DCT

1:24-cv-00882

Genzyme Corp v. Sarepta Therap Inc

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Key Events
Complaint

I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:24-cv-00882, D. Del., 07/26/2024
  • Venue Allegations: Venue is alleged to be proper in the District of Delaware as both Defendant entities are incorporated in Delaware and therefore reside in the district.
  • Core Dispute: Plaintiff alleges that Defendant’s gene therapy product for Duchenne muscular dystrophy, Elevidys®, infringes patents related to compositions and methods for stabilizing high-concentration recombinant adeno-associated virus (rAAV) vectors against aggregation.
  • Technical Context: The technology addresses the challenge of preventing therapeutic virus particles in gene therapies from clumping together, which is critical for ensuring product stability, manufacturing yield, and clinical efficacy.
  • Key Procedural History: Plaintiff statutorily disclaimed claims 1 and 2 of U.S. Patent No. 9,051,542 on June 15, 2023; the current suit asserts dependent claims that incorporate the limitations of the disclaimed independent claim. Both patents-in-suit are set to expire on June 1, 2025.

Case Timeline

Date Event
2004-06-01 Priority Date for ’542 and ’721 Patents
2010-04-27 ’721 Patent Issue Date
2015-06-09 ’542 Patent Issue Date
2023-06-15 Plaintiff disclaims claims 1 and 2 of the ’542 Patent
2023-06-22 Initial FDA approval for Defendant's Elevidys® product
2024-06-20 Expanded FDA approval for Defendant's Elevidys® product
2024-07-26 Complaint Filing Date
2025-06-01 Expiration Date for ’542 and ’721 Patents

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

U.S. Patent No. 9,051,542 - “Compositions and Methods to Prevent AAV Vector Aggregation” (issued June 9, 2015)

The Invention Explained

  • Problem Addressed: The patent addresses the technical challenge that recombinant adeno-associated virus (rAAV) particles, used in gene therapy, tend to aggregate or clump together when prepared in highly concentrated solutions (Compl. ¶¶13-14). This aggregation can reduce manufacturing yields, compromise the vector's functionality, and potentially trigger adverse immune reactions in patients (Compl. ¶¶13-14).
  • The Patented Solution: The invention is a pharmaceutical composition designed to store purified rAAV vectors at high concentrations without causing them to aggregate. This is achieved by formulating the vectors in a solution with a high ionic strength (greater than 200 mM) created by specific multivalent ions (e.g., citrate, sulfate, magnesium, phosphate), while maintaining a pH between 7.5 and 8.0 ('542 Patent, Abstract; col. 6:45-59).
  • Technical Importance: This formulation technology enables the production of stable, highly concentrated gene therapy products, which is essential for effective clinical dosing, particularly in applications requiring small-volume administration (Compl. ¶14).

Key Claims at a Glance

  • The complaint asserts dependent claims 3 and 6 (Compl. ¶37). These claims incorporate the limitations of independent claim 1, which has been statutorily disclaimed by the Plaintiff (Compl. ¶¶17, 28).
  • Independent Claim 1 (incorporated): The essential elements are:
    • A composition for the storage of purified, recombinant adeno-associated virus (AAV) vector particles
    • Comprising purified, recombinant AAV vector particles at a concentration exceeding 1x10¹³ vg/ml up to 6.4x10¹³ vg/ml
    • A pH buffer, wherein the pH of the composition is between 7.5 and 8.0
    • Excipients comprising one or more multivalent ions (citrate, sulfate, magnesium, or phosphate)
    • Wherein the ionic strength of the composition is greater than 200 mM
    • And wherein the purified AAV vector particles are stored in the composition without significant aggregation
  • The complaint reserves the right to assert additional claims (Compl. ¶37).

U.S. Patent No. 7,704,721 - “Compositions and Methods to Prevent AAV Vector Aggregation” (issued April 27, 2010)

The Invention Explained

  • Problem Addressed: Similar to its continuation ('542 Patent), this patent confronts the problem of rAAV vector aggregation during the manufacturing process, which limits vector solubility and creates inconsistencies in purified vector preparations ('721 Patent, col. 1:40-44, col. 2:7-12).
  • The Patented Solution: The patent claims a method for preventing rAAV aggregation. The core of the method involves purifying virions from a cell lysate (e.g., via chromatography) and then adding salts of multivalent ions to create a final preparation with high ionic strength (at least 200 mM), high vector concentration, and a specific pH range (7.5-8.0), thereby keeping the virions soluble and non-aggregated ('721 Patent, col. 12:9-24).
  • Technical Importance: The invention provides a defined process for reliably manufacturing stable, high-concentration rAAV vectors, addressing a key challenge in the scalable production of gene therapies ('721 Patent, col. 2:50-59).

