DCT
3:18-cv-12668
AbbVie Inc v. Sandoz Inc
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: AbbVie Inc. (Delaware) and AbbVie Biotechnology Ltd (Bermuda)
- Defendant: Sandoz Inc. (Colorado), Sandoz GmbH (Austria), and Sandoz International GmbH (Germany)
- Plaintiff’s Counsel: McCarter & English, LLP
- Case Identification: 3:18-cv-12668, D.N.J., 08/10/2018
- Venue Allegations: Venue is alleged to be proper in the District of New Jersey because Defendant Sandoz Inc. has its principal place of business in the district and has agreed that New Jersey is an appropriate venue for this lawsuit.
- Core Dispute: Plaintiff alleges that Defendant’s proposed biosimilar adalimumab product, intended as a copy of Plaintiff's biologic drug HUMIRA®, infringes patents related to a specific dosing regimen and a stable, high-concentration formulation.
- Technical Context: The case concerns biologics, specifically fully human monoclonal antibodies that neutralize tumor necrosis factor-alpha (TNF-α) to treat inflammatory autoimmune diseases, a significant segment of the pharmaceutical market.
- Key Procedural History: The complaint was filed following pre-litigation information exchanges under the Biologics Price Competition and Innovation Act (BPCIA), during which Plaintiff identified 84 patents it believed could be asserted. The parties subsequently narrowed the scope of this initial lawsuit to two patents. The complaint also notes that the Patent Trial and Appeal Board (PTAB) previously rejected challenges by Sandoz in inter partes review (IPR) proceedings against related AbbVie patents, including one of the patents-in-suit.
Case Timeline
| Date | Event |
|---|---|
| 2002-08-16 | Priority Date for U.S. Patent No. 9,750,808 |
| 2004-04-09 | Priority Date for U.S. Patent No. 9,187,559 |
| 2015-11-17 | Issue Date for U.S. Patent No. 9,187,559 |
| 2017-09-05 | Issue Date for U.S. Patent No. 9,750,808 |
| 2018-01-16 | Sandoz aBLA for GP2017 accepted by FDA (on or before this date) |
| 2018-08-10 | Complaint Filing Date |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 9,187,559 - "Multiple-Variable Dose Regimen for Treating Idiopathic Inflammatory Bowel Disease"
The Invention Explained
- Problem Addressed: The patent describes a need for improved methods of treating TNFα-related disorders, such as Crohn's disease, where existing treatments "do not completely abate the inflammatory process and have significant side effects" (’559) Patent, col. 2:20-24).
- The Patented Solution: The invention proposes a "multiple-variable dose method" that begins with a higher "induction dose" to quickly achieve a therapeutic threshold level of the TNFα inhibitor in the body. This is followed by a lower "treatment dose" for maintenance, aiming to provide a more effective and safer therapeutic outcome than a constant-dose regimen. (’559 Patent, col. 2:31-41; Abstract).
- Technical Importance: This "loading dose" followed by "maintenance dose" approach is designed to establish and maintain therapeutic drug concentrations more rapidly and consistently than a flat dosing regimen, potentially leading to faster and more durable clinical remission. (’559 Patent, col. 11:66-12:5).
Key Claims at a Glance
- The complaint asserts infringement of claims 1-30 of the ’559 Patent (Compl. ¶100). Independent claim 1 is representative.
- Essential elements of Independent Claim 1:
- A multiple-variable dose method for treating idiopathic inflammatory bowel disease in a human subject.
- The method comprises subcutaneously administering adalimumab to the subject.
- A first dose of 160 mg is administered within a day.
- A second dose of 80 mg is administered within a day, two weeks after the first dose.
U.S. Patent No. 9,750,808 - "Formulation of Human Antibodies for Treating TNF-Alpha Associated Disorders"
The Invention Explained
- Problem Addressed: The patent addresses the need for a stable, liquid aqueous pharmaceutical formulation suitable for therapeutic use, particularly one with a high concentration of an antibody and an extended shelf life. (’808 Patent, col. 3:24-33).
