DCT

1:22-cv-01277

Array Biopharma Inc v. Alembic Pharma Ltd

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:22-cv-01277, D. Del., 09/28/2022
  • Venue Allegations: Plaintiff alleges venue is proper in the District of Delaware because Defendant Alembic Pharmaceuticals, Inc. is a Delaware corporation and because Defendants' submission of an Abbreviated New Drug Application (ANDA) constitutes a tortious act of patent infringement that will cause foreseeable harm to Plaintiff in Delaware.
  • Core Dispute: Plaintiff alleges that Defendants' submission of an ANDA to the FDA seeking approval to market a generic version of Plaintiff's cancer drug MEKTOVI (binimetinib) constitutes an act of infringement of six U.S. patents.
  • Technical Context: The technology concerns small molecule compounds that inhibit protein kinases (specifically MEK and B-Raf), which are key components of cellular signaling pathways implicated in the growth of certain cancers like melanoma.
  • Key Procedural History: This action was initiated under the Hatch-Waxman Act following Defendants' submission of ANDA No. 217678 and a subsequent Paragraph IV notice letter to Plaintiff, in which Defendants certified that the patents-in-suit are invalid, unenforceable, and/or will not be infringed by the proposed generic product. The patents-in-suit are listed in the FDA’s “Approved Drug Products with Therapeutic Equivalence Evaluations” (the “Orange Book”) for MEKTOVI.

Case Timeline

Date Event
2009-08-28 Earliest Priority Date for ’464, ’229, and ’761 Patents
2012-10-19 Earliest Priority Date for ’016, ’376, and ’944 Patents
2016-04-19 U.S. Patent No. 9,314,464 Issues
2017-02-07 U.S. Patent No. 9,562,016 Issues
2017-03-21 U.S. Patent No. 9,598,376 Issues
2017-12-26 U.S. Patent No. 9,850,229 Issues
2018-05-29 U.S. Patent No. 9,980,944 Issues
2018-06-26 U.S. Patent No. 10,005,761 Issues
2022-08-15 Alembic sends Paragraph IV Notice Letter
2022-09-28 Complaint Filed

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

U.S. Patent No. 9,314,464 - “Compounds and Compositions as Protein Kinase Inhibitors”

The Invention Explained

  • Problem Addressed: The patent family addresses diseases associated with abnormal or deregulated protein kinase activity, particularly those involving the B-Raf kinase, which plays a central role in cellular signaling pathways that can lead to cancer when mutated ('464 Patent, col. 1:19-24, 35-42).
  • The Patented Solution: The invention provides methods of treating B-Raf-mediated cancers by administering a B-Raf protein kinase inhibitor in combination with a MEK protein kinase inhibitor, such as binimetinib. This dual-inhibition approach targets two different points in the same critical cell-growth pathway (the Ras-Raf-MEK-ERK pathway), a strategy intended to produce a more effective anti-cancer response ('464 Patent, Abstract; col. 9:1-9).
  • Technical Importance: The discovery that specific mutations in the BRAF gene, such as V600E, are drivers in a significant percentage of melanomas established B-Raf as a key therapeutic target in oncology ('464 Patent, col. 9:13-31).

Key Claims at a Glance

  • The complaint asserts at least claim 10 (dependent on claim 1) (Compl. ¶52).
  • The essential elements of independent claim 1, as narrowed by dependent claim 10, are:
    • A method of treating melanoma having a BRAF V600 mutation in a patient.
    • Comprising administering to the patient a therapeutically effective amount of the B-Raf protein kinase inhibitor encorafenib.
    • In combination with a therapeutically effective amount of the MEK inhibitor binimetinib, or a pharmaceutically acceptable salt thereof.

U.S. Patent No. 9,850,229 - “Compounds and Compositions as Protein Kinase Inhibitors”

The Invention Explained

  • Problem Addressed: This patent, part of the same family as the ’464 patent, also addresses the treatment of cancers driven by aberrant B-Raf kinase activity ('229 Patent, col. 1:19-24).
  • The Patented Solution: The patent claims a specific method for treating melanoma characterized by a BRAF V600E or V600K mutation. The claimed solution is the administration of a combination therapy comprising encorafenib (a B-Raf inhibitor) and binimetinib (a MEK inhibitor) ('229 Patent, Abstract; col. 4:50-65).
  • Technical Importance: The claimed method provides a targeted therapy specifically for melanoma patients whose tumors carry certain BRAF mutations, representing a shift toward personalized cancer medicine based on the genetic profile of a patient's tumor ('229 Patent, col. 9:13-31).