Key Claims at a Glance

  • The complaint asserts independent claim 1 and dependent claim 7 (Compl. ¶56).
  • Independent Claim 1: The essential elements are:
    • A method of preventing aggregation of rAAV virions in a purified preparation
    • Providing a lysate comprising rAAV virions
    • Purifying rAAV virions from the lysate using ultracentrifugation and/or chromatography
    • Adding one or more salts of multivalent ions (citrate, phosphate, sulfate, magnesium) to the purified virions
    • To produce a preparation with an ionic strength of at least 200 mM, a virion concentration exceeding 1x10¹³ vg/ml, and a pH between 7.5 and 8.0
  • The complaint reserves the right to assert additional claims (Compl. ¶56).

III. The Accused Instrumentality

Product Identification

  • The accused instrumentality is Elevidys® (delandistrogene moxeparvovec-rokl), including the product composition and the methods used for its manufacture, use, sale, and offer for sale (Compl. ¶¶1, 27, 45).

Functionality and Market Context

  • Elevidys® is described as a one-time rAAV gene therapy for treating Duchenne muscular dystrophy (DMD) (Compl. ¶20). It uses a non-replicating rAAV vector of serotype rh74 to deliver a transgene encoding a functional, albeit shortened, "micro-dystrophin" protein to a patient's muscle cells (Compl. ¶22). The complaint alleges that Elevidys® is a significant commercial product, citing revenues of more than $200 million from U.S. sales in 2023 alone (Compl. ¶39).

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 AAV vector particles Elevidys® is alleged to be a pharmaceutical composition for the storage of purified, rAAV vector particles (Compl. ¶29). ¶29 col. 13:15-24
purified, recombinant AAV vector particles at a concentration exceeding 1x10¹³ vg/ml up to 6.4x10¹³ vg/ml Elevidys® is alleged to have a "nominal concentration of 1.33 x 10¹³ vg/mL," which falls within the claimed range (Compl. ¶29). ¶29 col. 13:18-19
a pH buffer, wherein the pH of the composition is between 7.5 and 8.0 Elevidys® allegedly contains a tromethamine HCl and tromethamine buffer, and its pH can be calculated to be between 7.5 and 8.0 based on its components (Compl. ¶30). ¶30 col. 13:20-21
excipients comprising one or more multivalent ions selected from the group consisting of citrate, sulfate, magnesium, and phosphate The Elevidys® formulation allegedly includes magnesium in the form of magnesium chloride (Compl. ¶31). ¶31 col. 13:22-23
wherein the ionic strength of the composition is greater than 200 mM The ionic strength of the Elevidys® composition, containing 200 mM sodium chloride and 1 mM magnesium chloride, is alleged to be greater than 200 mM (Compl. ¶¶30-31). ¶31 col. 13:23-24
wherein the purified AAV vector particles are stored in the composition without significant aggregation Elevidys® is allegedly stored without significant aggregation, based on FDA requirements to test for "Particulate Matter" and reject batches with visible particles (Compl. ¶32). ¶32 col. 13:24-27
From Dependent Claim 3: wherein the Pluronic® F68 is present at a concentration of 0.001% (w/v) Elevidys® is alleged to contain 0.001% poloxamer 188, which is identified as Pluronic® F68 (Compl. ¶¶33-34). ¶34 col. 14:28-30
From Dependent Claim 6: wherein recovery of the purified, recombinant virus particles is at least about 90% following filtration...through a 0.22 µm filter The complaint alleges on information and belief that the manufacturing of Elevidys® involves sterile filtration through a 0.22 µm filter and that the resulting yield is at least 90% (Compl. ¶36). ¶36 col. 14:38-42
  • Identified Points of Contention:
    • Scope Questions: A central question may be the definition of "without significant aggregation." The complaint points to FDA release specifications and the removal of vials with visible particles as evidence of this feature (Compl. ¶32). A court may need to determine if this industry practice aligns with the patent's description, which characterizes aggregation using dynamic light scattering measurements of particle radius ('542 Patent, col. 9:25-41).
    • Technical Questions: The allegation that Elevidys® achieves "at least about 90%" recovery after filtration is made on "information and belief" based on an inference about FDA-approved specifications (Compl. ¶36). This assertion will likely require factual evidence obtained through discovery for substantiation.

