DCT

1:24-cv-00587

Acerta Pharma BV v. Cipla Ltd

Log In

I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:24-cv-00587, D. Del., 05/16/2024
  • Venue Allegations: Venue is alleged to be proper in the District of Delaware because Defendant Cipla USA, Inc. is a Delaware corporation and thus "resides" in the district, and because Defendant Cipla Limited is a foreign corporation subject to personal jurisdiction in the district.
  • Core Dispute: Plaintiffs allege that Defendants’ submission of an Abbreviated New Drug Application (ANDA) to the FDA, seeking to market a generic version of the cancer drug CALQUENCE®, infringes two patents covering the drug's method of use and its active ingredient's specific crystal form.
  • Technical Context: The technology relates to acalabrutinib, a Bruton's tyrosine kinase (BTK) inhibitor used as a targeted therapy for certain B-cell malignancies, such as chronic lymphocytic leukemia and mantle cell lymphoma.
  • Key Procedural History: The litigation was triggered by Defendants' submission of ANDA No. 219228 with a Paragraph IV certification, asserting that the patents-in-suit are invalid and/or will not be infringed. The complaint alleges that in their notice letter, Defendants did not contest infringement of the asserted claims on any basis other than alleged invalidity.

Case Timeline

Date Event
2014-01-21 ’083 Patent Priority Date
2015-07-03 ’829 Patent Priority Date
2019-04-30 ’083 Patent Issue Date
2021-07-13 ’829 Patent Issue Date
2024-04-24 Cipla's Tablet Notice Letter Date
2024-05-16 Complaint Filing Date

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

U.S. Patent No. 10,272,083 - "Methods of Treating Chronic Lymphocytic Leukemia and Small Lymphocytic Leukemia Using a BTK Inhibitor"

The Invention Explained

  • Problem Addressed: The patent's background section notes that while standard chemotherapies for chronic lymphocytic leukemia (CLL) and small lymphocytic leukemia (SLL) exist, they are often associated with toxicities and immunosuppression (’083 Patent, col. 1:44-48). It further explains that existing therapies may not successfully eradicate malignant B cells within the protective microenvironment of bone marrow and lymph nodes (’083 Patent, col. 2:2-6).
  • The Patented Solution: The patent discloses a method of treating these specific cancers by orally administering a particular Bruton's tyrosine kinase (BTK) inhibitor, identified as the compound of Formula (II) (acalabrutinib) (’083 Patent, col. 2:10-18). By targeting the BTK protein, which is crucial for B cell signaling, the invention provides a specific mechanism for treating these B cell malignancies.
  • Technical Importance: This technology represents a targeted therapy approach that interferes with specific signaling pathways in cancer cells, offering a potential alternative to broader, more traditional chemotherapies (’083 Patent, col. 1:24-33).

Key Claims at a Glance

  • The complaint asserts independent claim 1 and dependent claim 8 (’083 Patent, col. 33:1-34:12; Compl. ¶32).
  • The essential elements of independent claim 1 are:
    • A method of treating chronic lymphocytic leukemia (CLL) or small lymphocytic leukemia (SLL) in a human subject suffering therefrom.
    • The method comprises the step of orally administering to the human subject a dose of 100 mg twice daily of a Bruton's tyrosine kinase (BTK) inhibitor.
    • The BTK inhibitor is a compound of Formula (II), (S)-4-(8-amino-3-(1-(but-2-ynoyl)pyrrolidin-2-yl)imidazo[1,5-a]pyrazin-1-yl)-N-(pyridin-2-yl)benzamide, or a pharmaceutically acceptable salt, solvate, or hydrate thereof.

