DCT

2:17-cv-06496

Juno Therap Inc v. Kite Pharma Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 2:17-cv-06496, C.D. Cal., 09/01/2017
  • Venue Allegations: Venue is asserted based on Defendant having committed alleged acts of infringement in the district and maintaining a regular and established place of business there.
  • Core Dispute: Plaintiffs allege that Defendant’s CAR-T cancer immunotherapy product, axicabtagene ciloleucel, infringes a patent directed to nucleic acids that encode a specific type of chimeric T cell receptor.
  • Technical Context: The lawsuit concerns Chimeric Antigen Receptor T-cell (CAR-T) therapy, a field of immunotherapy where a patient’s own immune cells (T-cells) are genetically engineered to recognize and kill cancer cells.
  • Key Procedural History: The complaint notes that Defendant Kite Pharma previously initiated an inter partes review (IPR) proceeding at the U.S. Patent and Trademark Office, seeking to invalidate all claims of the patent-in-suit. The Patent Trial and Appeal Board (PTAB) issued a Final Written Decision concluding that Kite had not shown any claim to be unpatentable. This history may give rise to an issue of IPR estoppel, potentially precluding Kite from raising certain invalidity arguments in this litigation.

Case Timeline

Date Event
2002-05-28 '190 Patent Priority Date
2008-11-04 '190 Patent Issue Date
2015-08-13 Defendant Kite files IPR petition against '190 Patent
2016-06-20 Defendant Kite opens new commercial manufacturing facility
2016-12-04 Defendant Kite initiates rolling BLA submission for KTE-C19
2016-12-16 PTAB issues Final Written Decision in IPR, upholding all claims
2017-03-31 Defendant Kite completes BLA submission for KTE-C19
2017-05-26 FDA accepts KTE-C19 BLA for priority review
2017-09-01 Complaint Filing Date

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

U.S. Patent No. 7,446,190 - "Nucleic Acids Encoding Chimeric T Cell Receptors"

The Invention Explained

  • Problem Addressed: The patent’s background section describes the challenge of creating effective cancer immunotherapies, noting that T-cells often fail to mount a robust attack against tumors ('190 Patent, col. 1:12-31). It explains that early-generation artificial T-cell receptors, while able to provide an initial activation signal ("signal 1"), often failed to provide a necessary secondary "co-stimulatory" signal ("signal 2"). The absence of this second signal could lead to a weak immune response or even T-cell anergy or apoptosis ('190 Patent, col. 2:48-58).
  • The Patented Solution: The invention is a nucleic acid polymer that encodes a single, multi-part chimeric T cell receptor (TCR). This engineered receptor combines three critical components into one molecule: a binding element (like an antibody fragment) to recognize a target on a cancer cell, the intracellular signaling domain of the CD3ζ chain to provide signal 1, and a co-stimulatory signaling domain from a protein like CD28 to provide signal 2 ('190 Patent, Abstract; col. 2:11-26). By integrating both essential signals into a single receptor, the invention aims to enable genetically engineered T-cells to mount a more potent and sustained attack against target cells ('190 Patent, col. 2:3-7).
  • Technical Importance: This integrated design sought to overcome a critical hurdle in T-cell therapy by making the engineered cell self-sufficient for activation, removing its dependence on a separate co-stimulatory signal that is often absent in the tumor microenvironment ('190 Patent, col. 6:46-54).

Key Claims at a Glance

  • The complaint asserts independent claim 1 and dependent claims 2-3, 5, 7-9, and 11 ('190 Patent, col. 25:27-26:17; Compl. ¶56).
  • Independent Claim 1 requires:
    • A nucleic acid polymer encoding a chimeric T cell receptor, said chimeric T cell receptor comprising
    • (a) a zeta chain portion comprising the intracellular domain of human CD3ζ chain,
    • (b) a costimulatory signaling region,
    • (c) a binding element that specifically interacts with a selected target,
    • wherein the costimulatory signaling region comprises the amino acid sequence encoded by SEQ ID NO:6.
  • The complaint notes that the incorporated Exhibit 31 is not a complete list of all infringing products or asserted claims (Compl. ¶58).

III. The Accused Instrumentality

Product Identification

The primary accused instrumentality is Defendant Kite's CAR-T therapy product known as KTE-C19 or by its generic name, axicabtagene ciloleucel ("axi-cel") (Compl. ¶19). The complaint also focuses on the retroviral vector used to manufacture KTE-C19, which contains the allegedly infringing nucleic acid polymer (Compl. ¶26, 57).

Functionality and Market Context

  • KTE-C19 is described as a therapy in which a patient’s T-cells are engineered to express a chimeric antigen receptor (CAR) that targets the CD19 protein, an antigen expressed on the surface of B-cell lymphomas and leukemias (Compl. ¶18). The engineered cells are then used to find and kill cancer cells bearing the CD19 target (Compl. ¶18).
  • The complaint alleges that Kite is engaged in pre-commercialization activities, including manufacturing and stockpiling the KTE-C19 vector, in anticipation of imminent FDA approval and launch (Compl. ¶36, 38). These activities are positioned as being for commercial purposes and thus outside the statutory "safe harbor" for activities related to seeking regulatory approval (Compl. ¶40).