’721 Patent Infringement Allegations

Claim Element (from Independent Claim 1, incorporated into asserted Claim 7) Alleged Infringing Functionality Complaint Citation Patent Citation
A method of preventing aggregation...in a purified preparation of rAAV virions The manufacturing of Elevidys® is alleged to be a method designed to prevent aggregation, as evidenced by product release specifications requiring testing for and removal of particulate matter (Compl. ¶48). ¶48 col. 12:9-11
1) providing a lysate comprising rAAV virions The Elevidys® manufacturing process allegedly begins with a cell bank, which is used to generate the rAAV virions, thereby providing a lysate (Compl. ¶49). ¶49 col. 12:12
2) purifying rAAV virions from the lysate using...chromatography Elevidys® is allegedly manufactured using a "chromatography-based purification method" to purify the rAAV virions from the lysate and separate full capsids from empty ones (Compl. ¶¶47, 50). ¶¶47, 50 col. 12:13-15
3) adding one or more salts of multivalent ions...to said purified virions The process allegedly involves adding magnesium chloride, a salt of a multivalent ion, to the purified virions to create the final Elevidys® composition (Compl. ¶51). ¶51 col. 12:16-18
to produce a preparation...with an ionic strength of at least 200 mM The addition of salts, including 200 mM sodium chloride and 1 mM magnesium chloride, allegedly results in a final preparation with an ionic strength of at least 200 mM (Compl. ¶51). ¶51 col. 12:19-20
wherein the concentration of purified rAAV virions...exceeds 1x10¹³ vg/ml Elevidys® is alleged to be prepared to a "nominal concentration of 1.33 x 10¹³ vg/mL," which meets the claimed concentration threshold (Compl. ¶52). ¶52 col. 12:21-22
wherein the pH of the purified preparation...is between 7.5 and 8.0 The pH of the final Elevidys® preparation is alleged to be between 7.5 and 8.0, based on its buffered components (Compl. ¶53). ¶53 col. 12:23-24
From Dependent Claim 7: recovery of the virions is at least about 90% following filtration...through a 0.22 µm filter On information and belief, the manufacturing process for Elevidys® allegedly includes a sterile filtration step using a 0.22 µm filter after the addition of magnesium chloride, with a recovery yield of at least 90% (Compl. ¶55). ¶55 col. 12:37-41
  • Identified Points of Contention:
    • Scope Questions: The dispute over the meaning of "preventing aggregation" is also relevant here. Additionally, the complaint alleges joint infringement, asserting that the defendant directs and controls its manufacturing partner, Catalent, to perform the claimed method steps (Compl. ¶57). The nature and extent of this direction and control will be a central legal question.
    • Technical Questions: As with the '542 Patent, the allegation regarding the "at least about 90%" filtration recovery is based on "information and belief" and will require factual substantiation (Compl. ¶55).

V. Key Claim Terms for Construction

  • The Term: "without significant aggregation" ('542 Patent, claim 1) / "preventing aggregation" ('721 Patent, claim 1)

    • Context and Importance: This concept is the central purpose of the inventions. Its definition will be critical for determining whether the accused product infringes, as the complaint relies on FDA manufacturing standards as evidence of non-aggregation. Practitioners may focus on this term because its construction could determine whether infringement can be shown by adherence to regulatory norms or requires specific scientific measurements as detailed in the patent.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The claims do not provide a specific numerical threshold for "significant," which may support an interpretation based on the ordinary meaning of the term in the context of pharmaceutical manufacturing, potentially encompassing standards like the absence of visible particles cited in the complaint (Compl. ¶32).
      • Evidence for a Narrower Interpretation: The specification repeatedly uses dynamic light scattering (DLS) to measure aggregation, stating that an average particle radius (Rh) value ">20 nm" is used "to indicate the occurrence of some level of aggregation" ('542 Patent, col. 9:28-33). A defendant could argue this provides a more specific, limiting definition.

  • The Term: "purified" ('542 Patent, claim 1; '721 Patent, claim 1)

    • Context and Importance: The claims apply to compositions and methods involving "purified" rAAV particles. The degree of purity required by this term could be a point of contention.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The term could be construed broadly to mean that the virions have been separated from the majority of host cell components. The '721 Patent specification describes purification using techniques like "ultracentrifugation and/or chromatography," suggesting these are exemplary methods rather than an exhaustive list (col. 12:13-15).
      • Evidence for a Narrower Interpretation: The specification distinguishes between different purification methods and their outcomes, noting that vectors purified by column chromatography (Method 2) "contain empty capsids, ranging from 3-10 empty capsids per vector genome" ('542 Patent, col. 11:47-50). A party could argue that "purified" implies a specific quality standard, such as a particular ratio of full-to-empty capsids or the removal of a certain amount of non-vector DNA.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges both induced and contributory infringement for both patents.
    • Inducement is alleged based on Defendants providing Elevidys® to third parties with a label and instructions for use, and by contracting with and instructing Catalent to perform the patented methods, all with alleged knowledge of the patents (Compl. ¶¶40, 59).
    • Contributory infringement is alleged based on Defendants supplying "engineered rAAV particles for formulation into finished drug product," which are asserted to be material components with no substantially non-infringing uses (Compl. ¶¶41, 60).
  • Willful Infringement: The complaint alleges that infringement is "deliberate and willful at least as of the date of the filing of the complaint" (Compl., Prayer for Relief ¶B). The pleading does not contain specific factual allegations of pre-suit knowledge, suggesting the willfulness claim may be primarily directed at post-filing conduct.

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

  • A core issue will be one of claim construction: can the term "without significant aggregation," which the patent specification links to specific biophysical measurements (DLS), be construed to be met by adherence to broader regulatory standards for particulate matter, as the complaint alleges?
  • A key evidentiary question will be one of factual proof: can the Plaintiff substantiate its "information and belief" allegations, particularly the claim that the accused manufacturing process achieves a filtration recovery yield of "at least about 90%," a specific numerical limitation in both asserted patents?
  • A central legal question will be one of divided infringement: does the alleged relationship between Sarepta and its manufacturing contractor, Catalent, satisfy the "direction or control" standard required to establish liability for joint infringement of the asserted method claims?