DCT

1:23-cv-00667

Regenxbio Inc v. Sarepta Therap Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:

  • Case Identification: 1:23-cv-00667, D. Del., 06/20/2023

  • Venue Allegations: Venue is asserted based on Defendants being incorporated in the State of Delaware and maintaining minimum contacts with the judicial district.

  • Core Dispute: Plaintiffs allege that Defendants' gene therapy product for Duchenne muscular dystrophy, SRP-9001, infringes a patent directed to engineered adeno-associated virus (AAV) vectors.

  • Technical Context: The lawsuit concerns engineered viral vectors used in gene therapy, a field focused on delivering therapeutic genes to treat genetic disorders by replacing or supplementing defective genes.

  • Key Procedural History: The complaint details a chain of licensing agreements establishing Plaintiffs' rights to the patent-in-suit, originating with The University of Pennsylvania and flowing through GlaxoSmithKline LLC to REGENXBIO. The lawsuit was filed on the same day the patent issued and alleges infringement based on Defendants' manufacture of SRP-9001 in anticipation of a commercial launch following expected FDA approval.

Case Timeline

Date Event
2002-05-31 University of Pennsylvania grants license to GlaxoSmithKline (GSK)
2005-04-07 ’274 Patent Priority Date
2009-02-24 University of Pennsylvania grants license to REGENXBIO
2009-03-06 GSK grants sublicense to REGENXBIO
2022-11-28 Sarepta submits Biologics License Application (BLA) to FDA for SRP-9001
2023-06-20 ’274 Patent Issues
2023-06-20 Complaint Filed

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

  • Patent Identification: U.S. Patent No. 11,680,274, "Method of Increasing the Function of an AAV Vector", issued on June 20, 2023.

The Invention Explained

  • Problem Addressed: The patent addresses the need for adeno-associated virus (AAV) vectors with improved or altered functions for use in gene therapy. Naturally occurring AAVs have limitations in their ability to efficiently deliver genes to specific target tissues or may be neutralized by the human immune system, hindering their therapeutic potential (’274 Patent, col. 1:49-62).
  • The Patented Solution: The invention provides engineered AAVs with modified capsid proteins. The method involves identifying specific amino acid positions ("singletons") in a parental AAV capsid sequence and altering them to create a new vector with enhanced characteristics, such as improved packaging efficiency or transduction of target cells (’274 Patent, col. 2:63-col. 3:5). The patent claims specific recombinant AAVs containing a capsid protein with a defined amino acid sequence, or a sequence highly identical to it, that includes a specific amino acid at a particular position (’274 Patent, col. 193:1-13).
  • Technical Importance: Engineering AAV capsids to have novel properties is a key strategy for developing safer and more effective gene therapies tailored to specific diseases and tissues (’274 Patent, col. 7:15-18).

Key Claims at a Glance

  • The complaint asserts infringement of at least independent Claim 1 (Compl. ¶31).
  • The essential elements of Claim 1 are:
    • A recombinant adeno-associated virus (AAV) comprising an AAV capsid and a minigene.
    • The minigene must have AAV inverted terminal repeats and a heterologous gene operably linked to regulatory sequences for expression in a host cell.
    • The AAV capsid must comprise AAV vp1, vp2, and vp3 proteins.
    • The AAV vp1 proteins must have an amino acid sequence that is either i) identical to SEQ ID NO: 4 (AAVrh46), or ii) at least 95% identical to SEQ ID NO: 4.
    • The amino acid residue corresponding to position 665 in SEQ ID NO: 4 must be an asparagine (N).
  • The complaint focuses its allegations on Claim 1 (Compl. ¶31, ¶32).

III. The Accused Instrumentality

Product Identification

  • The accused product is SRP-9001, an investigational gene therapy also known by the nonproprietary name delandistrogene moxeparvovec (Compl. ¶1, ¶33).

Functionality and Market Context

  • SRP-9001 is described as a gene therapy product designed to treat Duchenne muscular dystrophy (DMD) (Compl. ¶1). It allegedly uses an AAV vector to deliver a microdystrophin transgene, which is a shortened but functional version of the human dystrophin gene (Compl. ¶1, ¶33).
  • The complaint alleges that SRP-9001 uses an AAVrh74 capsid protein to package and deliver this transgene (Compl. ¶33). It further alleges that Sarepta has partnered with Catalent and Thermo Fisher Scientific for the manufacture of SRP-9001 and is building a commercial stock in anticipation of FDA approval and launch (Compl. ¶35, ¶36).

IV. Analysis of Infringement Allegations

No probative visual evidence provided in complaint.