U.S. Patent No. 11,059,829 - "Crystal Forms of (S)-4-(8-amino-3-(1-but-2-ynoylpyrrolidin-2-yl)imidazo[1,5-a]pyrazin-1-yl)-N-(pyridin-2-yl)benzamide Maleate"

The Invention Explained

  • Problem Addressed: The patent addresses the common pharmaceutical challenge that different solid-state forms of a drug's active ingredient (e.g., polymorphs, solvates, salts) can have varying physical properties such as solubility, stability, and bioavailability. Identifying and characterizing a stable, reproducible crystalline form is critical for drug development and manufacturing.
  • The Patented Solution: The invention describes and claims specific crystalline forms of acalabrutinib maleate (’829 Patent, Abstract). These forms are precisely defined by their characteristic peaks in an X-ray powder diffraction (XRPD) pattern, providing a consistent and characterizable solid material for use in a pharmaceutical composition (’829 Patent, col. 2:15-24).
  • Technical Importance: A well-defined crystalline form is essential for ensuring lot-to-lot consistency in drug manufacturing, as well as predictable stability and dissolution profiles for an orally administered drug product.

Key Claims at a Glance

  • The complaint asserts independent claim 1 (’829 Patent, col. 128:27-35; Compl. ¶50).
  • The essential elements of independent claim 1 are:
    • A crystalline form of (S)-4-(8-amino-3-(1-(but-2-ynoyl)pyrrolidin-2-yl)imidazo[1,5-a]pyrazin-1-yl)-N-(pyridin-2-yl)benzamide maleate.
    • The crystalline form is characterized by a reflection X-ray powder diffraction pattern comprising peaks at 5.5, 9.8, 10.2, 11.6, and 19.3°2θ±0.2° 2θ.

III. The Accused Instrumentality

Product Identification

Defendants' proposed generic version of CALQUENCE®, described in ANDA No. 219228 as an "acalabrutinib maleate tablet, 100 mg base equivalent" (Compl. ¶¶1, 27).

Functionality and Market Context

The accused product is a generic oral tablet containing acalabrutinib maleate as its active ingredient (Compl. ¶27). It is intended for the same therapeutic uses as CALQUENCE®, namely the treatment of adult patients with certain types of lymphoma and leukemia (Compl. ¶¶23-24). The complaint alleges that upon approval, Defendants will manufacture, market, and sell this generic product in the United States (Compl. ¶10). A chemical structure diagram of the acalabrutinib compound is provided in the complaint (Compl. p. 8).

IV. Analysis of Infringement Allegations

U.S. Patent No. 10,272,083 Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method of treating chronic lymphocytic leukemia (CLL) or small lymphocytic leukemia (SLL) in a human subject suffering therefrom Defendants' proposed product labeling will direct and instruct physicians and patients to use the generic acalabrutinib tablets for the treatment of CLL and SLL. ¶38 col. 2:10-12
comprising the step of orally administering, to the human subject, a dose of 100 mg twice daily of a Bruton's tyrosine kinase (BTK) inhibitor The accused product is a 100 mg oral tablet, and its proposed labeling will allegedly direct a twice-daily dosing regimen. ¶¶27, 38 col. 2:35-37
wherein the BTK inhibitor is a compound of Formula (II)... or a pharmaceutically acceptable salt, solvate, or hydrate thereof. The active ingredient of the accused product is identified as "acalabrutinib maleate," which is a salt form of the compound of Formula (II). ¶¶27, 32 col. 2:13-18

Identified Points of Contention

  • Scope Questions: A potential question for the court is whether Defendants' proposed product label will inevitably direct or encourage medical professionals and patients to perform every step of the claimed method. Infringement will depend on the specific instructions and indications included in the FDA-approved label.
  • Technical Questions: Given that the complaint alleges Defendants' notice letter contested only validity and not infringement (Compl. ¶35), the primary dispute may shift away from technical mismatches in infringement toward Defendants' invalidity contentions, which are not detailed in the complaint.

