DCT
1:25-cv-00074
Regeneron Pharma Inc v. Amgen Inc
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Regeneron Pharmaceuticals, Inc. (New York)
- Defendant: Amgen Inc. (Delaware)
- Plaintiff’s Counsel: Umhofer, Mitchell & King LLP
- Case Identification: 2:25-cv-5499, 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 claim occurred there.
- Core Dispute: Plaintiff alleges that Defendant’s biosimilar ophthalmic drug, Pavblu®, infringes a patent covering stable liquid formulations for treating eye diseases.
- Technical Context: The technology concerns pharmaceutical formulations for complex biologic drugs, specifically focusing on maintaining the stability of a protein-based therapeutic for intravitreal injection.
- Key Procedural History: The complaint notes this action follows a complex procedural history between the parties under the Biologics Price Competition and Innovation Act (BPCIA), including a "Patent Dance" and a prior lawsuit ("First Amgen Action") that was consolidated into a multidistrict litigation (MDL). The patent-in-suit was issued after the deadline to amend the complaint in the first action, prompting this separate filing, which Plaintiff intends to petition for transfer to the MDL. The MDL court previously denied Plaintiff's motion for a preliminary injunction against Defendant concerning other patents.
Case Timeline
| Date | Event |
|---|---|
| 2006-06-16 | '099 Patent Priority Date |
| 2011 | FDA approved EYLEA® |
| 2023 | Amgen initiated "Patent Dance" with Regeneron |
| 2023-10-31 | FDA accepted Amgen's aBLA for ABP 938 (Pavblu®) |
| 2024 | Parties completed the "Patent Dance" procedure |
| 2024-01-10 | Regeneron filed the "First Amgen Action" |
| 2024-04-11 | MDL instituted for Aflibercept patent litigation |
| 2024-05-18 | EYLEA® regulatory exclusivity expired |
| 2024-08-23 | FDA approved Amgen's aBLA for Pavblu® |
| 2024-09-23 | MDL Court denied Regeneron's preliminary injunction motion |
| Post 2024-09-23 | Amgen launched Pavblu® |
| 2025-06-17 | U.S. Patent No. 12,331,099 Issued |
| 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.
The Invention Explained:
- Problem Addressed: The patent addresses the inherent instability of protein-based therapeutics in liquid form. Proteins are susceptible to degradation, aggregation, and other degenerative processes, which can compromise their efficacy and safety, particularly for long-term storage (’099 Patent, col. 2:15-20).
- The Patented Solution: The invention provides a stable liquid pharmaceutical formulation for a specific vascular endothelial growth factor (VEGF) antagonist, which is a fusion protein. The solution is a specific recipe combining the fusion protein with a buffer, an organic co-solvent (e.g., polysorbate), a tonicity agent, and an optional stabilizing agent (e.g., sucrose), all maintained 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: Stable, ready-to-use liquid formulations of biologic drugs provide significant advantages over lyophilized (freeze-dried) powders by eliminating the need for reconstitution, thereby increasing convenience, ensuring accurate dosing, and reducing the risk of contamination in a clinical setting (’099 Patent, col. 2:21-24).
Key Claims at a Glance:
- The complaint asserts independent claim 11 and dependent claims 12-13, 21, 26, and 27 (Compl. ¶26).
- Independent Claim 11 is directed to 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 and 7.0;
- suitability for intravitreal administration; and
- a stability requirement wherein at least 98% of the fusion protein remains in native conformation after two months of storage at 5° C.
- The complaint reserves the right to assert additional claims (’099 Patent, Claim 11).
III. The Accused Instrumentality
Product Identification: Amgen’s ABP 938, a drug product marketed under the name Pavblu® (Compl. ¶11).
Functionality and Market Context:
- Pavblu® is a biosimilar version of Regeneron's EYLEA® product, containing the active ingredient aflibercept, which is a VEGF antagonist fusion protein (Compl. ¶1; ¶27).
- It is provided as a sterile, aqueous solution in vials and pre-filled syringes for intravitreal injection to treat serious eye diseases, including neovascular (wet) age-related macular degeneration (Compl. ¶11; ¶27).
- The complaint alleges significant commercial activity, citing an exhibit that Amgen reported $99 million in net sales of Pavblu® in the first quarter of 2025 (Compl. ¶19).
IV. Analysis of Infringement Allegations
The complaint presents its infringement theory for Claim 21 in a detailed, two-column chart mapping claim elements to evidence from the accused product's label (Compl. ¶27, pp. 9-10). The core allegations for the asserted independent claim and the specifically charted dependent claim are summarized below.
