DCT

1:21-cv-02258

AbbVie Inc v. Alvotech HF

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:21-cv-02258, N.D. Ill., 04/27/2021
  • Venue Allegations: Venue is alleged to be proper because the Defendant is a foreign entity and therefore subject to suit in any U.S. judicial district.
  • Core Dispute: Plaintiff alleges that Defendant’s submission of an abbreviated Biologics License Application (aBLA) to the FDA for its proposed biosimilar of HUMIRA® constitutes a statutory act of infringement of four patents related to adalimumab formulations and methods of treatment.
  • Technical Context: The technology concerns biologic drugs, specifically high-concentration formulations of the monoclonal antibody adalimumab, a widely-used treatment for various autoimmune diseases.
  • Key Procedural History: The litigation arises under the Biologics Price Competition and Innovation Act (BPCIA), following a statutory information exchange where Plaintiff identified 62 patents it believed would be infringed, from which Defendant selected four for this initial phase of litigation. The complaint notes that U.S. Patent No. 9,085,619 and a related family member of U.S. Patent No. 8,961,973 were previously challenged in inter partes review (IPR) proceedings at the Patent Trial and Appeal Board (PTAB), and their validity was upheld.

Case Timeline

Date Event
2004-04-09 Priority Date for U.S. Patent No. 8,961,973
2006-06-08 Priority Date for U.S. Patent No. 8,926,975
2007-11-30 Priority Date for U.S. Patent Nos. 8,420,081 and 9,085,619
2013-04-16 U.S. Patent No. 8,420,081 Issued
2015-01-06 U.S. Patent No. 8,926,975 Issued
2015-02-24 U.S. Patent No. 8,961,973 Issued
2015-07-21 U.S. Patent No. 9,085,619 Issued
2018-05-21 Clinical trial start date for accused product AVT02
2020-09-01 Accused aBLA submitted to FDA (approximate date)
2020-11-05 FDA accepted accused aBLA for review (on or before this date)
2021-04-27 Complaint Filed

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

U.S. Patent No. 8,420,081 - "Antibody Formulations and Methods of Making Same"

  • Patent Identification: U.S. Patent No. 8,420,081, "Antibody Formulations and Methods of Making Same," issued April 16, 2013 (Compl. ¶63).

The Invention Explained

  • Problem Addressed: The patent’s background describes the technical difficulties in creating high-concentration protein formulations for therapeutic use. At high concentrations, proteins like antibodies are prone to degradation, aggregation, and increased viscosity, which can compromise stability, shelf-life, and the ability to administer the drug, particularly via subcutaneous injection (’081 Patent, col. 2:50-65).
  • The Patented Solution: The invention is based on the discovery that a stable, high-concentration aqueous protein formulation can be achieved with low levels of ionic excipients or without any buffers. The patented solution involves using a diafiltration process with water to remove salts and buffering agents, resulting in a formulation with low conductivity and low osmolality that maintains the protein's stability and biological activity (’081 Patent, Abstract; col. 3:24-46).
  • Technical Importance: This approach enables the delivery of a high dose of a biologic drug in a small volume, which is critical for making subcutaneous self-administration by patients more convenient and tolerable (Compl. ¶¶9-10).

Key Claims at a Glance

  • The complaint asserts claims 25, 33, 57-61, 63-67, 84, 86-89, 91-93, and 95-99 of the ’081 patent (Compl. ¶88). Independent claim 57 is representative of the asserted formulation claims.
  • Independent Claim 57 Elements:
    • An aqueous formulation
    • comprising an antibody, or an antigen-binding fragment thereof, at a concentration of at least about 50 mg/ml
    • and water
    • wherein the formulation has a conductivity of less than about 2.5 mS/cm
  • The complaint reserves the right to assert additional claims, including dependent claims (Compl. ¶88).

U.S. Patent No. 8,926,975 - "Method of Treating Ankylosing Spondylitis"

  • Patent Identification: U.S. Patent No. 8,926,975, "Method of Treating Ankylosing Spondylitis," issued January 6, 2015 (Compl. ¶68).

