DCT

1:20-cv-01226

Regenxbio Inc v. Sarepta Therap Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:20-cv-01226, D. Del., 09/15/2020
  • Venue Allegations: Venue is alleged to be proper in the District of Delaware because both Defendant entities are organized under the laws of Delaware, and the court is alleged to have personal jurisdiction over them.
  • Core Dispute: Plaintiffs allege that Defendants' manufacture and use of a cultured host cell technology to produce recombinant adeno-associated virus (AAV) gene therapy products infringes a patent covering such host cells.
  • Technical Context: The dispute is in the field of gene therapy, which uses viral vectors—in this case, AAVs—to deliver therapeutic genes into a patient's cells to treat genetic diseases like muscular dystrophy.
  • Key Procedural History: The complaint details a chain of licensing rights for the patent-in-suit, originating with the University of Pennsylvania, licensed exclusively to GlaxoSmithKline LLC (GSK), which in turn provided an exclusive license to REGENXBIO. The complaint also alleges that GSK assigned to REGENXBIO any claims arising from Sarepta's infringement.

Case Timeline

Date Event
2001-11-13 ’617 Patent Priority Date
2002-05-31 University of Pennsylvania grants license to GSK
2009-02-24 University of Pennsylvania grants license to REGENXBIO
2009-03-06 GSK grants license to REGENXBIO
2020-01-07 U.S. Patent No. 10,526,617 Issues
2020-09-15 Complaint Filed

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

U.S. Patent No. 10,526,617 - Method of Detecting and/or Identifying Adeno-Associated Virus (AAV) Sequences and Isolating Novel Sequences Identified Thereby

  • Patent Identification: U.S. Patent No. 10,526,617, issued January 7, 2020.

The Invention Explained

  • Problem Addressed: The patent addresses the need to identify new AAV serotypes for use in gene therapy, particularly from non-human primate (NHP) tissues, to create gene delivery vectors with desirable properties. (’617 Patent, col. 1:44-52).
  • The Patented Solution: The invention provides novel AAV sequences isolated from NHP tissues, such as the AAVrh.10 serotype, and claims the tools used to produce them. The asserted claim is directed not to the final vector or therapy, but to the engineered "cultured host cell" that contains a recombinant nucleic acid molecule encoding the key viral protein (the capsid) and a therapeutic gene (a heterologous sequence). (’617 Patent, Abstract; col. 25:1-20). This cell acts as a factory for producing the AAV vectors.
  • Technical Importance: The development of novel AAV serotypes with distinct tissue tropisms (the ability to target specific cell types) was a critical advancement for making gene therapy safer and more effective for a variety of diseases. (’617 Patent, col. 26:7-16).

Key Claims at a Glance

  • The complaint asserts independent claim 1. (Compl. ¶27).
  • The essential elements of Claim 1 are:
    • A cultured host cell
    • containing a recombinant nucleic acid molecule
    • encoding an AAV vp1 capsid protein having a sequence comprising amino acids 1 to 738 of SEQ ID NO: 81 (AAVrh.10) OR a sequence at least 95% identical to the full length of amino acids 1 to 738 of SEQ ID NO: 81,
    • wherein the recombinant nucleic acid molecule further comprises a heterologous non-AAV sequence.
  • The complaint does not explicitly reserve the right to assert dependent claims.

III. The Accused Instrumentality

Product Identification

  • The directly accused instrumentality is the "cultured host cell technology" allegedly made and used by Defendants in the United States to produce their gene therapy products. (Compl. ¶¶ 1, 26, 28). The end products created using this technology are identified as SRP-9001, for treating Duchenne muscular dystrophy (DMD), and SRP-9003, for treating Limb-girdle muscular dystrophy (LGMD). (Compl. ¶1).

Functionality and Market Context

  • The complaint alleges that Defendants' process for producing SRP-9001 and SRP-9003 involves using cultured host cells containing a recombinant nucleic acid. (Compl. ¶¶ 28, 30). This nucleic acid allegedly encodes an AAVrh74 capsid protein, which is used to package and deliver a therapeutic transgene. (Compl. ¶29). These products are described as being in clinical development. (Compl. ¶35).

IV. Analysis of Infringement Allegations

No probative visual evidence provided in complaint.

