DCT

1:16-cv-00221

Morphosys AG v. Janssen Biotech Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:16-cv-00221, D. Del., 10/11/2017
  • Venue Allegations: Plaintiff alleges venue is proper in the District of Delaware because Defendants have placed infringing products into the stream of commerce with the knowledge that they would be sold and used in the district.
  • Core Dispute: Plaintiff alleges that Defendants’ therapeutic antibody, Darzalex (daratumumab), for the treatment of multiple myeloma, infringes three patents related to human anti-CD38 antibodies.
  • Technical Context: The technology concerns fully human monoclonal antibodies that target the CD38 protein, a validated therapeutic target expressed on the surface of certain cancerous blood cells, particularly in multiple myeloma.
  • Key Procedural History: The complaint alleges that Defendants were aware of the lead patent since at least 2011, prior to its issuance, and conducted due diligence on it. It also notes that both Janssen and Genmab filed European Oppositions in January 2016 against the European counterpart to the lead U.S. patent, which may suggest prior art or invalidity arguments that could be raised in this litigation.

Case Timeline

Date Event
2004-02-06 Earliest Priority Date for ’746, ’061, and ’590 Patents
2012-08-01 Genmab and Janssen enter into license and collaboration agreement for Darzalex
2012-09-11 U.S. Patent No. 8,263,746 Issues
2015-11-16 FDA approves Darzalex for treatment of multiple myeloma
2015-12-01 U.S. Patent No. 9,200,061 Issues
2017-09-12 U.S. Patent No. 9,758,590 Issues
2017-10-11 Plaintiff files Second Amended Complaint

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

U.S. Patent No. 8,263,746 - "Anti-CD38 Human Antibodies and Uses Thereof"

The Invention Explained

  • Problem Addressed: The patent’s background section describes the need for therapeutic antibodies targeting the CD38 protein, which is over-expressed on malignant cells in hematological diseases like multiple myeloma. It notes that prior antibodies were often murine (mouse-derived), making them unsuitable for human administration, and that a need existed for fully human antibodies with high affinity and high efficacy in killing CD38-expressing cells (ʼ746 Patent, col. 1:41-2:32).
  • The Patented Solution: The invention provides fully human antibodies and their fragments that specifically bind to the CD38 protein. These antibodies are described as being capable of mediating the killing of CD38-positive target cells through immunological mechanisms like antibody-dependent cellular cytotoxicity (ADCC) and/or complement-dependent cytotoxicity (CDC) (ʼ746 Patent, Abstract; col. 2:43-54).
  • Technical Importance: The development of fully human antibodies was a significant step in antibody therapeutics, as it aimed to reduce the immunogenicity problems associated with earlier murine or chimeric antibodies, potentially allowing for safer and more effective long-term treatment of chronic diseases like cancer (ʼ746 Patent, col. 2:14-19).

Key Claims at a Glance

  • The complaint asserts infringement of one or more claims, referencing claims 1, 8, and 14 (Compl. ¶39, 40). Independent claim 1 is central.
  • Claim 1 Elements:
    • An isolated human antibody or functional fragment thereof,
    • which is capable of binding to an epitope of human CD38,
    • wherein said antibody or functional fragment thereof is capable of mediating killing of a CD38+ cell by ADCC and/or CDC.
  • The complaint generally alleges infringement of one or more claims, implicitly reserving the right to assert other claims, including dependent claims (Compl. ¶68).

U.S. Patent No. 9,200,061 - "Generation and Profiling of Fully Human HuCAL Gold®-Derived Therapeutic Antibodies Specific for Human CD3[8]"

The Invention Explained

  • Problem Addressed: This patent, from the same family as the ’746 patent, addresses the challenge of identifying human antibodies that bind to specific, therapeutically relevant regions (epitopes) of a target protein. It seeks to move beyond general binding to define antibodies by the precise location of their interaction with the target (ʼ061 Patent, col. 1:14-2:46).
  • The Patented Solution: The invention provides a method of treating hematologic cancers by administering a human anti-CD38 antibody that binds to a specific epitope region on the CD38 protein. Specifically, the patent claims a method using an antibody that binds to a region defined by amino acid residues 192-206 of the human CD38 protein sequence (ʼ061 Patent, Abstract; col. 2:47-3:44).
  • Technical Importance: By identifying a specific binding region, the invention provides a more precise definition for a therapeutic antibody, which can be critical for ensuring consistent biological activity and for distinguishing a novel therapeutic from existing antibodies that may bind to different parts of the same target protein (ʼ061 Patent, col. 27:45-54).