- The Patented Solution: The patent discloses a specific formulation that includes a human anti-TNFα antibody (adalimumab, also known as D2E7) at a high concentration, combined with a specific buffer system and pH range (about 4 to 8). This combination is described as enhancing the stability of the antibody in a liquid form suitable for injection. (’808 Patent, Abstract; col. 13:14-53).
- Technical Importance: Creating a stable, high-concentration liquid formulation of a biologic drug allows for subcutaneous self-administration with a smaller injection volume, which improves patient convenience and compliance compared to intravenous infusions or formulations requiring lyophilization and reconstitution. (’808 Patent, col. 4:1-11).
Key Claims at a Glance
- The complaint asserts infringement of claims 1-10, 14-17, and 24-27 of the ’808 Patent (Compl. ¶113). Independent claim 1 is representative.
- Essential elements of Independent Claim 1:
- A stable liquid aqueous pharmaceutical formulation.
- It comprises a human anti-human TNFα IgG1 antibody (D2E7) at a concentration of 45 to 105 mg/ml.
- It includes a buffer system.
- The formulation is isotonic, suitable for single-use subcutaneous injection, and has a pH of 4 to 8.
III. The Accused Instrumentality
Product Identification
- The accused instrumentality is Sandoz's proposed biosimilar adalimumab product, identified as GP2017 (the "Sandoz aBLA Product") (Compl. ¶6, ¶19).
Functionality and Market Context
- Sandoz's product is a biosimilar version of AbbVie's HUMIRA®, meaning it is a biologic drug intended to have no clinically meaningful differences from HUMIRA® in terms of safety, purity, and potency (Compl. ¶6, ¶61, ¶75). Sandoz has submitted an abbreviated Biologics License Application ("aBLA") to the FDA seeking approval to market the product in the United States for indications for which HUMIRA® is approved (Compl. ¶76, ¶79). The complaint alleges that Sandoz’s aBLA includes a proposed package insert with directions for administration (Compl. ¶101).
- No probative visual evidence provided in complaint.
IV. Analysis of Infringement Allegations
The complaint bases its infringement allegations on confidential information Sandoz disclosed to AbbVie as part of the BPCIA process, which describes the proposed product's formulation and its intended methods of use (Compl. ¶99, ¶112).
Infringement Allegations: U.S. Patent No. 9,187,559
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A multiple-variable dose method for treating idiopathic inflammatory bowel disease in a human subject in need thereof, | Sandoz is seeking FDA approval to sell its aBLA Product for indications for which HUMIRA is approved, including inflammatory bowel diseases, and has a proposed package insert that allegedly instructs medical practitioners and patients on methods of use. | ¶98, ¶101 | col. 2:31-34 |
| comprising subcutaneously administering to the human subject: a first dose of 160 mg of adalimumab administered to the human subject within a day; | The proposed package insert for the Sandoz aBLA product allegedly instructs users to administer an initial subcutaneous dose of 160 mg. | ¶101 | col. 12:25-30 |
| and a second dose of 80 mg of adalimumab administered to the human subject within a day, wherein the second dose is administered two weeks following administration of the first dose. | The proposed package insert for the Sandoz aBLA product allegedly instructs users to administer a subsequent subcutaneous dose of 80 mg two weeks after the initial dose. | ¶101 | col. 12:25-30 |
Infringement Allegations: U.S. Patent No. 9,750,808
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A stable liquid aqueous pharmaceutical formulation | The Sandoz aBLA Product is alleged to be a stable liquid aqueous formulation. | ¶112, ¶113 | col. 7:42-53 |
| comprising: a human anti-human Tumor Necrosis Factor alpha (TNFα) IgG1 antibody at a concentration of 45 to 105 mg/ml, wherein the antibody is D2E7, and a buffer system; | Based on confidential information in the aBLA, the Sandoz product is alleged to contain the adalimumab (D2E7) antibody at a concentration within the claimed range and to contain a buffer system. | ¶99, ¶112 | col. 13:14-20 |
| wherein the formulation is isotonic, suitable for single-use subcutaneous injection, and has a pH of 4 to 8. | The Sandoz aBLA Product is allegedly formulated to be isotonic, for single-use subcutaneous injection, and to have a pH within the claimed range. | ¶99, ¶112 | col. 13:14-20 |
Identified Points of Contention
- Scope Questions: For the ’559 Patent, a central question will be whether the specific instructions for use in Sandoz's final, FDA-approved product label will direct or encourage administration according to the precise dosing amounts and schedule recited in the claims. The analysis will depend on the exact language of the label Sandoz seeks to market.
