DCT

3:24-cv-07346

AstraZeneca Pharma LP v. Cipla Ltd

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 3:24-cv-07346, D.N.J., 06/28/2024
  • Venue Allegations: Venue is asserted in the District of New Jersey based on Defendant Cipla USA, Inc. maintaining its principal place of business in the District, and on the basis that 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 for a generic version of the cancer drug LYNPARZA® (olaparib) constitutes an act of infringement of five patents related to methods of using and formulating the drug.
  • Technical Context: The dispute concerns olaparib, an inhibitor of poly (ADP-ribose) polymerase (PARP), a class of drugs that has become a significant treatment modality for cancers with specific DNA repair deficiencies.
  • Key Procedural History: The complaint notes that U.S. Patent Nos. 11,970,530 and 11,975,001 issued in April and May of 2024, respectively, shortly before the filing of this lawsuit. Cipla's infringement challenge is based on a Paragraph IV Certification notice letter dated May 21, 2024, which alleged that three of the patents-in-suit were invalid, unenforceable, and/or not infringed.

Case Timeline

Date Event
2003-07-25 U.S. Patent No. 8,859,562 Priority Date
2008-10-07 U.S. Patent Nos. 8,475,842, 11,633,396 & 11,975,001 Priority Date
2013-07-02 U.S. Patent No. 8,475,842 Issued
2014-10-14 U.S. Patent No. 8,859,562 Issued
2020-08-13 U.S. Patent No. 11,970,530 Priority Date
2023-04-25 U.S. Patent No. 11,633,396 Issued
2024-04-30 U.S. Patent No. 11,970,530 Issued
2024-05-07 U.S. Patent No. 11,975,001 Issued
2024-05-21 Date of Cipla's Notice Letter to Plaintiffs
2024-06-28 Complaint Filed

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

U.S. Patent No. 8,859,562 - Use of an Agent which Inhibits PARP Activity for the Manufacture of a Medicament for the Treatment of Cancer

Issued October 14, 2014

The Invention Explained

  • Problem Addressed: The patent addresses the need for cancer treatments that are more effective and selective in killing cancer cells without the severe side effects associated with traditional chemotherapy and radiotherapy, which harm healthy cells as well (’562 Patent, col. 2:1-7).
  • The Patented Solution: The invention is a method of treatment based on the discovery that cancer cells deficient in the Homologous Recombination (HR) DNA repair pathway are particularly sensitive to inhibitors of a different enzyme, poly(ADP-ribose) polymerase (PARP) (’562 Patent, col. 2:8-14). By administering a PARP inhibitor, the method selectively targets and kills cancer cells with HR defects (such as those with BRCA1 or BRCA2 mutations) while having a reduced effect on healthy cells with functional HR pathways (’562 Patent, col. 1:44-53).
  • Technical Importance: This approach, often called "synthetic lethality," represented a significant advance in personalized cancer therapy by exploiting a specific genetic vulnerability within tumor cells, leading to targeted treatments with potentially higher efficacy and lower toxicity.

Key Claims at a Glance

  • The complaint asserts independent claim 1 (Compl. ¶42).
  • Claim 1 requires:
    • A method of treatment of cancer in a patient,
    • wherein the cancer cells of the patient are defective in Homologous Recombination (HR),
    • comprising administering to the patient a therapeutically effective amount of an inhibitor of poly(ADP-ribose) polymerase (PARP) activity.
  • The complaint reserves the right to assert additional claims (Compl. ¶40).

U.S. Patent No. 8,475,842 - Immediate Release Pharmaceutical Formulation of 4-[3-(4-Cyclopropanecarbonyl-Piperazine-1-Carbonyl)-4-Fluoro-Benzyl]-2H-Phthalazin-1-One

