DCT

2:25-cv-05499

Regeneron Pharma Inc v. Amgen Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 2:25-cv-05499, C.D. Cal., 06/17/2025
  • Venue Allegations: Venue is alleged to be proper in the Central District of California because Amgen resides in the district and a substantial part of the events giving rise to the claims occurred there.
  • Core Dispute: Plaintiff alleges that Defendant’s Pavblu® product, a biosimilar of Plaintiff's EYLEA® drug, infringes a patent directed to stable, high-concentration liquid ophthalmic formulations.
  • Technical Context: The technology involves pharmaceutical formulations for biologic drugs used to treat serious eye diseases, such as wet age-related macular degeneration, by inhibiting vascular endothelial growth factor (VEGF).
  • Key Procedural History: This action follows a prior suit between the parties concerning a different set of patents related to the same products, which was consolidated into a multi-district litigation (MDL) in the Northern District of West Virginia. The complaint states that the patent-in-suit issued after the deadline to amend the pleadings in the prior action, necessitating this separate filing. Plaintiff notes its intent to petition the Judicial Panel on Multidistrict Litigation to transfer this case to the West Virginia MDL. The complaint also notes that a court in the MDL previously denied Plaintiff's motion for a preliminary injunction against Defendant.

Case Timeline

Date Event
2006-06-16 '099 Patent Priority Date
2011-01-01 FDA approves Plaintiff's EYLEA® (approximate date from complaint)
2023-01-01 Amgen initiates "Patent Dance" with Regeneron (approximate date from complaint)
2023-10-31 FDA accepts Amgen's application for its biosimilar product
2024-01-10 Regeneron files first patent infringement action against Amgen
2024-04-11 MDL instituted in N.D.W. Va. for EYLEA® biosimilar litigations
2024-05-18 Regulatory exclusivity for EYLEA® expires
2024-08-23 FDA approves Amgen's Pavblu® biosimilar
2024-09-23 MDL Court denies Regeneron's motion for preliminary injunction
2025-06-17 '099 Patent Issues
2025-06-17 Complaint Filed

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

  • Patent Identification: U.S. Patent No. 12,331,099, "VEGF Antagonist Formulations Suitable for Intravitreal Administration," issued June 17, 2025.

U.S. Patent No. 12,331,099 - "VEGF Antagonist Formulations Suitable for Intravitreal Administration"

The Invention Explained

  • Problem Addressed: The patent addresses the inherent instability of protein-based pharmaceuticals, such as VEGF antagonists, in liquid form. These proteins are susceptible to degradation, aggregation, and oxidation, which can compromise their therapeutic efficacy and safety, particularly for formulations intended for direct injection into the eye. (’099 Patent, col. 2:15-20).
  • The Patented Solution: The invention provides specific liquid pharmaceutical formulations designed to maintain the stability of a VEGF "trap" fusion protein. The solution involves combining the protein at a high concentration with a specific recipe of excipients: a buffer, an organic co-solvent (e.g., polysorbate), a tonicity agent (e.g., sodium chloride), and an optional stabilizing agent (e.g., sucrose), all within a defined pH range, to ensure the protein remains in its active, "native" state during storage. (’099 Patent, Abstract; col. 2:44-58).
  • Technical Importance: Developing stable, high-concentration liquid formulations is crucial for biologic drugs, as it enables longer shelf-life, ensures consistent dosing, and reduces the risk of adverse immune reactions caused by protein aggregates. (Compl. ¶¶ 3, 27).

Key Claims at a Glance

  • The complaint asserts independent claims 11 and 26, and dependent claims 12-13, 21, and 27. (Compl. ¶24).
  • Independent Claim 11 requires a liquid ophthalmic formulation with the following essential elements:
    • 40 mg/ml of a specific glycosylated VEGF antagonist fusion protein (amino acids 27-457 of SEQ ID NO: 4)
    • water
    • an organic co-solvent comprising polysorbate
    • a stabilizing agent
    • a pH between 5.8 to 7.0
    • suitability for intravitreal administration
    • a stability requirement wherein at least 98% of the fusion protein remains in its native conformation after two months of storage at 5° C, as measured by size exclusion chromatography
  • Independent Claim 26 is similar to claim 11 but recites different excipients and a different stability requirement. The complaint focuses its detailed allegations on Claim 21, which depends from Claim 11.

III. The Accused Instrumentality

Product Identification

  • Amgen's drug product ABP 938, which is marketed under the name Pavblu®. (Compl. ¶¶ 1, 11).

Functionality and Market Context

  • Pavblu® is a biosimilar of Regeneron's EYLEA® drug. Its active ingredient is aflibercept, a recombinant fusion protein that functions as a VEGF antagonist. (Compl. ¶¶ 9, 27). The complaint alleges that Pavblu® is supplied as an aqueous solution for intravitreal injection at a concentration of 40 mg/mL and contains excipients including polysorbate 80, sucrose, and trehalose, with a pH of 6.2. (Compl. ¶27).
  • The product is a direct market competitor to EYLEA®, having been approved via the Biologics Price Competition and Innovation Act (BPCIA) pathway. (Compl. ¶¶ 9, 15). The complaint cites a report of Amgen earning $99 million in net sales of Pavblu® in the first quarter of 2025. (Compl. ¶19, Ex. 1).

IV. Analysis of Infringement Allegations

The complaint includes a two-column claim chart juxtaposing the limitations of claim 21 with "Exemplary Evidence" drawn from the accused product's label and public information. (Compl. ¶27, pp. 9-10).