The Invention Explained

  • Problem Addressed: The patent describes ankylosing spondylitis (AS) as a chronic, progressive inflammatory disease of the axial skeleton and large peripheral joints that causes pain, stiffness, and loss of mobility, for which effective treatments were needed (’975 Patent, col. 1:16-33).
  • The Patented Solution: The invention provides methods for treating AS by administering a specific human TNFα antibody, adalimumab, at a defined dosage and frequency. The claimed method is intended to reduce the signs and symptoms of AS, decrease pain and fatigue, and induce partial remission of the disease (’975 Patent, Abstract; col. 2:2-15).
  • Technical Importance: This patent covers a specific therapeutic use for adalimumab, providing a targeted biologic treatment option for a debilitating inflammatory condition (Compl. ¶8).

Key Claims at a Glance

  • The complaint asserts claims 1-6 of the ’975 patent (Compl. ¶99). Claim 1 is the sole independent claim.
  • Independent Claim 1 Elements:
    • A method of treating active ankylosing spondylitis (AS) in a subject having total spinal ankylosis
    • comprising selecting a subject having active AS and total spinal ankylosis
    • and subcutaneously administering 40 mg of an isolated human anti-TNFα antibody to the subject once every other week
    • wherein the human anti-TNFα antibody comprises a light chain variable region (LCVR) comprising the amino acid sequence of SEQ ID NO: 1 and a heavy chain variable region (HCVR) comprising the amino acid sequence of SEQ ID NO: 2

U.S. Patent No. 8,961,973 - "Multiple-Variable Dose Regimen for Treating TNFα-Related Disorders"

  • Patent Identification (Multi-Patent Capsule): U.S. Patent No. 8,961,973, "Multiple-Variable Dose Regimen for Treating TNFα-Related Disorders," issued February 24, 2015 (Compl. ¶72).
  • Technology Synopsis: The patent addresses the need for safe and effective treatments for TNFα-related disorders like Crohn's disease (’973 Patent, col. 2:22-31). The invention is a method of treatment using a multiple-variable dose regimen, which involves administering a higher initial "induction dose" to quickly achieve a therapeutic level of a TNFα inhibitor, followed by administering lower "treatment doses" for maintenance (’973 Patent, Abstract).
  • Asserted Claims: Claims 1-30 are asserted (Compl. ¶112).
  • Accused Features: The complaint alleges that Alvotech’s biosimilar product, upon approval, will be administered according to a dosage and method that will induce infringement of the patent (Compl. ¶112).

U.S. Patent No. 9,085,619 - "Anti-TNF Antibody Formulations"

  • Patent Identification (Multi-Patent Capsule): U.S. Patent No. 9,085,619, "Anti-TNF Antibody Formulations," issued July 21, 2015 (Compl. ¶77).
  • Technology Synopsis: This patent, related to the ’081 patent, addresses the problem of maintaining stability in high-concentration antibody formulations (’619 Patent, col. 2:1-19). The invention is a stable, aqueous antibody formulation with a high protein concentration (e.g., 50 mg/mL) that is essentially free of a buffer and has a low concentration of non-ionic surfactant (’619 Patent, Abstract).
  • Asserted Claims: Claims 1-5 and 16-30 are asserted (Compl. ¶125).
  • Accused Features: The formulation of Alvotech's aBLA Product is alleged to directly infringe the claims (Compl. ¶¶125-126).

III. The Accused Instrumentality

Product Identification

  • The accused instrumentality is Alvotech’s proposed biosimilar adalimumab product, designated AVT02 (Compl. ¶¶28, 52). The action is based on Alvotech's submission of abbreviated Biologics License Application (aBLA) No. 761205 to the U.S. Food and Drug Administration (FDA) (Compl. ¶41).

Functionality and Market Context

  • AVT02 is identified as a monoclonal antibody (mAb) proposed as a biosimilar to AbbVie's HUMIRA® product (Compl. ¶55). The product is described as a "high concentration (100mg/mL) dosage form," which matches the "newest dosage forms of the reference product" HUMIRA® (Compl. ¶55). The complaint alleges that Alvotech seeks to copy AbbVie's innovations to enter the U.S. biosimilar market (Compl. ¶¶2, 6).
  • No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The complaint does not contain claim charts or detailed infringement theories mapping elements of the accused product to specific claim limitations. It alleges that infringement is evident from confidential information Alvotech disclosed to AbbVie as part of the BPCIA process, including the contents of its aBLA and manufacturing information (Compl. ¶¶87, 98, 111, 124). The complaint states that detailed claim-by-claim infringement contentions were provided to Alvotech but does not include them in the public filing (Compl. ¶¶88, 99, 112, 125). This precludes a detailed claim chart analysis.