Issued July 2, 2013

The Invention Explained

  • Problem Addressed: The patent identifies the technical challenge that the active drug, olaparib, is poorly soluble and moderately permeable, which can lead to low and inconsistent bioavailability when administered orally in a conventional immediate-release tablet form (’842 Patent, col. 2:28-56). This poor bioavailability can require larger doses and more frequent administration, creating patient compliance issues and higher manufacturing costs (’842 Patent, col. 3:9-20).
  • The Patented Solution: The invention is a specific pharmaceutical formulation that improves the bioavailability of olaparib. It uses a "solid dispersion" where the drug is combined with a particular matrix polymer, copovidone, which exhibits low moisture absorption (hygroscopicity) and a high softening temperature (’842 Patent, col. 4:11-23). This formulation is designed to keep the drug in a more soluble, amorphous state, enhancing its dissolution and absorption in the gastrointestinal tract (’842 Patent, col. 10:26-44).
  • Technical Importance: Developing a stable, solid oral dosage form with improved bioavailability for a poorly soluble drug is a critical step in making a therapy commercially viable and effective for patient use.

Key Claims at a Glance

  • The complaint asserts independent claim 1 (Compl. ¶57).
  • Claim 1 requires:
    • An immediate-release pharmaceutical composition
    • in the form of a solid dispersion
    • comprising 4-[3-(4-cyclopropanecarbonyl-piperazine-1-carbonyl)-4-fluoro-benzyl]-2H-phthalazin-1-one [olaparib]; and copovidone;
    • wherein the total concentration of [olaparib] in the composition is in the range of from 10% by weight to 40% by weight; and
    • wherein the weight ratio of [olaparib] to copovidone is in the range of from 1:1 to 1:9.
  • The complaint reserves the right to assert additional claims (Compl. ¶55).

U.S. Patent No. 11,633,396 - Immediate Release Pharmaceutical Formulation of 4-[3-(4-Cyclopropanecarbonyl-Piperazine-1-Carbonyl)-4-Fluoro-Benzyl]-2H-Phthalazin-1-One

Issued April 25, 2023

  • Technology Synopsis: This patent, a continuation of the family that includes the ’842 Patent, is also directed to immediate-release pharmaceutical compositions of olaparib. It claims a formulation as a solid dispersion with a matrix polymer, such as copovidone, designed to improve the bioavailability of the poorly soluble drug (’396 Patent, col. 1:21-41).
  • Asserted Claims: The complaint asserts at least independent claim 1 (Compl. ¶71, ¶73).
  • Accused Features: The complaint alleges that Cipla’s ANDA Product is an immediate-release pharmaceutical composition comprising olaparib and certain excipients that infringes the claims of the ’396 Patent (Compl. ¶70, ¶73).

U.S. Patent No. 11,975,001 - Immediate Release Pharmaceutical Formulation of 4-[3-(4-Cyclopropanecarbonyl-Piperazine-1-Carbonyl)-4-Fluoro-Benzyl]-2H-Phthalazin-1-One

Issued May 7, 2024

  • Technology Synopsis: This patent is also part of the same family as the ’842 and ’396 patents and is directed to immediate-release pharmaceutical formulations of olaparib. It similarly claims compositions in the form of a solid dispersion containing olaparib and specific excipients to enhance its pharmaceutical properties (’001 Patent, col. 1:21-41).
  • Asserted Claims: The complaint asserts at least independent claim 1 (Compl. ¶88, ¶91).
  • Accused Features: The complaint alleges that Cipla's ANDA Product, as an immediate-release solid dispersion containing olaparib, will infringe the claims of the ’001 patent (Compl. ¶86, ¶91).

U.S. Patent No. 11,970,530 - Methods of Treating Homologous Recombination Deficient Cancer

Issued April 30, 2024

  • Technology Synopsis: This patent claims a method for treating specific cancers (ovarian, fallopian tube, peritoneal, or pancreatic) that are deficient in homologous recombination. The claimed method involves the combination therapy of administering both bevacizumab and olaparib (’530 Patent, col. 2:19-33).
  • Asserted Claims: The complaint asserts at least independent claim 1 (Compl. ¶106, ¶109).
  • Accused Features: The complaint alleges that the use of Cipla's ANDA Product as directed by its proposed labeling will infringe the claims by instructing the administration of olaparib for treating these specific cancers, which may be used in combination with bevacizumab (Compl. ¶104, ¶110).