Key Claims at a Glance

  • The complaint asserts infringement of one or more claims, specifically referencing claim 1 (Compl. ¶41, 42, 43).
  • Claim 1 Elements:
    • A method of treating a hematologic cancer associated with the presence of CD38+ cells in a subject,
    • comprising administering to the subject an anti-CD38 antibody,
    • that binds an epitope of CD38 that contains one or more amino acid residues within 192-206 of human CD38 set forth as SEQ ID NO:22.
  • The complaint implicitly reserves the right to assert other claims (Compl. ¶87, 88).

U.S. Patent No. 9,758,590 - "Anti-CD38 Human Antibodies and Uses Thereof"

Technology Synopsis

  • This patent claims specific anti-CD38 antibody compositions, defined by their precise amino acid sequences, including the framework regions and the six complementarity determining regions (CDRs) that are primarily responsible for antigen binding. The claimed antibody has a specific VH3 heavy chain and kappa light chain structure (ʼ590 Patent, col. 27:55-28:21).

Asserted Claims & Accused Features

  • Asserted Claims: The complaint asserts at least Claim 1 (Compl. ¶137).
  • Accused Features: Plaintiff alleges that Darzalex is an anti-CD38 antibody that contains a framework sequence, a VH3 heavy chain, a kappa light chain, an IgG1 constant region, and six CDRs that meet all the limitations of claim 1 of the ’590 Patent (Compl. ¶45).

III. The Accused Instrumentality

Product Identification

  • The accused product is the therapeutic antibody Darzalex (daratumumab) (Compl. ¶6).

Functionality and Market Context

  • Darzalex is alleged to be a human anti-CD38 monoclonal antibody developed by Defendant Genmab and commercialized through a license with Defendant Janssen (Compl. ¶26, 29). It is indicated for the treatment of patients with multiple myeloma, a type of hematologic cancer (Compl. ¶27). The complaint alleges that Darzalex functions by binding to the CD38 protein on cancer cells and mediating their killing (Compl. ¶39).
  • The complaint highlights the product's commercial importance through its FDA approval and the substantial financial terms of the licensing agreement between Genmab and Janssen, which included a $55 million upfront payment and a $45 million payment for the first U.S. sale (Compl. ¶30, 31).

IV. Analysis of Infringement Allegations

’746 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
An isolated human antibody or functional fragment thereof, Darzalex is alleged to be a human CD38-directed monoclonal antibody. ¶64 col. 2:33-35
which is capable of binding to an epitope of human CD38, Darzalex is alleged to contain an antibody-binding region that specifically binds to CD38 at least within amino acids 44 to 206. ¶40 col. 3:20-24
wherein said antibody or functional fragment thereof is capable of mediating killing of a CD38+ cell by ADCC and/or CDC. Darzalex is reported to have efficacy in killing CD38 expressing cells and mediates killing of a CD38+ target cell. ¶39 col. 2:43-54

Identified Points of Contention

  • Scope Questions: Claim 1 is defined by functional capabilities ("capable of binding," "capable of mediating killing"). A central question will be whether the scope of these functional limitations is sufficiently supported by the patent's specification to be considered valid and enabled.
  • Technical Questions: The dispute may turn on the degree and type of cell "killing" mediated by Darzalex. The parties may contest whether Darzalex's mechanism of action falls squarely within the definitions of ADCC and/or CDC as understood in the art and described in the patent.

