DCT

1:24-cv-00882

Genzyme Corp v. Sarepta Therap Inc

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Key Events
Amended Complaint

I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:24-cv-00882, D. Del., 06/04/2025
  • Venue Allegations: Venue is alleged to be proper as Defendants are incorporated in the State of Delaware and therefore reside in the district.
  • Core Dispute: Plaintiff alleges that Defendant’s gene therapy product, Elevidys®, for Duchenne muscular dystrophy, infringes seven patents related to the composition, manufacturing, and analysis of recombinant adeno-associated virus (rAAV) vectors.
  • Technical Context: The technology involves gene therapy using rAAV vectors, a critical and rapidly growing field for treating genetic diseases by delivering therapeutic genes to patients.
  • Key Procedural History: The complaint alleges that Plaintiff Genzyme sent multiple notice letters to Defendant Sarepta regarding infringement, with the first letter and original complaint both dated July 26, 2024. The complaint further notes that on June 15, 2023, Genzyme statutorily disclaimed claims 1 and 2 of U.S. Patent No. 9,051,542, which may impact the scope of the remaining asserted dependent claims of that patent.

Case Timeline

Date Event
2004-06-01 Priority Date for ’542 and ’721 Patents
2010-04-27 Issue Date for U.S. Patent No. 7,704,721
2015-01-20 Priority Date for ’894 and ’326 Patents
2015-06-09 Issue Date for U.S. Patent No. 9,051,542
2016-08-15 Priority Date for ’377, ’880, and ’313 Patents
2022-09-28 Sarepta submits Biologics License Application (BLA) for Elevidys® to FDA
2023-06-15 Genzyme statutorily disclaims claims 1 and 2 of ’542 Patent
2023-06-22 Elevidys® receives FDA accelerated approval
2023-07-11 Issue Date for U.S. Patent No. 11,698,377
2024-06-18 Issue Date for U.S. Patent No. 12,013,326
2024-06-20 Elevidys® receives full FDA approval for an expanded indication
2024-07-09 Issue Date for U.S. Patent No. 12,031,894
2024-07-26 Genzyme files original complaint and sends first notice letter to Sarepta
2024-10-22 Issue Date for U.S. Patent No. 12,123,880
2024-10-31 Genzyme sends second notice letter to Sarepta
2025-05-01 Genzyme sends third notice letter to Sarepta
2025-05-13 Issue Date for U.S. Patent No. 12,298,313
2025-06-04 Genzyme files Second Amended Complaint

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

U.S. Patent No. 9,051,542 - *"Compositions and Methods to Prevent AAV Vector Aggregation"*

  • Patent Identification: U.S. Patent No. 9,051,542, "Compositions and Methods to Prevent AAV Vector Aggregation," issued June 9, 2015 (Compl. ¶25).

The Invention Explained

  • Problem Addressed: During the manufacture of recombinant adeno-associated virus (rAAV) therapeutics, the viral vector particles have a tendency to become insoluble and aggregate into clusters, particularly at the high concentrations required for effective treatment (Compl. ¶¶13-14). This aggregation can lead to reduced production yields, loss of vector functionality, and an increased risk of an immune reaction in patients ('542 Patent, col. 1:44-55; Compl. ¶14).
  • The Patented Solution: The invention is a stable, high-concentration formulation for rAAV vectors. The inventors discovered that using solutions with high ionic strength, created by adding specific multivalent ions (like magnesium or citrate), prevents the rAAV particles from aggregating while maintaining a physiologically acceptable pH and osmolarity ('542 Patent, col. 3:1-15; Compl. ¶15). This allows the rAAV particles to remain soluble and functional during purification and final formulation (Compl. ¶15).
  • Technical Importance: This technology enabled the creation of highly concentrated, stable rAAV drug products suitable for therapeutic use, addressing a key manufacturing and safety hurdle in the development of gene therapies (Compl. ¶14).