- Technical Questions: For the ’808 Patent, the dispute may turn on a direct factual comparison. The primary question is whether Sandoz’s GP2017 product formulation, as detailed in its confidential aBLA, meets every limitation of the asserted claims, including the specific antibody concentration, pH range, and the components of the buffer system as may be further defined in dependent claims.
V. Key Claim Terms for Construction
- The Term: "stable" (from Claim 1 of the ’808 Patent)
- Context and Importance: The term "stable" is a primary characteristic of the claimed formulation. Its definition is critical because infringement will depend on whether the accused product exhibits the claimed stability, which the patent links to specific physical and chemical properties. Practitioners may focus on this term because it is a term of degree that the patent itself seeks to define.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The preamble of claim 1 recites "A stable liquid aqueous pharmaceutical formulation," which could be argued to be a statement of intended use or result, rather than a strict limitation defined by the subsequent elements. This may support an interpretation where stability is a general quality achieved by, but not strictly limited to, the recited components.
- Evidence for a Narrower Interpretation: The specification provides detailed definitions, stating a "'stable' formulation is one in which the antibody therein essentially retains its physical stability and/or chemical stability and/or biological activity upon storage" (’808 Patent, col. 7:42-46). It further defines "physical stability" (no signs of aggregation, precipitation, or denaturation) and "chemical stability" (quantifying altered forms of the antibody), providing specific metrics that could be used to narrowly define what qualifies as "stable" under the patent. (’808 Patent, col. 7:54-67).
VI. Other Allegations
- Indirect Infringement: The complaint alleges induced infringement of the ’559 Patent on the basis that Sandoz’s proposed package insert will instruct medical practitioners and patients to perform the steps of the patented method (Compl. ¶100-101, ¶131-132). It alleges induced infringement of the ’808 Patent on the basis that Sandoz corporate entities will direct the manufacture of the allegedly infringing formulation (Compl. ¶114-116, ¶147-149).
- Willful Infringement: The complaint alleges that Sandoz has knowledge of the patents-in-suit due to AbbVie's disclosures made during the BPCIA patent exchange process and through the filing of the complaint itself. It further alleges that Sandoz is acting knowingly or with willful blindness, which forms the basis for a claim of willful infringement. (Compl. ¶103-104, ¶118-119, ¶133-135, ¶150-152).
VII. Analyst’s Conclusion: Key Questions for the Case
- A core issue will be one of induced infringement: For the ’559 method-of-use patent, will the specific language of Sandoz's final, FDA-approved package insert actively instruct or encourage medical professionals and patients to administer the biosimilar product using the exact two-step loading and maintenance dose regimen recited in the claims?
- A key evidentiary question will be one of compositional identity: For the ’808 formulation patent, does the Sandoz GP2017 product, as confidentially described in its regulatory filings, contain every element of the asserted claims, including the specific antibody concentration, pH range, and buffer components required by the patent?
- A central strategic question, framed by the BPCIA context, is how the resolution of this "first wave" litigation on two patents will influence the viability and timing of Sandoz’s market entry, given Plaintiff’s explicit reservation of rights to assert dozens of other patents in a potential "second wave" of litigation.