DCT

4:10-cv-40004

Centocor Ortho BIOTECH, INC. v. Abbott GmbH & CO., KG

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 4:10-cv-40004, D.D.C., 08/28/2009
  • Venue Allegations: Venue is alleged to be proper under 28 U.S.C. § 1391.
  • Core Dispute: Plaintiff Centocor seeks a declaratory judgment that its product STELARA does not infringe and/or that two of Defendant Abbott's patents are invalid.
  • Technical Context: The technology concerns human monoclonal antibodies designed to bind to and neutralize human interleukin-12 (IL-12), a protein involved in inflammatory and autoimmune conditions such as psoriasis.
  • Key Procedural History: This action for declaratory judgment was filed in response to a patent infringement complaint filed by Abbott against Centocor on August 10, 2009, in the District of Massachusetts. The complaint also notes that the '128 patent was previously the subject of Patent Interference No. 105,592, a proceeding at the U.S. Patent and Trademark Office to determine priority of invention, which may be relevant to the patent’s validity.

Case Timeline

Date Event
1999-03-25 Priority Date for U.S. Patent Nos. 6,914,128 and 7,504,485
2005-07-05 U.S. Patent No. 6,914,128 Issues
2009-03-17 U.S. Patent No. 7,504,485 Issues
2009-08-10 Abbott files initial infringement complaint against Centocor in D. Mass.
2009-08-28 Centocor files this Complaint for Declaratory Judgment

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

U.S. Patent No. 6,914,128 - "HUMAN ANTIBODIES THAT BIND HUMAN IL-12 AND METHODS FOR PRODUCING"

  • Patent Identification: U.S. Patent No. 6,914,128, titled "HUMAN ANTIBODIES THAT BIND HUMAN IL-12 AND METHODS FOR PRODUCING," issued on July 5, 2005 (’128 Patent).

The Invention Explained

  • Problem Addressed: The patent describes Interleukin-12 (IL-12) as a cytokine that plays a critical role in mediating autoimmune and inflammatory diseases (e.g., psoriasis, Crohn's disease, multiple sclerosis) (’128 Patent, col. 1:45-50, 74:29-57). It notes that therapeutic antibodies derived from non-human sources (like mice) can trigger an undesirable "human anti-mouse antibody" (HAMA) immune response in patients, limiting their effectiveness for long-term treatment (’128 Patent, col. 2:30-45).
  • The Patented Solution: The invention provides "isolated human antibodies" that specifically bind to human IL-12 and neutralize its activity (’128 Patent, Abstract). By using antibody sequences that correspond to human germline sequences, the invention aims to create a therapeutic that is less likely to be rejected by the patient's immune system, allowing for safer and more prolonged treatment courses (’128 Patent, col. 2:45-55; col. 26:55-65).
  • Technical Importance: The development of fully human antibodies represented a significant advance over earlier chimeric or murine antibodies by reducing the risk of immunogenicity in patients undergoing chronic therapy for autoimmune disorders (’128 Patent, col. 2:30-45).

Key Claims at a Glance

  • The complaint seeks a declaratory judgment of non-infringement of any and all claims of the patent (Compl. ¶16). Independent claim 1 is representative of the antibody claims.
  • Independent Claim 1:
    • An isolated human antibody, or an antigen-binding portion thereof, that binds to human IL-12
    • and dissociates from human IL-12 with a K_d of 1x10⁻⁹ M or less, as determined by surface plasmon resonance.

U.S. Patent No. 7,504,485 - "HUMAN ANTIBODIES THAT BIND HUMAN IL-12"

  • Patent Identification: U.S. Patent No. 7,504,485, titled "HUMAN ANTIBODIES THAT BIND HUMAN IL-12," issued on March 17, 2009 (’485 Patent).

The Invention Explained

  • Problem Addressed: As a divisional of the application that led to the ’128 Patent, the ’485 Patent addresses the same technical problem: the need for effective, non-immunogenic therapies for IL-12-mediated autoimmune and inflammatory disorders (’485 Patent, col. 1:45-50; col. 2:26-46).
  • The Patented Solution: The ’485 Patent claims pharmaceutical compositions that contain the isolated human anti-IL-12 antibody (’485 Patent, Abstract). The claims are directed not just to the antibody itself, but to its formulation for therapeutic use, specifically claiming compositions that include the antibody and an additional agent, and which bind to a specific subunit (p40) of the IL-12 protein (’485 Patent, col. 2:50-55, Claim 1).
  • Technical Importance: This patent extends the protection from the antibody molecule itself to the formulated drug product, which is the form administered to patients for treating diseases like plaque psoriasis (’485 Patent, col. 2:55-65).

Key Claims at a Glance

  • The complaint seeks a declaratory judgment of non-infringement of any and all claims of the patent (Compl. ¶20). Independent claim 1 is a representative composition claim.
  • Independent Claim 1:
    • A pharmaceutical composition comprising an isolated human antibody, or an antigen-binding portion thereof, which is capable of binding to an epitope of the p40 subunit of human IL-12, wherein the antibody or antigen binding portion thereof, neutralizes a biological activity of the first heterodimer and the second heterodimer,
    • and further comprising an additional agent.

III. The Accused Instrumentality

Product Identification

  • The accused instrumentality is Centocor's product STELARA®, the brand name for the antibody ustekinumab (Compl. ¶12).

Functionality and Market Context

  • The complaint identifies STELARA as a biologic drug for treating adults with moderate-to-severe plaque psoriasis (Compl. ¶12). Its active ingredient is ustekinumab, which the complaint describes as an "IL-12 antibody" (Compl. ¶12). The complaint notes that STELARA is the "first in a new class of biologics" for this treatment, suggesting it represents a significant commercial product (Compl. ¶12).

