DCT

1:18-cv-00115

Bristol Myers Squibb Co v. DR Reddy's Laboratories Ltd

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Key Events
Complaint

I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:18-cv-00115, D. Del., 01/19/2018
  • Venue Allegations: Defendant Dr. Reddy's Laboratories (DRL), through counsel, agreed 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 the anticoagulant drug Eliquis® (apixaban) constitutes an act of infringement of a patent covering the apixaban compound.
  • Technical Context: The technology lies in the field of small-molecule pharmacology, specifically concerning lactam-containing compounds that function as Factor Xa inhibitors to prevent and treat thromboembolic (blood clotting) disorders.
  • Key Procedural History: The litigation was triggered by DRL's submission of ANDA No. 210082 to the FDA, which seeks approval to market a generic version of Eliquis® before the expiration of the patent-in-suit. This filing included a "Paragraph IV certification," a formal assertion by DRL that the patent-in-suit is invalid, unenforceable, and/or will not be infringed by its proposed generic product, which under the Hatch-Waxman Act, constitutes a technical act of infringement allowing for this suit.

Case Timeline

Date Event
2001-09-21 ’208 Patent Priority Date
2005-11-22 ’208 Patent Issue Date
2017-12-21 DRL sends Eliquis Notice Letter to BMS
2017-12-26 BMS receives Eliquis Notice Letter (no earlier than date)
2018-01-19 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.

The Invention Explained

  • Problem Addressed: The patent addresses the need for novel and effective therapeutic agents for treating thromboembolic disorders, which are caused by the formation of blood clots. Specifically, it sought to develop inhibitors of "activated factor Xa," a critical enzyme in the blood coagulation cascade, with improved pharmacological and pharmacokinetic properties compared to existing treatments (’208 Patent, col. 5:6-21, 5:26-35).
  • The Patented Solution: The patent discloses a family of chemical compounds, defined by a general formula, that are designed to inhibit Factor Xa. The core of the invention is the specific molecular structure of these "lactam-containing compounds," which are asserted to be effective as anticoagulants (’208 Patent, Abstract; col. 5:52-56). The patent provides methods for synthesizing these compounds and formulating them into pharmaceutical compositions.
  • Technical Importance: By targeting Factor Xa, the invention provides a mechanism for intervening in the process of blood clot formation, a key strategy in the prevention and treatment of conditions like deep vein thrombosis, pulmonary embolism, and stroke (’208 Patent, col. 5:6-14).

Key Claims at a Glance

  • The complaint asserts infringement of claims 8, 13, 26-27, and 55-61. Independent claims implicated by this selection include compound claim 1 (via its dependents) and method of treatment claim 55.
  • Claim 8 (Compound Claim): This claim, which depends from claim 1, recites a specific chemical compound:
    • A compound which is "1-(4-methoxyphenyl)-7-oxo-6-[4-(2-oxo-1-piperidinyl)phenyl]-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridin-3-carboxamide" (known as apixaban); or
    • a pharmaceutically acceptable salt form thereof.
  • Claim 55 (Method of Treatment Claim):
    • A method for treating a thromboembolic disorder,
    • comprising: administering to a patient in need thereof a therapeutically effective amount of a compound of claim 13 or a pharmaceutically acceptable salt form thereof.
  • The complaint reserves the right to assert infringement of other claims, including under the doctrine of equivalents (Compl. ¶18-19).

III. The Accused Instrumentality

  • Product Identification: The accused instrumentalities are the 2.5 mg and 5 mg apixaban tablets for which Defendant DRL seeks FDA approval via ANDA No. 210082 (the "DRL ANDA product") (Compl. ¶2).
  • Functionality and Market Context: The DRL ANDA product is a proposed generic version of Plaintiff’s Eliquis® drug. The complaint alleges that by filing its ANDA, DRL has represented to the FDA that its product contains the same active ingredient (apixaban), has the same dosage form and strength, and is bioequivalent to Eliquis® (Compl. ¶13). DRL is seeking approval to market its product for the same indications as Eliquis®, which include the treatment and prevention of various thromboembolic disorders (Compl. ¶10, ¶14).

