asserted method claims. (Compl. ¶13, 18-20)
  • Willful Infringement: The complaint does not use the term "willful," but it lays a foundation for such a claim by alleging Unichem had knowledge of the ’208 patent at least as of its December 21, 2018 notice letter. The prayer for relief requests any "appropriate relief under 35 U.S.C. § 285," which provides for enhanced damages in exceptional cases. (Compl. ¶10; Prayer for Relief ¶5)

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

  • A central issue will be one of factual identity: does the active pharmaceutical ingredient in Unichem's ANDA product meet all the limitations of the asserted compound claims? Given that claim 13 specifically names apixaban, the dispute may focus on subtle structural or salt-form distinctions, or on whether Unichem's product meets the limitations of claims directed to a specific crystalline form.
  • The case will likely hinge on questions of patent validity. Unichem's Paragraph IV certification asserts that the ’208 patent is invalid and/or unenforceable. The ultimate outcome may depend on whether Unichem can prove by clear and convincing evidence that the asserted claims are invalid on grounds such as obviousness or anticipation over the prior art.
  • For the method of use claims, a key question will be one of induced infringement: assuming the patent is valid and the compound infringes, will Unichem's proposed product label contain instructions that actively encourage or instruct medical professionals and patients to use the drug in a manner that directly infringes the patented methods of treatment?