U.S. Patent No. 11,059,829 Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A crystalline form of (S)-4-(8-amino-3-(1-(but-2-ynoyl)pyrrolidin-2-yl)imidazo[1,5-a]pyrazin-1-yl)-N-(pyridin-2-yl)benzamide maleate, The accused product is alleged to be, or contain, this specific crystalline form of acalabrutinib maleate. ¶54 col. 128:27-31
characterized by a reflection X-ray powder diffraction pattern comprising peaks at 5.5, 9.8, 10.2, 11.6, and 19.3°2θ±0.2° 2θ. The complaint alleges that the accused product will infringe this claim but does not provide specific evidence, such as XRPD data, to demonstrate that the crystalline form in the accused product exhibits these characteristic peaks. ¶54 col. 128:32-35

Identified Points of Contention

  • Scope Questions: The case may involve questions about the scope of "comprising" in the context of an XRPD pattern. For instance, arguments could arise if the accused product's pattern includes the claimed peaks but also contains additional, unlisted peaks.
  • Technical Questions: The central issue for the ’829 Patent is evidentiary: what is the actual crystal structure of the acalabrutinib maleate in Defendants' ANDA product? The complaint does not provide the technical data (e.g., an XRPD analysis of Defendants' product) required to substantiate the allegation that it meets the specific peak limitations of claim 1.

V. Key Claim Terms for Construction

For the ’083 Patent

  • The Term: "a dose of 100 mg twice daily"
  • Context and Importance: This term defines the specific treatment regimen. For induced infringement, Plaintiffs must show that the accused product's label will instruct or encourage users to follow this exact regimen. Practitioners may focus on this term to determine if the proposed label allows for non-infringing uses (e.g., different dosages or frequencies) that are substantial enough to defeat the inducement claim.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The complaint does not provide a basis for analysis of this element.
    • Evidence for a Narrower Interpretation: The patent repeatedly specifies the "100 mg" dose administered "twice daily" as a core aspect of the method, suggesting it is a specific and essential limitation rather than an exemplary dosage (’083 Patent, Abstract; col. 2:35-37).

For the ’829 Patent

  • The Term: "characterized by a reflection X-ray powder diffraction pattern"
  • Context and Importance: This phrase links the claimed crystalline form to a specific, measurable physical property. Practitioners may focus on this term because the infringement analysis will hinge entirely on a factual comparison between the XRPD pattern data presented in the patent and the pattern exhibited by the accused product. The dispute is less about defining the term and more about applying it to the facts.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The patent uses the word "comprising" before listing the peaks, which in patent law is typically open-ended and could be construed to mean the pattern must include these peaks but could also include others.
    • Evidence for a Narrower Interpretation: The patent specification provides specific examples and figures (e.g., ’829 Patent, FIG. 1, FIG. 12) showing XRPD patterns for particular forms, which could be used to argue that the claimed pattern should closely resemble these disclosed examples to fall within the claim's scope.

VI. Other Allegations

Indirect Infringement

The complaint alleges both induced and contributory infringement for both patents. For the ’083 method patent, inducement is based on the allegation that Defendants' proposed labeling will instruct and encourage medical professionals and patients to perform the claimed treatment method (Compl. ¶39). For the ’829 composition patent, inducement and contribution are based on the allegation that Defendants will sell a product containing the patented crystal form with knowledge and intent that it be used (Compl. ¶¶57-58).

Willful Infringement

The complaint alleges that Defendants have acted with "full knowledge" of the patents-in-suit, suggesting a basis for willful infringement (Compl. ¶¶42, 60). This knowledge is evidenced by Defendants' submission of the Paragraph IV certification, which required them to identify and address Plaintiffs' patents.

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

  • A central evidentiary question will be one of physical identity: for the ’829 patent, can Plaintiffs prove through discovery and testing that the acalabrutinib maleate in Defendants' proposed generic product possesses the specific crystalline structure defined by the X-ray powder diffraction peaks recited in claim 1?
  • A key legal issue will be one of patent validity: as the complaint alleges Defendants' notice letter focused its challenge on invalidity rather than non-infringement, the case will likely turn on whether Defendants can prove by clear and convincing evidence that the asserted claims of the ’083 and ’829 patents are invalid under U.S. patent law.
  • A core infringement question for the ’083 patent will be one of inducement: will the final, FDA-approved label for Defendants' generic product contain instructions and indications that necessarily lead a substantial number of users to perform the patented method of treatment, or will it allow for substantial non-infringing uses?