IV. Analysis of Infringement Allegations

The complaint alleges that the KTE-C19 retroviral vector contains a nucleic acid polymer that infringes the ’190 Patent. A schematic of the KTE-C19 construct provided in the complaint depicts its key components: an scFv (FMC63) binding domain, a Hinge/Transmembrane region, 'Signal 2: CD28,' and 'Signal 1: CD3ζ' (Compl. p. 8).

’190 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A nucleic acid polymer encoding a chimeric T cell receptor... Defendant’s KTE-C19 product is made using a retroviral vector, which is a nucleic acid polymer that encodes a chimeric antigen receptor. ¶26 col. 10:11-14
(a) a zeta chain portion comprising the intracellular domain of human CD3ζ chain, The KTE-C19 vector allegedly encodes a TCR-zeta cytoplasmic region, which provides the primary activation signal (Signal 1). ¶9, ¶26 col. 11:9-16
(b) a costimulatory signaling region, ... wherein the costimulatory signaling region comprises the amino acid sequence encoded by SEQ ID NO:6. The KTE-C19 construct allegedly includes a CD28 costimulatory signaling region. The complaint alleges the vector encodes an amino acid sequence identical to that of SEQ ID NO:6. ¶13, ¶26 col. 11:20-27
(c) a binding element that specifically interacts with a selected target, The KTE-C19 construct allegedly uses an anti-CD19 scFv derived from the FMC63 mouse hybridoma as its binding element to target the CD19 antigen on cancer cells. ¶20, ¶26 col. 11:34-37

Identified Points of Contention

  • Scope Questions: The complaint dedicates significant attention to the 35 U.S.C. § 271(e)(1) "safe harbor," which exempts certain activities from infringement if they are reasonably related to seeking FDA approval. This suggests a primary legal dispute will be whether Defendant's alleged stockpiling of vectors for commercial launch falls outside the protection of this safe harbor (Compl. ¶34-40). This raises the question: Do Defendant's pre-approval manufacturing and supply chain activities constitute infringing commercial use, or are they protected activities "solely for uses reasonably related to the development and submission of information" to the FDA?
  • Technical Questions: The complaint alleges that the KTE-C19 vector encodes an amino acid sequence "identical" to the patent's SEQ ID NO:6 (Compl. ¶26). A key evidentiary question will be whether discovery confirms this allegation. If the sequences are not identical, the analysis may shift to whether any differences are insubstantial under the doctrine of equivalents.

V. Key Claim Terms for Construction

  • The Term: "costimulatory signaling region"
  • Context and Importance: This term is at the heart of the patent's purported advance over the prior art. Claim 1 defines this region by requiring it to comprise "the amino acid sequence encoded by SEQ ID NO:6." The construction of this term is critical because infringement hinges on the accused product containing this specific functional and structural element. Practitioners may focus on this term to determine whether any variation from the exact sequence of SEQ ID NO:6 could escape infringement.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The patent specification discloses that other costimulatory molecules, such as "4-1BB, DAP-10 and ICOS," are also "suitably employed in the invention," which could support an argument that the term functionally encompasses more than just the CD28-derived sequence ('190 Patent, col. 11:49-54).
    • Evidence for a Narrower Interpretation: Claim 1 itself explicitly ties the term to a specific structure by requiring it to comprise the sequence of SEQ ID NO:6 ('190 Patent, col. 25:37-38). An argument could be made that for this specific claim, the patentee defined the term by this express limitation, narrowing its scope to that particular amino acid sequence or one that contains it.

VI. Other Allegations

Indirect Infringement

The complaint alleges induced infringement (§ 271(b)), asserting that Defendant knowingly encourages and assists partner institutions and end-users to directly infringe the ’190 Patent (Compl. ¶61). It also pleads contributory infringement (§ 271(c)), alleging the KTE-C19 product is a material part of the invention, especially made for infringement, and not a staple article of commerce (Compl. ¶62).

Willful Infringement

The complaint alleges willful infringement based on Defendant's pre-suit knowledge of the ’190 Patent. It cites Defendant's own filing of an IPR petition against the patent on August 13, 2015, as direct evidence of this knowledge (Compl. ¶65, ¶68). The complaint argues that Defendant's continued activities in the face of this knowledge, particularly after the PTAB upheld the patent's claims, demonstrates deliberate infringement (Compl. ¶68).

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

  • A central legal issue will be one of statutory scope: are the Defendant's alleged pre-approval manufacturing and stockpiling of the accused KTE-C19 vector acts of commercial preparation that fall outside the § 271(e)(1) safe harbor, or are they activities "reasonably related" to seeking FDA approval and therefore shielded from infringement liability?
  • A key question regarding damages will be one of willfulness: does the Defendant’s decision to proceed toward commercialization of its KTE-C19 product, after its own IPR challenge to the ’190 Patent was rejected by the PTAB, constitute objective recklessness that would support a finding of willful infringement?
  • A core evidentiary question will be one of technical identity: will discovery confirm the complaint's allegation that the nucleic acid in Defendant's KTE-C19 vector encodes a costimulatory signaling region with an amino acid sequence identical to the patent's SEQ ID NO:6, thereby simplifying the literal infringement analysis?