III. The Accused Instrumentality

Product Identification

  • Cipla’s ANDA Product, identified as generic olaparib tablets of 100 mg and 150 mg strengths, submitted to the FDA under ANDA No. 219410 (Compl. ¶2, ¶28).

Functionality and Market Context

  • The complaint alleges that Cipla's ANDA Product is a generic version of Plaintiffs’ LYNPARZA® tablets and that Cipla’s ANDA contains bioavailability and/or bioequivalence studies to support this assertion (Compl. ¶28). LYNPARZA® is a commercially successful PARP inhibitor approved for the treatment of certain ovarian, breast, pancreatic, and prostate cancers (Compl. ¶27). Cipla allegedly seeks FDA approval to manufacture, use, and sell its generic version prior to the expiration of the patents-in-suit (Compl. ¶1-2).
  • No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

U.S. Patent No. 8,859,562 Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method of treatment of cancer in a patient, The proposed labeling for Cipla's ANDA Product allegedly directs its use for the treatment of certain cancers, such as ovarian, breast, pancreatic, and prostate cancer (Compl. ¶27). ¶42 col. 2:54-57
wherein the cancer cells of the patient are defective in Homologous Recombination (HR), The complaint alleges that methods of using LYNPARZA®, for which Cipla’s product is a generic version, are covered by the patent, implying the approved uses are for cancers with HR defects. ¶39, ¶40 col. 1:44-53
comprising administering to the patient a therapeutically effective amount of an inhibitor of poly(ADP-ribose) polymerase (PARP) activity. Cipla’s ANDA Product contains olaparib, a PARP inhibitor, and its proposed labeling allegedly directs administering it to patients in therapeutically effective amounts (Compl. ¶27-28). ¶42 col. 2:8-14

Identified Points of Contention

  • Scope Questions: A central question will be whether the specific indications for which Cipla seeks approval via its ANDA are exclusively for cancers where the cells are "defective in Homologous Recombination (HR)." The interpretation of this term, and whether it covers all patient populations included in Cipla’s proposed labeling, may be a point of dispute.
  • Technical Questions: In its Paragraph IV letter, Cipla did not contest infringement on any basis other than invalidity (Compl. ¶46). This suggests the primary battleground for this patent may be over validity (e.g., obviousness or anticipation) rather than a technical mismatch in infringement, though claim construction could still be dispositive.

U.S. Patent No. 8,475,842 Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
An immediate-release pharmaceutical composition Cipla's ANDA product is alleged to be an immediate-release pharmaceutical composition (Compl. ¶54). ¶54 col. 2:47-56
in the form of a solid dispersion The complaint alleges Cipla's ANDA Product is a solid dispersion comprising olaparib and certain excipients (Compl. ¶54). ¶54 col. 4:5-10
comprising 4-[3-(4-cyclopropanecarbonyl-piperazine-1-carbonyl)-4-fluoro-benzyl]-2H-phthalazin-1-one; and copovidone; The accused product is alleged to contain olaparib and excipients that meet the claim limitations (Compl. ¶28, ¶54). ¶54 col. 4:11-23
wherein the total concentration of [olaparib] in the composition is in the range of from 10% by weight to 40% by weight; Cipla's ANDA is for 100 mg and 150 mg tablets, and the complaint alleges on information and belief that the formulation will meet the claimed concentration ranges (Compl. ¶57). ¶57 col. 6:58-62
and wherein the weight ratio of [olaparib] to copovidone is in the range of from 1:1 to 1:9. The complaint alleges on information and belief that the ratio of olaparib to excipients in Cipla's ANDA Product will meet the claimed ratio limitations (Compl. ¶57). ¶57 col. 6:60-65

Identified Points of Contention

  • Scope Questions: The case may turn on the definition of "solid dispersion." What structural and physical characteristics must a formulation possess to meet this definition as used in the patent, and does Cipla’s formulation, which is not yet public, possess them?
  • Technical Questions: A key evidentiary question will be the precise composition of Cipla's ANDA Product. Discovery will be required to determine if it uses copovidone (or an equivalent) and if the weight percentages and ratios of drug-to-polymer fall within the claimed ranges, either literally or under the doctrine of equivalents.

