DCT

1:20-cv-01009

AbbVie Inc v. Alembic Pharma Ltd

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:20-cv-01009, D. Del., 09/17/2020
  • Venue Allegations: Venue is alleged based on Defendant Alembic Pharmaceuticals, Inc.'s incorporation in Delaware, and the other foreign-based defendants' substantial contacts with the United States and intent to market the accused generic product in Delaware.
  • Core Dispute: Plaintiffs allege that Defendants' submission of an Abbreviated New Drug Application (ANDA) to the FDA, seeking approval to market a generic version of the cancer drug VENCLEXTA® (venetoclax), constitutes an act of infringement of two patents covering specific crystalline forms of the active ingredient.
  • Technical Context: The technology relates to specific crystalline solid-state forms (polymorphs) of venetoclax, a B-cell lymphoma 2 (BCL-2) inhibitor used to treat certain types of leukemia and lymphoma.
  • Key Procedural History: The action was initiated under the Hatch-Waxman Act following Plaintiffs' receipt of notice letters from Alembic, dated June 16, 2020, and September 4, 2020, which advised of the filing of ANDA No. 214747 and certified that the patents-in-suit would not be infringed by the proposed generic product.

Case Timeline

Date Event
2010-11-23 Priority Date for '657 and '873 Patents
2014-05-13 U.S. Patent No. 8,722,657 Issued
2016-04-11 VENCLEXTA® First Approved by FDA
2020-06-16 Plaintiffs Receive Alembic's First Notice Letter for ANDA
2020-08-04 U.S. Patent No. 10,730,873 Issued
2020-09-04 Plaintiffs Receive Alembic's Second Notice Letter
2020-09-17 First Amended Complaint Filed

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

U.S. Patent No. 8,722,657 - "Salts and Crystalline Forms of an Apoptosis-Inducing Agent," issued May 13, 2014

The Invention Explained

  • Problem Addressed: The patent describes that while apoptosis-inducing agents targeting the Bcl-2 protein family are promising cancer therapies, the amorphous form of such compounds can be difficult and expensive to purify and may present process control problems for pharmaceutical formulation (’657 Patent, col. 3:20-29).
  • The Patented Solution: The invention provides novel, stable crystalline forms of the active pharmaceutical ingredient (API) known as "Compound 1" (venetoclax). These specific crystalline structures, identifiable by their unique powder X-ray diffraction (PXRD) patterns, are designed to improve the physicochemical properties of the API, such as stability, solubility, and ease of handling, making them suitable for use in oral dosage forms like tablets (’657 Patent, col. 3:30-46; FIG. 1).
  • Technical Importance: Developing a specific, stable, and reproducible crystalline form of a drug substance is a critical step in pharmaceutical development, as it ensures consistency in manufacturing, bioavailability, and shelf-life for the final drug product (’657 Patent, col. 3:50-59).

Key Claims at a Glance

  • The complaint asserts "one or more claims" of the patent (Compl. ¶67). Independent claim 1 is representative:
  • A compound... (Compound 1)... in a crystalline form wherein the crystalline form is Compound 1 free base anhydrate,
  • characterized by a powder X-ray diffraction pattern having five or more peaks selected from those at 6.3, 7.1, 9.0, 9.5, 12.5, 14.5, 14.7, 15.9, 16.9, and 18.9 degrees 2θ (pattern A)... (’657 Patent, col. 39:11-21).
  • The complaint reserves the right to assert other claims, which would include dependent claims.

U.S. Patent No. 10,730,873 - "Salts and Crystalline Forms of an Apoptosis-Inducing Agent," issued August 4, 2020

The Invention Explained

  • Problem Addressed: As a continuation of the same research program, this patent addresses the same technical challenge: the need for stable, well-characterized forms of the venetoclax compound suitable for pharmaceutical development, as an alternative to a potentially problematic amorphous state (’873 Patent, col. 1:39-col. 2:54).
  • The Patented Solution: The ’873 Patent discloses and claims additional novel crystalline forms of Compound 1 (venetoclax), including specific hydrate forms. Like the '657 Patent, these forms are distinguished by their unique PXRD patterns and are intended to provide favorable properties for creating a consistent and effective oral drug product (’873 Patent, Abstract; col. 4:35-50). The specification describes a variety of solvate and hydrate forms, including the one claimed in Claim 1 (’873 Patent, col. 24:14-30; FIG. 4).
  • Technical Importance: By identifying multiple distinct crystalline forms, the patent provides drug formulators with a portfolio of options, each with potentially different properties (e.g., dissolution rate, stability) that can be optimized for a final pharmaceutical composition (’873 Patent, col. 4:35-46).