  • Identified Points of Contention:
    • For the Formulation Patents (’081 and ’619): A primary technical question will be whether the specific formulation of AVT02, as detailed in the confidential aBLA, possesses the physical and chemical properties required by the asserted claims. This may involve disputes over whether the AVT02 formulation meets the claimed parameters for protein concentration, conductivity, and the absence of buffers.
    • For the Method of Use Patents (’975 and ’973): The infringement analysis will likely center on inducement. A key question will be whether Alvotech's proposed product labeling and marketing materials will instruct or encourage medical professionals and patients to administer AVT02 in a manner that directly infringes the claimed methods. This raises a scope question: does Alvotech's proposed indication for treating ankylosing spondylitis read on the specific patient population of "subject[s] having total spinal ankylosis" as required by claim 1 of the ’975 Patent?

V. Key Claim Terms for Construction

  • The Term: "conductivity of less than about 2.5 mS/cm" (from claim 57 of the ’081 Patent)

  • Context and Importance: This term is central to defining the scope of the patented low-ionic formulation. The precise numerical boundary, particularly as modified by "about," will be critical to the infringement analysis, as the accused product's conductivity may be near this value.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The specification discloses formulations with conductivity "of less than about 1.5 mS/cm," "less than about 1.0 mS/cm," and "less than about 0.5 mS/cm" (’081 Patent, col. 4:26-32). A party might argue that "about 2.5 mS/cm" was chosen as a claim limit to encompass a range consistent with the inventive concept of a low-ionic formulation, rather than being strictly limited to the exemplified values.
    • Evidence for a Narrower Interpretation: The specification describes a specific method for measuring conductivity (’081 Patent, col. 9:1-12). A party could contend that this implies a high degree of precision and that "about" should not be interpreted to significantly expand the numerical limit beyond what measurement variability would permit.

  • The Term: "total spinal ankylosis" (from claim 1 of the ’975 Patent)

  • Context and Importance: This term defines the specific patient sub-population for the patented treatment method. The construction of this term will be critical for the induced infringement analysis, as it determines whether Alvotech’s proposed label for treating ankylosing spondylitis will direct use in a manner that infringes.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The patent does not provide an explicit definition in the specification. A party may argue the term should be given its plain and ordinary meaning to a person skilled in rheumatology. The patent's "Other Publications" section cites a scientific article titled "Adalimumab effectively reduces the signs and symptoms of active ankylosing spondylitis in patients with total spinal ankylosis," which may suggest the term refers to a clinically recognized patient group (’975 Patent, p. 1).
    • Evidence for a Narrower Interpretation: The absence of a specific definition in the patent could lead a party to argue that the term is indefinite or should be narrowly construed to cover only the most severe and unambiguous clinical presentations of AS, potentially limiting the scope of patients whose treatment would constitute direct infringement.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges that once Alvotech's aBLA is approved, its commercial activities will actively induce and contribute to infringement by others (Compl. ¶¶88, 99, 112, 125). The basis for this allegation is the confidential information provided by Alvotech regarding the "indications, dosage, and methods of use" for the AVT02 product, which presumably will be reflected in its product labeling and physician instructions (Compl. ¶¶99, 112, 115, 125).
  • Willful Infringement: Willfulness is alleged for all four patents-in-suit. The complaint asserts that Alvotech has knowledge of the patents due to AbbVie’s disclosures under the BPCIA process and the filing of the complaint itself, and that Alvotech "is aware, has knowledge, and/or is willfully blind" to the fact that its product and its formulation will infringe (Compl. ¶¶89-90, 101-103, 114-116, 126-127).

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

  • A central issue will be one of technical scope: Does the specific formulation of Alvotech's AVT02 product, as detailed in its confidential aBLA, meet the claimed parameters for properties like conductivity and the absence of buffers, particularly in light of the ambiguity introduced by claim terms such as "about"?
  • A key evidentiary question will be one of induced infringement: Will Alvotech's final, FDA-approved product label direct medical professionals to administer AVT02 to a patient population (e.g., those with "total spinal ankylosis") and according to a dosing regimen (e.g., a "multiple-variable dose") that falls squarely within the scope of AbbVie's method-of-use patents?
  • A procedural question will be the strategic significance of bifurcation: How will the defendant’s choice to litigate only four of the sixty-two patents identified by the plaintiff impact the overall dispute, and what influence might the prior successful IPR defenses of two of the asserted patent families have on litigation and settlement strategy?