Key Claims at a Glance

  • The complaint asserts dependent claims 3 and 6 (Compl. ¶83). These claims incorporate the limitations of independent claim 1, which was statutorily disclaimed on June 15, 2023 (Compl. ¶¶26, 74).
  • The essential elements of the composition, based on the incorporated limitations of claim 1, are:
    • Purified, recombinant AAV vector particles at a concentration between 1×10¹³ vg/ml and 6.4×10¹³ vg/ml;
    • A pH buffer maintaining the composition's pH between 7.5 and 8.0;
    • Excipients including one or more multivalent ions from the group of citrate, sulfate, magnesium, and phosphate;
    • An ionic strength greater than 200 mM; and
    • Storage of the AAV particles without significant aggregation (Compl. ¶74).

U.S. Patent No. 7,704,721 - *"Compositions and Methods to Prevent AAV Vector Aggregation"*

  • Patent Identification: U.S. Patent No. 7,704,721, "Compositions and Methods to Prevent AAV Vector Aggregation," issued April 27, 2010 (Compl. ¶27).

The Invention Explained

  • Problem Addressed: The '721 Patent addresses the same technical problem as its continuation, the ’542 Patent: the aggregation of rAAV particles during the multi-phase manufacturing process, which complicates purification, reduces yields, and poses safety risks ('721 Patent, col. 1:42-53; Compl. ¶13).
  • The Patented Solution: The invention provides a method for preventing aggregation during the manufacturing process. The claimed method involves purifying rAAV virions from a cell lysate using techniques like chromatography and then adding specific salts of multivalent ions to create a purified, high-concentration preparation with an ionic strength sufficient to prevent aggregation ('721 Patent, col. 2:23-32; Compl. ¶101).
  • Technical Importance: This patented method provides a systematic approach to producing the stable, highly concentrated rAAV formulations necessary for effective and safe gene therapy products (Compl. ¶¶14-15).

Key Claims at a Glance

  • The complaint asserts independent claim 1 and dependent claim 7 (Compl. ¶111).
  • The essential steps of independent claim 1 are:
    • Providing a lysate comprising rAAV virions;
    • Purifying the rAAV virions from the lysate using ultracentrifugation and/or chromatography; and
    • Adding salts of multivalent ions (citrate, phosphate, sulfate, or magnesium) to the purified virions to produce a final preparation with:
      • an ionic strength of at least 200 mM,
      • an rAAV concentration exceeding 1×10¹³ vg/ml, and
      • a pH between 7.5 and 8.0 (Compl. ¶101).

Multi-Patent Capsule: U.S. Patent No. 12,031,894

  • Patent Identification: U.S. Patent No. 12,031,894, “Analytical Ultracentrifugation for Characterization of Recombinant Viral Particles,” issued July 9, 2024 (Compl. ¶29).
  • Technology Synopsis: The patent addresses the difficulty in quantitatively distinguishing fully formed, therapeutically active rAAV particles from undesirable empty or partially-filled capsids (Compl. ¶18). It claims methods using analytical ultracentrifugation (AUC) to separate and quantify these different viral species, providing a way to assess the homogeneity and purity of a gene therapy product (Compl. ¶19).
  • Asserted Claims: Claims 1 and 20 are asserted (Compl. ¶139).
  • Accused Features: The complaint alleges that the release testing performed during the manufacture of Elevidys® uses the claimed AUC methods to quantify the percentage of full, empty, and partially filled capsids (Compl. ¶48, 131).

Multi-Patent Capsule: U.S. Patent No. 12,013,326

  • Patent Identification: U.S. Patent No. 12,013,326, “Analytical Ultracentrifugation for Characterization of Recombinant Viral Particles,” issued June 18, 2024 (Compl. ¶31).
  • Technology Synopsis: Related to the ’894 Patent, this invention also uses analytical ultracentrifugation to solve the problem of characterizing heterogeneous rAAV preparations (Compl. ¶19). The claims are directed to methods for determining the size of fragmented genomes within viral particles and the molar concentrations of each species in the mixture (Compl. ¶32).
  • Asserted Claims: Claims 1, 12, and 20 are asserted (Compl. ¶167).
  • Accused Features: The manufacturing and release testing of Elevidys® are accused of using the claimed AUC methods to determine the size of fragmented genomes and quantify different viral particle species (Compl. ¶¶48, 153-154).