IV. Analysis of Infringement Allegations

The complaint is for declaratory judgment and does not contain detailed infringement allegations or claim charts. It states that Abbott's prior lawsuit alleged that Centocor's "making, using, offering for sale and/or selling" of STELARA infringed the ’128 and ’485 patents (Compl. ¶12). The complaint does not provide sufficient detail for a full claim-chart analysis.

Identified Points of Contention:
Based on the claims and the nature of the accused product, the infringement analysis raises several questions:

  • For the ’128 Patent:

    • Scope Question: Does the antibody ustekinumab meet the definition of an "isolated human antibody" as that term is used in the patent? The patent defines this based on correspondence to human germline immunoglobulin sequences (’128 Patent, col. 26:55-65). The resolution may depend on the specific amino acid sequence of ustekinumab and how the court construes the required degree of "correspondence."
    • Technical Question: Does ustekinumab dissociate from human IL-12 with a dissociation constant (K_d) of 1x10⁻⁹ M or less? Evidence regarding the binding affinity of STELARA, and whether it is measured "by surface plasmon resonance" as required by the claim, will be a central factual issue.

  • For the ’485 Patent:

    • Scope Question: A primary question is whether the STELARA product, as formulated, is a "pharmaceutical composition" that comprises an "additional agent" beyond the ustekinumab antibody itself. The interpretation of "additional agent" will be critical.
    • Technical Question: Does ustekinumab bind to "an epitope of the p40 subunit of human IL-12" as claimed? While the complaint identifies STELARA as an "IL-12 antibody," it does not specify the binding site, which is a required limitation of claim 1 of the ’485 patent (Compl. ¶12; ’485 Patent, col. 381:42-45).

V. Key Claim Terms for Construction

  • Term: "isolated human antibody" (’128 Patent, Claim 1)

    • Context and Importance: This term is the foundation of the asserted product claims. Its construction will determine whether Centocor's ustekinumab, a therapeutic monoclonal antibody, falls within the scope of the claims. Practitioners may focus on this term because the degree of "humanness" required could be a point of dispute.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The specification defines "human antibodies" as those "having variable and constant regions corresponding to human germline immunoglobulin sequences" (’128 Patent, col. 26:55-58). This language may support a construction covering any antibody derived from human genetic sequences, even with some modifications.
      • Evidence for a Narrower Interpretation: The specification heavily discusses specific antibody embodiments, such as "J695," which is derived from a "Joe 9 wild type" sequence and modified (’128 Patent, col. 30:65-31:25). A party could argue that the term should be limited to antibodies with a high degree of sequence identity to the disclosed examples or those made by the patent's disclosed methods, such as phage display.

  • Term: "additional agent" (’485 Patent, Claim 1)

    • Context and Importance: This term appears in a composition claim and is essential for infringement. If the STELARA drug product is found to contain only the ustekinumab antibody and inert excipients, it may not infringe claims requiring an "additional agent."
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The specification provides an extensive and non-limiting list of potential "additional agents," including broad categories such as "corticosteroids" and "non-steroidal anti-inflammatory drugs (NSAIDS)" (’485 Patent, col. 72:14-25). This could support an argument that the term covers any substance other than the antibody, including stabilizers or buffers present in the final formulation.
      • Evidence for a Narrower Interpretation: The specification introduces the concept in the context of "combination" therapies, stating the antibody "can also be used in combination with one or more other agents" for treating disorders (’485 Patent, col. 72:10-13). This language suggests the "additional agent" must be a therapeutically active substance intended to provide a synergistic or additive clinical effect, not merely an inert formulation excipient.

VI. Other Allegations

  • Indirect Infringement: Centocor seeks a declaratory judgment that it has not contributed to or induced infringement of the patents-in-suit (Compl. ¶15, ¶19). The complaint does not, however, detail the specific factual allegations of indirect infringement made by Abbott in the underlying Massachusetts litigation.
  • Willful Infringement: The complaint does not allege willful infringement. Instead, it asks the court to declare the case "exceptional" under 35 U.S.C. § 285 and award Centocor its attorneys' fees, a remedy available to a prevailing party in exceptional circumstances (Compl., Prayer for Relief ¶E). The factual basis for this request is not specified in the complaint.
  • Invalidity: Centocor alleges that one or more claims of the patents are invalid for failing to comply with 35 U.S.C. §§ 101, 102, 103, and/or 112 (Compl. ¶21, ¶24). The allegations cite failure to meet the requirements for novelty, non-obviousness, written description, and enablement, but are presented in boilerplate fashion without specific supporting facts, with the notable exception of the reference to the prior patent interference proceeding (Compl. ¶9).

No probative visual evidence provided in complaint.

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

This declaratory judgment action appears poised to center on three fundamental questions for the court:

  1. A core issue will be one of priority of invention: The complaint’s reference to Patent Interference No. 105,592 suggests a central dispute over which party was the first to invent the claimed human anti-IL-12 antibody. The outcome could determine the validity of Abbott's patents under 35 U.S.C. § 102(g).

  2. A key dispute will concern claim scope and construction: Can the term "isolated human antibody" be construed to cover Centocor’s STELARA product? Further, does the term "additional agent" in the ’485 patent require a second therapeutically active ingredient, or can it be satisfied by standard pharmaceutical excipients present in the final STELARA formulation?

  3. A significant validity challenge may relate to enablement and written description: Given that the patents claim human antibodies through both functional properties (e.g., binding affinity) and specific amino acid sequences, a key question will be whether the patent specifications adequately describe and enable the full breadth of the claimed genus of antibodies, or if the claims are invalid for overreaching beyond the specific examples disclosed.