IV. Analysis of Infringement Allegations

The complaint’s infringement theory is characteristic of Hatch-Waxman litigation: DRL’s filing of an ANDA to obtain approval for a generic drug before the expiration of the patent covering that drug is a statutory act of infringement under 35 U.S.C. § 271(e)(2)(A) (Compl. ¶18). The core allegation is that DRL's proposed product contains apixaban, the specific compound recited in claim 8 of the ’208 patent.

No probative visual evidence provided in complaint.

  • ’208 Patent Infringement Allegations
Claim Element (from Independent Claim 1, as specified in Dependent Claim 8) Alleged Infringing Functionality Complaint Citation Patent Citation
A compound which is 1-(4-methoxyphenyl)-7-oxo-6-[4-(2-oxo-1-piperidinyl)phenyl]-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridin-3-carboxamide or a pharmaceutically acceptable salt form thereof. DRL's ANDA product is alleged to contain apixaban as its active ingredient, which is the compound specified in claim 8. The complaint states DRL has represented to the FDA that its product has the same active ingredient as BMS's Eliquis®, which is apixaban. ¶2, ¶13 col. 62:38-44
  • Identified Points of Contention:
    • Validity Questions: The complaint notes that DRL’s Paragraph IV certification asserts that the ’208 patent is invalid and/or unenforceable (Compl. ¶15). While the specific grounds are not detailed in the complaint, validity challenges in such cases often focus on obviousness over prior art compounds, lack of adequate written description, or enablement. The central dispute will likely concern whether the claimed invention of apixaban was a non-obvious advance over earlier Factor Xa inhibitors known at the time of the invention.
    • Scope Questions: A potential point of contention could be whether the specific form of apixaban in DRL's product (e.g., a particular salt or crystalline polymorph) falls outside the literal scope of the claims. The interpretation of "pharmaceutically acceptable salt form thereof" could become a focus of the infringement analysis.

V. Key Claim Terms for Construction

  • The Term: "a pharmaceutically acceptable salt form thereof"
  • Context and Importance: This term, appearing in the asserted compound claim 8, defines the scope of protection beyond the base apixaban molecule itself. The resolution of what constitutes a "pharmaceutically acceptable salt" is critical, as DRL could potentially design its product around the claim if its chosen salt form is determined to fall outside this definition. Practitioners may focus on this term because small variations in salt forms can be a route to arguing non-infringement in pharmaceutical cases.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The specification provides a broad, exemplary list of potential salts, stating that the compounds "can be used in the form of salts derived from inorganic or organic acids" and lists numerous examples such as hydrochloride, sulfate, citrate, and tartrate (’208 Patent, col. 116:50-67). This suggests an intent to cover a wide variety of conventional salt forms.
    • Evidence for a Narrower Interpretation: The patent defines "pharmaceutically acceptable" as referring to materials that are "not biologically or otherwise undesirable" and can be administered to an individual without causing "undesirable biological effects or interacting in a deleterious manner" (’208 Patent, col. 116:44-48). A party could argue this functional language limits the scope to only those salts proven to be safe and effective, potentially excluding novel or less common salt forms.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges that DRL's future commercial activities would constitute inducement of infringement (Compl. ¶19). This is predicated on DRL seeking approval to market its generic product for the same indications as Eliquis® (Compl. ¶14). The product's labeling and instructions would foreseeably direct medical professionals and patients to use the drug in a manner that infringes the asserted method claims.
  • Willful Infringement: The complaint does not contain an explicit allegation of "willful infringement." However, it alleges facts that establish DRL’s knowledge of the ’208 patent, including its listing in the FDA's Orange Book and DRL’s own notice letter sent to BMS acknowledging the patent (Compl. ¶10, ¶11). These allegations of pre-suit knowledge could be used to support a later claim for enhanced damages should infringement be found.

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

  • A core issue will be one of patent validity: As is common in ANDA litigation where the chemical identity of the generic product is not in dispute, the case will likely hinge on whether DRL can prove by clear and convincing evidence that the asserted claims of the ’208 patent are invalid (e.g., for obviousness over the prior art).
  • A secondary, but potentially dispositive, question will be one of claim scope: Does the specific formulation of apixaban in DRL’s proposed product, particularly its salt or polymorphic form, fall outside the legal construction of the term "a pharmaceutically acceptable salt form thereof" as used in the patent, thereby creating a basis for a non-infringement finding?