Multi-Patent Capsule: U.S. Patent No. 11,698,377

  • Patent Identification: U.S. Patent No. 11,698,377, “Methods for Detecting AAV,” issued July 11, 2023 (Compl. ¶33).
  • Technology Synopsis: The patent addresses the inadequacy of prior art methods, such as antibody-based assays, to accurately and quickly determine the serotype of an AAV particle, which is critical for potency and selectivity (Compl. ¶¶23-24). The invention is a method that involves denaturing the AAV particle and using liquid chromatography/mass spectrometry (LC/MS) to analyze the intact viral proteins (VPs), as the masses of these proteins are indicative of the serotype (’377 Patent, col. 2:4-14; Compl. ¶24).
  • Asserted Claims: Claims 1, 4, 6, and 7 are asserted (Compl. ¶192).
  • Accused Features: The process of manufacturing Elevidys® is accused of infringing, specifically during release testing where the identity of the rAAVrh74 capsid serotype must be confirmed (Compl. ¶¶49, 183).

Multi-Patent Capsule: U.S. Patent No. 12,123,880

  • Patent Identification: U.S. Patent No. 12,123,880, “Methods for Detecting AAV,” issued October 22, 2024 (Compl. ¶35).
  • Technology Synopsis: This patent is directed to solving problems with prior art methods for analyzing viral proteins, which often involved digestion and resulted in inaccurate measurements of post-translational modifications (PTMs) (Compl. ¶21). The claimed invention is a method for analyzing VPs and AAV particles by denaturing them and subjecting the intact proteins to LC/MS, which more accurately determines their masses and can be used to identify PTMs (Compl. ¶22).
  • Asserted Claims: Claims 1, 3, 5, 6, 10, 13, and 14 are asserted (Compl. ¶223).
  • Accused Features: The release testing of Elevidys® is accused of using the claimed LC/MS methods to analyze capsid purity and determine PTMs, with the complaint pointing to Sarepta's own patent application as evidence of its methods (Compl. ¶¶51-53, 216).

Multi-Patent Capsule: U.S. Patent No. 12,298,313

  • Patent Identification: U.S. Patent No. 12,298,313, “Methods for Detecting AAV,” issued May 13, 2025 (Compl. ¶37).
  • Technology Synopsis: Related to the ’377 and ’880 patents, this patent claims a method of preparing a pharmaceutical composition. The method integrates the analytical step of using LC/MS on intact viral proteins to monitor the AAV particles for consistency and identity. If the particles meet specifications (i.e., have less than an undesirable amount of deviation), they are then combined with pharmaceutical excipients (Compl. ¶¶38, 235).
  • Asserted Claims: Claims 20, 26, and 27 are asserted (Compl. ¶250).
  • Accused Features: The full manufacturing process for Elevidys® is accused, wherein AAV particles are allegedly analyzed for consistency using the claimed LC/MS method before being combined with excipients to form the final drug product (Compl. ¶¶237-238, 246).

III. The Accused Instrumentality

Product Identification

  • Elevidys® (delandistrogene moxeparvovec-rokl) (Compl. ¶1).

Functionality and Market Context

  • Elevidys® is a gene therapy for treating Duchenne muscular dystrophy (DMD), a disease caused by a mutation that prevents the body from producing a functional dystrophin protein (Compl. ¶¶39-40). The product uses a recombinant adeno-associated virus vector of the rh74 serotype (rAAVrh74) to deliver a transgene that codes for a shortened, but functional, "micro-dystrophin" protein into a patient's muscle cells (Compl. ¶41). The complaint alleges that Elevidys® has generated substantial revenue, with sales exceeding $820 million in 2024 and $375 million in the first quarter of 2025 alone (Compl. ¶85). The product is manufactured on Sarepta's behalf by contract manufacturers, including Catalent (Compl. ¶¶43, 84).