’617 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A cultured host cell Defendants make and use cultured host cells in the United States to produce their gene therapy products. ¶¶ 28, 30 col. 25:3-20
containing a recombinant nucleic acid molecule The host cells contain a recombinant nucleic acid molecule used to produce AAV gene therapy products. ¶¶ 28, 30 col. 3:51-56
encoding an AAV vp1 capsid protein having a sequence comprising amino acids 1 to 738 of SEQ ID NO: 81 (AAVrh.10) or a sequence at least 95% identical to the full length of amino acids 1 to 738 of SEQ ID NO: 81 The accused host cells encode an AAVrh74 capsid protein, which allegedly has a sequence that is at least 95% identical (specifically, 99% identical) to the AAVrh.10 capsid protein of SEQ ID NO: 81. ¶29 col. 4:28-56
wherein the recombinant nucleic acid molecule further comprises a heterologous non-AAV sequence. The recombinant nucleic acid molecule allegedly contains a transgene (e.g., for micro-dystrophin) which constitutes a heterologous non-AAV sequence. ¶¶ 29, 30 col. 3:56-59

Identified Points of Contention

  • Scope Questions: The central dispute may turn on the scope of "a sequence at least 95% identical to...SEQ ID NO: 81." While the complaint alleges 99% identity between the accused AAVrh74 and the claimed AAVrh.10, the defense may challenge the validity of a claim defined by a percentage identity range, potentially raising issues of written description or enablement under 35 U.S.C. § 112.
  • Technical Questions: A primary factual question will be whether the AAVrh74 capsid protein sequence used by Sarepta is, in fact, at least 95% identical to SEQ ID NO: 81, according to the calculation methods described in the patent specification. The complaint cites an external document to support this, but this will be a key subject of discovery and expert analysis. (Compl. ¶29).

V. Key Claim Terms for Construction

  • The Term: "a sequence at least 95% identical"

    • Context and Importance: This term is the lynchpin of the infringement allegation. The accused product uses the AAVrh74 serotype, not the explicitly recited AAVrh.10 (SEQ ID NO: 81). Therefore, infringement can only be found if AAVrh74 falls within the "at least 95% identical" range. Practitioners may focus on this term because its construction, including the specific algorithm and parameters for calculating identity, will be dispositive.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The claim language itself, by including a percentage range rather than only the exact sequence, suggests an intent to cover variants beyond the specific embodiment of SEQ ID NO: 81. The specification supports this by stating the invention includes "variants," "fragments," and "modifications." (’617 Patent, col. 13:5-15).
      • Evidence for a Narrower Interpretation: The patent provides a detailed definition for calculating "percent sequence identity," referencing specific computer programs (e.g., FASTA) and default parameters. (’617 Patent, col. 4:28-56). A party could argue that this specific definition strictly cabins the scope and that any deviation from this prescribed method of comparison is improper.

  • The Term: "heterologous non-AAV sequence"

    • Context and Importance: This term is required to be part of the same nucleic acid molecule as the capsid-encoding sequence. The infringement theory depends on the therapeutic transgene (e.g., micro-dystrophin) meeting this definition.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The patent specification provides a broad definition, stating a heterologous sequence can be from a different species or simply a different gene from the same species. (’617 Patent, col. 17:15-18). It explicitly gives "transgenes" as an example of a sequence that can be delivered by the vectors. (Compl. ¶17; ’617 Patent, col. 19:6-21). This appears to directly support the plaintiff’s theory.
      • Evidence for a Narrower Interpretation: It could be argued that the term requires a sequence that is functionally and structurally distinct from any viral element. However, the specification's explicit inclusion of transgenes as part of the delivered genetic material makes a significantly narrower construction challenging based on the intrinsic evidence.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges both inducement and contributory infringement. The inducement allegation is based on Sarepta allegedly instructing and contracting with third-party contract manufacturing organizations (CMOs) to perform the infringing acts of making and using the claimed host cells. (Compl. ¶31). The contributory infringement allegation is based on Sarepta allegedly supplying essential components, such as plasmids that encode the AAVrh74 capsid protein, that have no substantial non-infringing use. (Compl. ¶31).
  • Willful Infringement: The complaint alleges that Sarepta became aware of the ’617 Patent no later than the filing date of the complaint and that any subsequent infringement is therefore willful. (Compl. ¶32). It also makes a more general allegation that Sarepta "knew or should have known" its actions constituted infringement, but provides no specific facts supporting pre-suit knowledge. (Compl. ¶33).

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

  • A central issue will be one of factual proof and claim scope: Can Plaintiffs prove through discovery that the AAVrh74 capsid sequence used by Sarepta is, in fact, "at least 95% identical" to the claimed AAVrh.10 sequence? Correspondingly, the case may test the validity of claims defined by such a percentage identity, raising questions of whether the patent adequately describes and enables the full scope of that claimed range.
  • A second key question will relate to the character of infringement: Given Sarepta’s alleged use of CMOs, the court will need to determine if Sarepta's own activities in the U.S. rise to the level of direct infringement ("making" or "using" the patented cell), or if liability rests on theories of indirect infringement, which require showing that the CMOs are direct infringers and that Sarepta possessed the requisite knowledge and intent.