  • Claim Chart Summary:
Claim Element (from Independent Claim 11 and Dependent Claim 21) Alleged Infringing Functionality Complaint Citation Patent Citation
A liquid ophthalmic formulation comprising: Pavblu® is supplied as an aqueous solution for intravitreal injection. ¶27 col. 15:11-25
40 mg/ml of a glycosylated vascular endothelial growth factor (VEGF) antagonist fusion protein comprising amino acids 27-457 of SEQ ID NO: 4; The active ingredient in Pavblu® is aflibercept, a glycosylated VEGF antagonist, present at 40 mg/mL. On information and belief, it comprises the specified amino acid sequence. ¶27 col. 3:11-16; col. 16:38-42
water; The Pavblu® label states the formulation contains water for injection. ¶27 col. 6:9-11
an organic co-solvent comprising polysorbate; The Pavblu® label states the formulation contains polysorbate 80. ¶27 col. 2:49-54
and a stabilizing agent, The Pavblu® label states the formulation contains sucrose and trehalose. ¶27 col. 2:54-56
wherein the liquid ophthalmic formulation has a pH of between 6.2 to 6.3, The Pavblu® label states the formulation is an aqueous solution with a pH of 6.2. ¶27 col. 2:65
wherein at least 98% of the VEGF antagonist fusion protein is present in native conformation following storage at 5° C for two months as measured by size exclusion chromatography. On information and belief, the protein in Pavblu® meets this stability requirement. ¶27 col. 15:21-25; col. 19, Tbl. 1
  • Identified Points of Contention:
    • Technical Questions: A primary point of contention will likely be the complaint’s reliance on "information and belief" for critical claim elements. This raises the question: What discovery evidence, such as batch testing data or internal manufacturing specifications, will Plaintiff obtain and present to prove that Amgen's commercially available Pavblu® product meets the quantitative stability limitation requiring "at least 98% of the... protein is present in native conformation" after two months of storage?
    • Scope Questions: The complaint alleges the presence of two stabilizing agents (sucrose and trehalose) to meet the limitation requiring "a stabilizing agent." While standard claim construction practice interprets "a" to mean "one or more," it raises the question of whether Defendant will attempt to argue that its specific combination of stabilizers distinguishes it from the patent's teachings.

V. Key Claim Terms for Construction

  • The Term: "a stabilizing agent"

  • Context and Importance: This term is essential for infringement, as the complaint alleges Pavblu® contains "sucrose and trehalose" to meet this limitation (Compl. ¶27). The construction of this term, particularly whether the singular "a" encompasses a combination of multiple substances, will be important. Practitioners may focus on this term because Defendant could argue that its specific two-sugar combination is not what was contemplated by the patent.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The specification lists multiple examples of stabilizing agents ("sucrose, sorbitol, glycerol, trehalose, or mannitol"), suggesting the term refers to a functional class rather than a specific compound. (’099 Patent, col. 2:55-56).
    • Evidence for a Narrower Interpretation: The specification lists the stabilizing agents with "or," not "and," and the examples appear to use single stabilizing agents. (’099 Patent, col. 2:55-56; col. 3:4-16). A party could argue this suggests the use of only one agent from the class was contemplated.

  • The Term: "native conformation"

  • Context and Importance: This term defines the required stability of the protein, a central technical feature of the invention. Infringement of this limitation is pleaded "on information and belief" and will require technical testing and expert testimony. The precise definition of what constitutes "native conformation" will be critical to assessing infringement.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The claim itself provides the method of measurement: "as measured by size exclusion chromatography." (’099 Patent, col. 15:24-25). A party may argue this explicitly ties the definition to the output of a specific, well-known analytical technique for measuring protein aggregation, giving it a clear and broad functional meaning.
    • Evidence for a Narrower Interpretation: The patent does not provide an explicit definition beyond the measurement method. A party could argue that the term should be limited by the results disclosed in the patent's own stability examples (e.g., Tables 1-8), potentially importing limitations based on the specific performance of the patent's own tested formulations.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges induced infringement under 35 U.S.C. § 271(b) and contributory infringement under § 271(c). The inducement allegation is based on the claim that Amgen provides Pavblu® along with an FDA-approved label and instructions that encourage and direct physicians to use the product in an infringing manner. (Compl. ¶¶ 28, 30, 31).
  • Willful Infringement: Willfulness is alleged based on Amgen’s purported knowledge of the '099 Patent and its family. This knowledge is allegedly derived from its "active monitoring of Regeneron's patents" during the development of its biosimilar and from the prior litigation between the parties, as well as from the filing of the current complaint. (Compl. ¶¶ 29, 33).

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

  • A central issue in this case will be one of technical proof: Can Regeneron produce discovery evidence to convert its "information and belief" pleadings into factual proof, specifically by demonstrating through testing that Amgen's commercial Pavblu® formulation meets the quantitative stability requirement of "at least 98%... native conformation" as defined in claim 11?
  • A key procedural dynamic will shape the litigation: How will the court and parties navigate this follow-on case, which asserts a newly-issued patent against an already-launched product, in relation to the ongoing MDL involving the same parties and products but a different set of patents?
  • The infringement analysis may turn on a question of definitional scope: Will the claim term "a stabilizing agent" be construed broadly to mean "one or more" agents from the specified class, thereby covering Pavblu®'s alleged combination of sucrose and trehalose, or will it be interpreted more narrowly?