Key Claims at a Glance

  • The complaint asserts at least claim 1 (Compl. ¶63).
  • The essential elements of independent claim 1 are:
    • A method for treating melanoma in a patient.
    • Wherein the melanoma has a BRAF V600E or V600K mutation.
    • Comprising administering to the patient a combination of encorafenib, or a pharmaceutically acceptable salt thereof, and binimetinib, or a pharmaceutically acceptable salt thereof.

U.S. Patent No. 10,005,761 - "Compounds and Compositions as Protein Kinase Inhibitors"

  • Technology Synopsis: The ’761 Patent, part of the same family as the ’464 and ’229 patents, is also directed to methods of treating B-Raf mediated cancers by administering a B-Raf inhibitor in combination with a MEK inhibitor (Compl. ¶27; '761 Patent, Abstract).
  • Asserted Claims: At least claim 11 is asserted (Compl. ¶75).
  • Accused Features: The accused features are Defendants' proposed generic binimetinib tablets and the proposed labeling that allegedly instructs their use in combination with encorafenib to treat melanoma, thereby practicing the patented method (Compl. ¶¶71, 75).

U.S. Patent No. 9,562,016 - "Preparation of and Formulation Comprising a MEK Inhibitor"

  • Technology Synopsis: The ’016 Patent is directed to a specific crystalline form of binimetinib and to pharmaceutical compositions that include this crystalline form. The stability and dissolution properties of a specific crystalline form of a drug can be critical for its formulation and therapeutic efficacy (Compl. ¶29; '016 Patent, Abstract).
  • Asserted Claims: At least claim 3 is asserted (Compl. ¶83).
  • Accused Features: The complaint alleges that Defendants' generic tablets, which contain binimetinib, will infringe the claims directed to pharmaceutical compositions comprising crystalline binimetinib (Compl. ¶83).

U.S. Patent No. 9,598,376 - "Preparation of and Formulation Comprising a MEK inhibitor"

  • Technology Synopsis: The ’376 Patent, related to the ’016 patent, is directed to methods of treating cancer in a patient by administering a therapeutically effective amount of crystalline binimetinib (Compl. ¶31; '376 Patent, Abstract).
  • Asserted Claims: At least claim 1 is asserted (Compl. ¶91).
  • Accused Features: The complaint alleges that the use of Defendants' generic tablets as directed by the proposed labeling will infringe the claimed method of using crystalline binimetinib to treat cancer (Compl. ¶¶88, 91).

U.S. Patent No. 9,980,944 - "Preparation of and Formulation Comprising a MEK inhibitor"

  • Technology Synopsis: The ’944 Patent, also related to the ’016 and ’376 patents, is directed to methods of treating melanoma by administering crystallized binimetinib (Compl. ¶33; '944 Patent, Abstract).
  • Asserted Claims: At least claim 1 is asserted (Compl. ¶102).
  • Accused Features: The complaint alleges that the use of Defendants' generic tablets as directed by the proposed labeling for treating melanoma will infringe the claimed method (Compl. ¶¶99, 102).

III. The Accused Instrumentality

  • Product Identification: The accused instrumentality is the generic drug product described in Alembic's ANDA No. 217678, identified as "Alembic Generic Tablets," which are 15 mg tablets of binimetinib (Compl. ¶¶10, 41).
  • Functionality and Market Context: The Alembic Generic Tablets contain binimetinib as the active pharmaceutical ingredient, which is a reversible inhibitor of MEK1 and MEK2 protein kinases (Compl. ¶19). The complaint provides the chemical structure of binimetinib, the active ingredient in both the brand-name and accused generic products (Compl. p. 5). The proposed labeling submitted with the ANDA allegedly copies the indication from Plaintiff's MEKTOVI label, stating the product is for use in combination with encorafenib for the treatment of patients with unresectable or metastatic melanoma having a BRAF V600E or V600K mutation (Compl. ¶49). The product is intended for commercial sale in the United States prior to the expiration of the patents-in-suit, creating the basis for this Hatch-Waxman litigation (Compl. ¶2).