Key Claims at a Glance

  • The complaint asserts "one or more claims" of the patent (Compl. ¶75). Independent claim 1 is representative:
  • A compound... (Compound 1)... in a crystalline form, wherein the crystalline form is Compound 1 free base hydrate,
  • characterized by a powder X-ray diffraction pattern having five or more peaks selected from those at 3.3, 6.4, 7.1, 7.3, 10.1, 11.4, 13.2, 14.4, 14.6, 15.1, 15.8, 16.2, 17.2, 17.6, 18.0, 18.6, 19.0, 19.5, 19.8, 20.2, 20.7, 21.0, 22.5, 23.0, 26.0, 28.9, and 29.2 degrees 2θ (pattern D)... (’873 Patent, col. 37:57-col. 38:2).
  • The complaint reserves the right to assert other claims.

III. The Accused Instrumentality

Product Identification

  • Defendants' proposed generic venetoclax tablets, as described in Abbreviated New Drug Application (ANDA) No. 214747 ("Alembic's Generic Version") (Compl. ¶¶1, 23).

Functionality and Market Context

  • The complaint alleges that Alembic's ANDA seeks approval to manufacture and sell generic venetoclax tablets in 10 mg, 50 mg, and 100 mg dosage strengths (Compl. ¶47). This mirrors the dosage strengths of Plaintiffs' branded product, VENCLEXTA® (Compl. ¶49). The infringement alleged is the statutory act of submitting the ANDA to the FDA for a product that, if approved and marketed, would infringe the patents-in-suit (Compl. ¶¶68, 76).
  • The complaint positions VENCLEXTA® as a "highly successful" and "ground-breaking" drug for treating chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), and acute myeloid leukemia (AML), having been used to treat over 31,000 patients (Compl. ¶¶1-2).

IV. Analysis of Infringement Allegations

The complaint alleges infringement under 35 U.S.C. § 271(e)(2)(A), which defines the submission of an ANDA seeking approval to market a generic version of a patented drug as an act of infringement. The core allegation is that the product described in Alembic's ANDA, if marketed, will contain a crystalline form of venetoclax covered by the asserted claims.

No probative visual evidence provided in complaint.

'657 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A compound 4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl)amino]phenyl}sulfonyl)-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide (Compound 1) in a crystalline form wherein the crystalline form is Compound 1 free base anhydrate... The complaint alleges on information and belief that "Alembic's Generic Version" will contain the active ingredient venetoclax (Compound 1) and will infringe one or more claims of the ’657 Patent. The complaint does not contain specific facts demonstrating this element but alleges it based on the ANDA filing. ¶47, ¶67 col. 3:62-col. 4:4
...characterized by a powder X-ray diffraction pattern having five or more peaks selected from those at 6.3, 7.1, 9.0, 9.5, 12.5, 14.5, 14.7, 15.9, 16.9, and 18.9 degrees 2θ... The complaint alleges on information and belief that the venetoclax in Alembic's Generic Version will have a crystalline form that exhibits the claimed PXRD pattern. ¶67 col. 23:41-col. 24:1