V. Key Claim Terms for Construction

Term from ’562 Patent: "defective in Homologous Recombination (HR)"

Context and Importance

This term defines the entire patient population covered by the method claim. The scope of this term is critical because infringement depends on whether Cipla's proposed labeling directs use in patients whose cancers fall under this definition. Practitioners may focus on this term as its breadth could determine whether any non-infringing uses exist for Cipla's product.

Intrinsic Evidence for Interpretation

  • Evidence for a Broader Interpretation: The specification lists numerous proteins involved in the HR pathway, including BRCA1, BRCA2, RAD51, ATM, and others, stating that cells with a defect in any of these could be susceptible (’562 Patent, col. 4:1-17). This may support a broad construction covering defects in a wide range of HR-related genes.
  • Evidence for a Narrower Interpretation: The specification repeatedly uses BRCA1 and BRCA2 as primary examples of HR deficiency (’562 Patent, col. 4:31-36). A defendant might argue that the invention is centrally focused on these specific, well-known mutations and that the term's scope should be construed more narrowly around them or similar, clearly established HR defects.

Term from ’842 Patent: "solid dispersion"

Context and Importance

This term describes the fundamental structure of the claimed pharmaceutical formulation. Whether Cipla’s product infringes will depend on whether its formulation constitutes a "solid dispersion" as understood in the patent. This is a technical term of art whose precise meaning, especially regarding the degree of molecular mixing versus crystalline domains, will likely be a central point of contention.

Intrinsic Evidence for Interpretation

  • Evidence for a Broader Interpretation: The patent states that solid dispersions can include compositions where the drug is dispersed as discrete crystalline domains or as individual molecules within the carrier (’842 Patent, col. 8:64-col. 9:2). This could support a construction that does not require the drug to be fully amorphous or molecularly mixed.
  • Evidence for a Narrower Interpretation: The patent repeatedly emphasizes the goal of rendering the drug in a "stable amorphous form" to increase solubility and bioavailability (’842 Patent, col. 10:26-44). A defendant may argue that a true "solid dispersion" within the context of the patent requires the drug to be substantially or completely amorphous and molecularly dispersed, not merely a physical mixture with small crystalline particles.

VI. Other Allegations

Indirect Infringement

  • Plaintiffs allege both induced and contributory infringement for all five patents. The inducement theory is based on the allegation that Cipla knows and intends for its proposed product labeling to instruct physicians and patients to use the generic drug in a manner that directly infringes the method claims (e.g., ’562 and ’530 patents) and infringes by making and using the claimed compositions (e.g., ’842, ’396, ’001 patents) (Compl. ¶43, ¶59). The basis for contributory infringement is that Cipla's product and its labeling are especially made for an infringing use and are not suitable for substantial non-infringing use (Compl. ¶43, ¶60).

Willful Infringement

  • For each patent, the complaint alleges that Cipla has acted with "full knowledge" of the patent and "without a reasonable basis for believing that it would not be liable for the infringement" (Compl. ¶45, ¶62, ¶78, ¶96, ¶114). This knowledge is allegedly based on the patents being listed in the FDA's Orange Book and on Cipla’s own Paragraph IV notice letter, which acknowledged the patents.

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

  • A core issue will be one of definitional scope: For the method-of-use patents, can the term "defective in Homologous Recombination," which has a specific biological meaning, be construed to cover all patient populations for which Cipla’s generic olaparib will be indicated? The answer will determine the extent of overlap between the patent claims and the accused conduct.
  • A key evidentiary question will be one of compositional identity: For the formulation patents, does Cipla’s ANDA product, once its full composition is revealed, meet the specific limitations of a "solid dispersion" containing "copovidone" at the claimed concentrations and ratios, or is there a fundamental mismatch in its formulation technology that places it outside the claims?
  • A central theme of the litigation, as foreshadowed by Cipla's Paragraph IV certification, will be the validity of the asserted claims. This will raise questions of whether the patented methods and formulations were obvious or anticipated by the state of the art at the time of their respective inventions, a defense that is asserted by Cipla but not detailed in the complaint itself.