IV. Analysis of Infringement Allegations

No probative visual evidence provided in complaint.

’542 Patent Infringement Allegations

Claim Element (from Independent Claim 1, incorporated into Asserted Claims 3 and 6) Alleged Infringing Functionality Complaint Citation Patent Citation
A composition for the storage of purified, recombinant adeno-associated virus (AAV) vector particles... Elevidys® is a pharmaceutical composition for the storage of purified rAAV vector particles. ¶75 col. 2:20-22
...purified, recombinant AAV vector particles at a concentration exceeding 1×10¹³ vg/ml up to 6.4×10¹³ vg/ml; Elevidys® has a "nominal concentration of 1.33 x 10¹³ vg/mL." ¶75 col. 10:2-4
...a pH buffer, wherein the pH of the composition is between 7.5 and 8.0; Elevidys® contains a pH buffer and has a pH between 7.5 and 8.0. ¶76 col. 10:5-7
...excipients comprising one or more multivalent ions selected from the group consisting of citrate, sulfate, magnesium, and phosphate; The excipients in Elevidys® include magnesium in the form of magnesium chloride. ¶77 col. 10:8-11
...wherein the ionic strength of the composition is greater than 200 mM, The ionic strength of the Elevidys® composition is alleged to be greater than 200 mM. ¶77 col. 10:11-12
...and wherein the purified AAV vector particles are stored in the composition without significant aggregation. Elevidys® is stored without significant aggregation, as evidenced by FDA requirements for testing "Particulate Matter" and removing vials with visible particles. ¶78 col. 10:14-16
From Dependent Claim 3: ...wherein the Pluronic® F68 is present at a concentration of 0.001% (w/v). Elevidys® contains 0.001% poloxamer 188, which is also known as Pluronic® F68. ¶80 col. 10:21-23
  • Identified Points of Contention:
    • Legal Question: A threshold dispute may arise from Genzyme's statutory disclaimer of independent claim 1. The court will need to determine whether dependent claims 3 and 6 remain enforceable, which typically requires them to be considered as if they incorporate all the limitations of the disclaimed independent claim.
    • Scope Question: The meaning of "without significant aggregation" will be a central point of contention. The complaint relies on inferences from FDA batch release specifications, raising the question of whether meeting regulatory standards for particulate matter is coextensive with the patent's requirement, or if "significant aggregation" has a distinct technical meaning based on the patent's disclosure.

’721 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method of preventing aggregation of...rAAV virions in a purified preparation... The Elevidys® manufacturing process is alleged to be a method that prevents aggregation. ¶103 col. 2:23-26
1) providing a lysate comprising rAAV virions; The manufacture of Elevidys® allegedly involves providing a lysate containing rAAV virions derived from a cell bank. ¶104 col. 10:50-52
2) purifying rAAV virions from the lysate using...chromatography... The rAAV virions for Elevidys® are purified from the lysate using chromatography-based methods. ¶105 col. 10:53-55
3) adding one or more salts of multivalent ions selected from the group consisting of...magnesium to said purified virions to produce a preparation of virions with an ionic strength of at least 200 mM... Magnesium chloride is allegedly added to the purified virions to produce the final Elevidys® preparation with an ionic strength of at least 200 mM. ¶106 col. 10:56-62
...wherein the concentration of purified rAAV virions...exceeds 1×10¹³ vg/ml...and wherein the pH...is between 7.5 and 8.0. The final Elevidys® preparation has a concentration of 1.33 x 10¹³ vg/mL and a pH between 7.5 and 8.0. ¶¶107, 108 col. 10:62-67
  • Identified Points of Contention:
    • Factual Question: A key factual dispute may center on the specifics of the manufacturing process, which are proprietary to Sarepta and its contractors. The infringement allegations rely heavily on "information and belief," and discovery will be required to determine if the actual sequence of purification and formulation steps precisely aligns with the method claimed in the patent.
    • Legal Question: The complaint alleges that Sarepta and its contract manufacturer, Catalent, jointly infringe the method claims (Compl. ¶112). This raises the legal question of whether Genzyme can prove that Sarepta "directs or controls" Catalent's performance of the method steps to the degree required to establish joint infringement under U.S. patent law.