'873 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A compound 4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl)amino]phenyl}sulfonyl)-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide (Compound 1) in a crystalline form, wherein the crystalline form is Compound 1 free base hydrate... The complaint alleges on information and belief that "Alembic's Generic Version" will contain the active ingredient venetoclax (Compound 1) and will infringe one or more claims of the ’873 Patent. The complaint does not contain specific facts demonstrating this element but alleges it based on the ANDA filing. ¶48, ¶75 col. 3:62-col. 4:4
...characterized by a powder X-ray diffraction pattern having five or more peaks selected from those at 3.3, 6.4, 7.1, 7.3, 10.1, 11.4, 13.2, 14.4, 14.6, 15.1, 15.8, 16.2, 17.2, 17.6, 18.0, 18.6, 19.0, 19.5, 19.8, 20.2, 20.7, 21.0, 22.5, 23.0, 26.0, 28.9, and 29.2 degrees 2θ... The complaint alleges on information and belief that the venetoclax in Alembic's Generic Version will have a crystalline form that exhibits the claimed PXRD pattern. ¶75 col. 24:14-30

Identified Points of Contention

  • Factual Question: The central dispute will be factual: what is the actual polymorphic form of the venetoclax API in the product described in Alembic's ANDA? The complaint notes that Alembic's notice letters certified non-infringement, suggesting Alembic will argue its API is a different, non-infringing polymorph or an amorphous form (Compl. ¶51). The case will likely depend on competing expert analyses of the accused product.
  • Scope Question: A potential dispute may arise over the scope of the term "characterized by." Does the PXRD pattern of an accused product need to match the claimed peaks exactly, or is there an acceptable range of experimental error? The patents state that PXRD peak positions are typically ±0.2 degrees 2θ, which may become a point of contention during expert testimony (’873 Patent, col. 19:34-35).

V. Key Claim Terms for Construction

  • The Term: "characterized by a powder X-ray diffraction pattern having five or more peaks selected from..." (appearing in Claim 1 of both patents)
  • Context and Importance: This phrase is the defining feature of the claimed inventions. The infringement analysis will hinge entirely on whether the venetoclax in Alembic's generic product has a PXRD pattern that meets this limitation. Practitioners may focus on this term because the presence or absence of a specific set of diffraction peaks is the dispositive test for infringement of a polymorph claim. The dispute will be less about the meaning of the words and more about the application of analytical chemistry techniques to the facts.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: A party arguing for infringement may contend that the claim language is clear and requires only that any five peaks from the listed set are present in the accused product's PXRD pattern, within a standard experimental tolerance (e.g., ±0.2 degrees 2θ). The specification supports this by providing lists of peaks for each form and then claiming a subset thereof, suggesting the full pattern is not required for infringement (’657 Patent, col. 23:61-col. 24:1).
    • Evidence for a Narrower Interpretation: A party arguing for non-infringement might suggest that the term "characterized by" implies that the recited peaks must be the primary, or most intense, defining peaks of that crystalline form. They could point to the patent's figures (e.g., ’657 Patent, FIG. 1) showing the full diffraction pattern with relative intensities and argue that a product whose pattern lacks the same prominent features, even if it has five of the listed peaks as minor signals, is not the same crystalline form. This could raise the question of whether the claimed product is a mixture of polymorphs where the patented form is only a trace component.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges that upon approval, Alembic will induce and contribute to infringement under 35 U.S.C. § 271(b) and (c) by marketing and selling its generic product with labeling that encourages its use for patented indications (Compl. ¶¶69, 77). The factual basis is the proposed commercialization of a bioequivalent drug for the same uses as VENCLEXTA®.
  • Willful Infringement: The complaint alleges that Alembic had "actual and constructive notice" of the '657 Patent prior to filing its ANDA and of the '873 Patent since its issuance, and that proceeding with the ANDA despite this knowledge constitutes willful infringement (Compl. ¶¶70, 78).

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

This Hatch-Waxman action will primarily turn on a central evidentiary question and its interpretation under patent law.

  • A core issue will be one of polymorphic identity: Does the venetoclax API in the product specified in Alembic's ANDA actually exhibit the powder X-ray diffraction patterns recited in the asserted claims of the '657 and '873 patents? The resolution will depend on a highly technical, fact-intensive battle of analytical chemistry experts.
  • A related evidentiary question will be one of purity and detection: If the accused product is found to be a mixture of forms, what quantity of a patented crystalline form must be present to constitute infringement of a claim to that form? This raises the question of whether the presence of trace amounts of a patented polymorph is sufficient for infringement, or if the patented form must be the predominant or characterizing form in the API.