’274 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A recombinant adeno-associated virus (AAV) comprising an AAV capsid and a minigene having AAV inverted terminal repeats and a heterologous gene operably linked to regulatory sequences which direct expression of the heterologous gene in a host cell... SRP-9001 is a recombinant AAV comprising a capsid and a minigene with a heterologous gene (microdystrophin) for expression in a host cell. ¶32 col. 11:1-10; col. 11:64-67
...wherein the AAV capsid comprises AAV vp1 proteins, AAV vp2 proteins, and AAV vp3 proteins... The SRP-9001 AAVrh74 vector has vp1, vp2, and vp3 capsid proteins. ¶33 col. 8:60-63
...wherein the AAV vp1 proteins have... an amino acid sequence at least 95% identical to the full length of amino acids 1 to 738 of SEQ ID NO: 4 (AAVrh46)... The vp1 capsid protein of the accused AAVrh74 vector allegedly has an amino acid sequence that is at least 95% identical to SEQ ID NO: 4. ¶33 col. 5:29-32
...wherein the amino acid residue corresponding to position 665 in SEQ ID NO: 4 is N when aligned along the full length of amino acids 1 to 738 of SEQ ID NO: 4. The amino acid residue at the position corresponding to 665 in SEQ ID NO: 4 is allegedly N in the accused product. ¶33 col. 3:10-18

Identified Points of Contention

  • Scope Questions: The central dispute may turn on whether the accused AAVrh74 capsid falls within the claimed scope. This raises the question of whether the amino acid sequence for the vp1 protein of AAVrh74 is, in fact, "at least 95% identical" to the claimed SEQ ID NO: 4 (AAVrh46). The method of calculating this percentage identity could become a point of contention.
  • Technical Questions: A key factual question is whether the accused SRP-9001 product's AAVrh74 capsid protein contains an asparagine (N) at the specific position that "correspond[s] to position 665 in SEQ ID NO: 4." The complaint relies on external patent filings and sequence listings to support this allegation (Compl. ¶33), and the evidence required to prove the structure of the final, manufactured product will be critical.

V. Key Claim Terms for Construction

The Term: "at least 95% identical"

  • Context and Importance: This term is fundamental to the scope of infringement. The dispute may hinge on whether the accused AAVrh74 sequence meets this numerical threshold when compared to the claimed AAVrh46 sequence (SEQ ID NO: 4). Practitioners may focus on this term because the choice of alignment algorithm and its parameters can alter the calculated percentage identity.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The specification refers to determining percent identity using publicly or commercially available computer programs, such as those in the "GCG Wisconsin Package" or "BLAST," which may suggest that a standard, algorithm-based definition was intended (’274 Patent, col. 5:38-50).
    • Evidence for a Narrower Interpretation: The patent distinguishes between "identity" and "homology" or "similarity" (’274 Patent, col. 5:33-35), which could support an argument for a strict, literal interpretation that does not account for conservative amino acid substitutions that might be included under a "similarity" analysis.

The Term: "corresponding to position 665"

  • Context and Importance: The infringement allegation depends on locating this specific amino acid. The alignment of the accused sequence against SEQ ID NO: 4 determines which residue is at the "corresponding" position.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The patent's general reference to standard alignment programs could suggest that the "corresponding" position is simply the one that aligns with position 665 using a conventional algorithm (’274 Patent, col. 5:38-63).
    • Evidence for a Narrower Interpretation: A party could argue that in the context of protein structure and function, "corresponding to" requires more than mere numerical alignment, perhaps implying a conserved structural or functional role, especially if gaps or insertions are present in the alignment near that position.

VI. Other Allegations

Indirect Infringement

  • The complaint alleges Sarepta induces infringement by instructing and contracting with partners, such as Catalent and Thermo Fisher, to manufacture the accused SRP-9001 product (Compl. ¶35). It also alleges contributory infringement, claiming Defendants supply components like plasmids encoding the AAVrh74 capsid protein that have no substantially non-infringing uses (Compl. ¶40).

Willful Infringement

  • Willfulness is alleged based on knowledge of the ’274 Patent acquired "no later than the date of filing of this Complaint" (Compl. ¶41). The complaint alleges that Defendants' continued actions are deliberate and willful in light of this knowledge (Compl. ¶42).

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

  • A core issue will be one of bioinformatic scope: Can the accused AAVrh74 capsid protein be proven to have a sequence that is "at least 95% identical" to the claimed SEQ ID NO: 4 (AAVrh46), and will the court's interpretation of how this identity is calculated and how sequence positions "correspond" place the accused product within the claim's boundaries?
  • A key evidentiary question will be one of factual proof: What evidence can Plaintiffs present to demonstrate the precise amino acid sequence of the AAV capsid used in the SRP-9001 product as manufactured by Defendants, and to confirm the presence of the specific asparagine residue required by Claim 1?