V. Key Claim Terms for Construction

  • The Term: "without significant aggregation" (’542 Patent, Claim 1)

  • Context and Importance: This term is a qualitative limitation central to the infringement analysis for the ’542 patent. Its definition will determine the standard of proof for whether the Elevidys® composition infringes. Practitioners may focus on this term because it is a term of degree, making it a likely subject for dispute over its objective meaning.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The patent abstract states the invention provides "compositions and methods for preparation of concentrated stock solutions of AAV virions without aggregation" ('542 Patent, Abstract). This general statement could support an interpretation where any detectable or functionally meaningful aggregation is "significant."
    • Evidence for a Narrower Interpretation: The patent's examples use dynamic light scattering (DLS) to measure "Average particle radius - Rh (nm)" as an indicator of aggregation ('542 Patent, FIG. 1A). This suggests the possibility that "significant aggregation" could be tied to a quantitative threshold, such as a particle radius exceeding a certain nanometer value as measured by DLS.

  • The Term: "purifying" (’721 Patent, Claim 1)

  • Context and Importance: This term defines a key step in the asserted method claim. The dispute may turn on whether the entire sequence of manufacturing steps constitutes "purifying" as contemplated by the patent, or if the term applies only to specific, discrete actions.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The claim recites "purifying...using...chromatography," which could be read to mean a multi-step process in which chromatography is one of the utilized techniques. The detailed description refers to purification broadly, including steps like "gradient ultracentrifugation" and "column chromatography" as components of a purification process ('721 Patent, col. 10:1-17).
    • Evidence for a Narrower Interpretation: The claim structure separates "purifying" (step 2) from "adding...salts" (step 3). This could support an argument that "purifying" is an action completed before the final formulation step, potentially narrowing the scope of activities that satisfy this limitation.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges both induced and contributory infringement for the asserted patents. Inducement is alleged based on Defendants directing and contracting with third parties (e.g., Catalent) to perform the patented manufacturing methods with knowledge of the patents (Compl. ¶¶86, 114). Contributory infringement is alleged based on Defendants supplying proprietary materials, such as the engineered rAAV virions, for use in the infringing methods, with these materials allegedly having no substantial non-infringing uses (Compl. ¶¶87, 115).
  • Willful Infringement: The complaint alleges willful infringement for all asserted patents. The basis for this allegation is Defendants' alleged knowledge of the patents-in-suit prior to and during the ongoing infringement. This knowledge is purportedly evidenced by, among other things, Genzyme's notice letters, the filing of the original complaint, and Sarepta's prosecution of its own related patent applications, which allegedly involved review of Genzyme's patent family (Compl. ¶¶54-70, 95-97).

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

  • A core issue will be one of joint infringement and evidentiary proof: For the numerous asserted method claims, can Genzyme obtain and present evidence from Sarepta's confidential manufacturing processes to show that the exact steps performed by Sarepta and its contractor, Catalent, meet every claim limitation, and legally establish that Sarepta's oversight constitutes sufficient "direction or control" to create liability for joint infringement?
  • A second key question will be one of claim scope and validity: Given that the patents claim compositions and methods related to foundational techniques in modern gene therapy manufacturing (e.g., using high-salt buffers to reduce aggregation; using AUC and LC/MS to analyze product purity), the case will likely involve significant disputes over whether these claims are broad enough to read on Sarepta’s specific process and, if so, whether they are invalid as obvious over the state of the art at their respective priority dates.
  • A threshold legal question for the ’542 patent will be the effect of statutory disclaimer: Can dependent claims 3 and 6 be asserted when the independent claim from which they depend has been statutorily disclaimed, and how does this affect the infringement and validity analysis for those specific claims?