IV. Analysis of Infringement Allegations

’464 Patent Infringement Allegations

Claim Element (from Independent Claim 1, as narrowed by Dependent Claim 10) Alleged Infringing Functionality Complaint Citation Patent Citation
A method of treating melanoma having a BRAF V600 mutation in a patient in need thereof The proposed labeling for the Alembic Generic Tablets allegedly indicates the product for the treatment of patients with unresectable or metastatic melanoma with a BRAF V600E or V600K mutation. ¶49 col. 29:1-12
comprising administering to the patient a therapeutically effective amount of the B-Raf protein kinase inhibitor encorafenib The proposed labeling allegedly instructs use of the generic binimetinib tablets in combination with encorafenib. ¶49 col. 29:1-12
in combination with a therapeutically effective amount of the MEK inhibitor binimetinib, or a pharmaceutically acceptable salt thereof The accused product is a tablet containing binimetinib, and its proposed labeling allegedly directs its use in combination with encorafenib. ¶¶41, 49 col. 29:1-12
  • Identified Points of Contention:
    • Scope Questions: The complaint alleges infringement based on the instructions in the proposed label. A potential issue for the court is whether the language of the label is sufficient to induce infringement of every limitation of the asserted claims. For the formulation patents (’016, ’376, ’944), a question arises as to whether the generic product contains the specific "crystalline" form of binimetinib as claimed.
    • Technical Questions: The complaint does not provide sufficient detail for analysis of the crystalline form of binimetinib in the accused product. The determination of infringement for the ’016, ’376, and ’944 patents will likely depend on technical evidence, such as X-ray powder diffraction data, comparing the crystalline structure of the binimetinib in Alembic's tablets to that defined in the patents.

’229 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method for treating melanoma in a patient, wherein the melanoma has a BRAF V600E or V600K mutation The proposed labeling for the Alembic Generic Tablets allegedly indicates the product for the treatment of patients with melanoma having a BRAF V600E or V600K mutation. ¶60 col. 28:53-56
comprising administering to the patient a combination of encorafenib ... and binimetinib The accused product contains binimetinib, and its proposed label allegedly instructs its administration in combination with encorafenib. ¶¶41, 60 col. 28:57-61
  • Identified Points of Contention:
    • Scope Questions: As with the ’464 patent, a central question will be whether the act of seeking FDA approval for a product with the proposed label constitutes an act of infringement under 35 U.S.C. § 271(e)(2). The analysis will focus on whether the label encourages, recommends, or promotes an infringing use.
    • Technical Questions: The infringement analysis for this method-of-use claim is primarily a legal question based on the interpretation of the proposed label, rather than a technical one about the product's physical properties.

V. Key Claim Terms for Construction

  • The Term: "in combination with"
  • Context and Importance: This term appears in the asserted method claims of the ’464, ’229, and ’761 patents and is central to defining the infringing act. Its construction will determine whether the claimed method requires simultaneous administration, administration in a single composition, or if it also covers sequential administration as part of a coordinated therapeutic regimen. Practitioners may focus on this term because a narrow construction could provide a basis for a non-infringement argument if the accused label does not explicitly require a specific mode of co-administration.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The specification of the related ’761 Patent explicitly defines "co-administration" or "combined administration" to "encompass administration of the selected therapeutic agents to a single patient, and are intended to include treatment regimens in which the agents are not necessarily administered by the same route of administration or at the same time" ('761 Patent, col. 12:41-48).
    • Evidence for a Narrower Interpretation: The specific examples in the patents describe pre-clinical studies where administration of the combined agents was likely simultaneous or nearly so, which could be argued to support a more limited temporal scope than the express definition provided in the specification ('761 Patent, Example 130).

VI. Other Allegations

  • Indirect Infringement: The complaint's primary theory for the method-of-use claims is indirect infringement. It alleges that by seeking approval to market its generic tablets with a label that copies the approved indications for MEKTOVI, Defendants are actively inducing infringement by instructing physicians to prescribe, and patients to use, the generic product in a manner that directly infringes the asserted claims (Compl. ¶¶53, 64, 74, 92, 103). The complaint also alleges contributory infringement, stating that the generic tablets and their labeling are especially made for an infringing use and are not suitable for substantial noninfringing use (Compl. ¶¶55, 66, 77, 94, 105).
  • Willful Infringement: While not using the word "willful," the complaint alleges that Defendants had knowledge of the patents-in-suit when they submitted the ANDA, based on the patents' listing in the Orange Book and the statutory requirement for a Paragraph IV certification (Compl. ¶¶50, 61, 72, 82, 89, 100). These allegations could form the basis for a claim of enhanced damages should infringement be found after the generic product launches.

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

  • A central issue will be one of induced infringement: does the specific language in Alembic's proposed product label actively encourage, recommend, or promote the administration of its generic binimetinib tablets in combination with encorafenib in a manner that satisfies all limitations of the asserted method claims?
  • A key evidentiary question for the patents claiming specific formulations will be whether the binimetinib in Alembic’s ANDA product is the same "crystalline" form as recited in the claims of the ’016, ’376, and ’944 patents. This will likely require expert analysis of competing technical data from both parties.
  • The case may also turn on a question of validity: although the complaint states Defendants' detailed statement focused on non-infringement, the underlying Paragraph IV certification alleges invalidity and/or unenforceability, raising the possibility that Defendants will challenge the novelty or non-obviousness of the patented methods and compositions.