’061 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method of treating a hematologic cancer associated with the presence of CD38+ cells in a subject, Defendants are alleged to administer, and direct others to administer, Darzalex to treat multiple myeloma, a hematologic cancer. ¶42, 43 col. 27:47-50
comprising administering to the subject an anti-CD38 antibody Darzalex is alleged to be an anti-CD38 antibody. ¶27 col. 27:50-51
that binds an epitope of CD38 that contains one or more amino acid residues within 192-206 of human CD38... The complaint alleges that Darzalex "binds an epitope of CD38 that contains one or more amino acid residues within 192-206." This allegation is supported by a visual from a Genmab presentation indicating that amino acid D202 is essential for binding (Compl. p. 9). ¶41 col. 3:31-33

Identified Points of Contention

  • Evidentiary Questions: The key dispute will be factual and evidentiary: does Darzalex actually bind to an epitope containing one or more residues within the specific 192-206 amino acid window? The visual evidence provided in the complaint, which depicts a diagram titled "Daratumumab epitope Mapped on CD38 structure" and states "Amino acids D202...are essential for daratumumab binding," will be a central piece of evidence for the Plaintiff (Compl. p. 9).
  • Scope Questions: A potential issue is the interpretation of "binds an epitope...that contains one or more amino acid residues within 192-206." This raises the question of whether incidental contact is sufficient, or if a residue within this range must be a critical binding determinant.

V. Key Claim Terms for Construction

’746 Patent, Claim 1

  • The Term: "mediating killing of a CD38+ cell"
  • Context and Importance: This functional language is the core of claim 1. The definition of what constitutes "mediating killing" by ADCC and/or CDC, including the required level of efficacy, will be critical to determining both infringement and validity.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The claim language "ADCC and/or CDC" suggests that either mechanism is sufficient. The specification describes these as known mechanisms of action for therapeutic antibodies generally, which may support a construction encompassing standard industry understandings of these terms (ʼ746 Patent, col. 2:43-54).
    • Evidence for a Narrower Interpretation: The specification provides specific experimental examples (Examples 2 and 9) demonstrating ADCC and CDC activity for its exemplary antibodies. A defendant may argue that the term should be limited to the types or levels of killing demonstrated in those specific embodiments (ʼ746 Patent, col. 21:12-24:14).

’061 Patent, Claim 1

  • The Term: "binds an epitope of CD38 that contains one or more amino acid residues within 192-206"
  • Context and Importance: This limitation defines the invention by a specific structural interaction rather than by function alone. The entire infringement case for this patent hinges on proving that Darzalex meets this precise binding requirement. Practitioners may focus on this term because it is the primary point of distinction over prior art that might bind to other regions of CD38.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The phrase "contains one or more" could be argued to mean that if any part of the binding site (epitope) includes any single amino acid from the 192-206 range, the claim is met, even if other residues outside this range are also critical for binding.
    • Evidence for a Narrower Interpretation: The patent’s Figure 7, titled "Schematic Overview of Epitopes," specifically identifies the 192-206 region as the "Linear epitope" for the "MOR03079" antibody. This specific example may be used to argue that the term requires binding to this region as the primary determinant of specificity, not just incidental contact (ʼ746 Patent, Fig. 7). (Note: The '061 patent incorporates the '746 patent specification by reference).

VI. Other Allegations

  • Indirect Infringement: The complaint alleges inducement and contributory infringement for the method claims of the ’061 Patent. The basis is that Defendants' FDA-approved indication, marketing materials, and instructions for Darzalex encourage and instruct physicians to administer the drug for treating multiple myeloma, which allegedly constitutes direct infringement of the claimed method (Compl. ¶63, 65, 89).
  • Willful Infringement: The complaint alleges willful infringement for all three patents. For the ’746 Patent, willfulness is based on alleged pre-suit knowledge dating back to at least 2011, citing a public statement by Genmab's CEO and extensive due diligence by Janssen (Compl. ¶47, 50, 51). For the ’061 and ’590 Patents, willfulness is based on knowledge as of their respective issue dates, with continued infringing conduct thereafter (Compl. ¶52-55, 70, 75).

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

  • A core issue will be one of evidentiary proof: can Plaintiff produce sufficient technical evidence, beyond the preliminary diagram included in the complaint, to demonstrate that Darzalex binds to the specific 192-206 amino acid epitope required by the ’061 patent, and possesses the exact amino acid sequences claimed in the ’590 patent?
  • A second key question will be one of claim scope and validity: for the functionally claimed '746 patent, what level of efficacy is required to meet the "capable of mediating killing" limitation, and is that scope enabled and properly described by the patent's specification, particularly in light of the state of the art at the time of invention?
  • A third issue will be willfulness and damages: given the allegation that Defendants knew of and studied the ’746 patent family for years before launching their product, the question of whether their conduct was objectively reckless will be central to any potential enhancement of damages.