'099 Patent Infringement Allegations
| 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 for ophthalmic conditions. | ¶27 | col. 2:44-48 |
| 40 mg/ml of a glycosylated vascular endothelial growth factor (VEGF) antagonist fusion protein comprising amino acids 27-457 of SEQ ID NO: 4; | Pavblu®'s active ingredient is aflibercept, a glycosylated VEGF antagonist, present at 40 mg/mL and, on information and belief, comprising amino acids 27-457 of SEQ ID NO: 4. | ¶27 | col. 3:10-16; col. 2:38-42 |
| water; | The Pavblu® label states the formulation contains water for injection. | ¶27 | col. 5:58-63 |
| an organic co-solvent comprising polysorbate; | The Pavblu® label states the formulation contains polysorbate 80. | ¶27 | col. 2:50-53 |
| 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... | On information and belief, the protein in Pavblu® meets this stability requirement. | ¶27 | col. 8:51-65 |
- Identified Points of Contention:
- Technical Questions: A primary factual dispute may center on the stability limitation ("at least 98%... in native conformation"). The complaint alleges this "On information and belief" (Compl. ¶27). This raises the evidentiary question of whether Regeneron can prove through testing that Amgen's product, as sold, actually meets this specific quantitative stability threshold required by the claim.
- Scope Questions: The interpretation of "a stabilizing agent" could be contested. While the complaint identifies sucrose and trehalose in Pavblu® as meeting this limitation (Compl. ¶27), the defense may raise the question of whether both components function as stabilizing agents in the context of the specific accused formulation, potentially seeking a narrower functional definition.
V. Key Claim Terms for Construction
The Term: "stabilizing agent"
- Context and Importance: This term is an essential component of the claimed formulation. Its construction is critical because the presence and identity of the stabilizer distinguish the claimed invention from the prior art and define the scope of infringement. Practitioners may focus on this term because Amgen could argue that the excipients in its formulation (sucrose and trehalose) do not function in the manner contemplated by the patent, or that the term requires a specific functional result.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification provides a list of examples, stating the stabilizing agent "may be sucrose, sorbitol, glycerol, trehalose, or mannitol," which may support an interpretation that the term covers a known class of sugar-based excipients (’099 Patent, col. 2:54-56).
- Evidence for a Narrower Interpretation: The patent does not provide an explicit definition. A party could argue the term should be functionally defined by its effect on the formulation's stability, as recited elsewhere in the claim. The examples show formulations containing a stabilizer (sucrose) that achieve high stability, which could be used to argue the term is tied to achieving that specific result (’099 Patent, col. 8:46-51, Table 1).
The Term: "native conformation"
- Context and Importance: This term is part of the key quantitative limitation that defines the required stability of the formulation ("at least 98%... in native conformation"). Its definition will directly impact how infringement is measured and whether the accused product meets this critical claim element.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The patent does not explicitly define "native conformation," which may support adopting its plain and ordinary meaning: the correctly folded, biologically active three-dimensional structure of the protein.
- Evidence for a Narrower Interpretation: Claim 11 itself specifies that the measurement is performed by "size exclusion chromatography." A party may argue that this contextually limits the definition of "native conformation" to only what is measured as non-aggregated by that specific analytical technique, as demonstrated in the patent's examples (’099 Patent, col. 8, Table 1).
VI. Other Allegations
- Indirect Infringement: The complaint alleges that Amgen induces infringement by providing Pavblu® with its FDA-approved label, which contains instructions for physicians to use the product in a manner that directly infringes the ’099 Patent (Compl. ¶30, ¶31).
- Willful Infringement: The complaint alleges willful infringement based on both pre-suit and post-suit knowledge. It asserts post-suit knowledge from the filing of the complaint and pre-suit knowledge based on Amgen’s alleged "active monitoring of Regeneron's patents and patent applications" in the same family as those already in litigation between the parties (Compl. ¶29, ¶33).
VII. Analyst’s Conclusion: Key Questions for the Case
- A key evidentiary question will be one of demonstrable stability: Can Regeneron produce testing data to prove its "information and belief" allegation that Amgen's Pavblu® product meets the quantitative claim limitation of having at least 98% of its protein in native conformation after two months of storage, or will there be a fundamental mismatch in the technical evidence?
- The infringement analysis will likely turn on a question of definitional scope: Will the term "stabilizing agent" be construed broadly to cover common pharmaceutical excipients like those in Pavblu®, or will the court adopt a narrower, functional definition that Amgen may argue its product does not satisfy?
- A central issue for damages will be culpability: Will Regeneron succeed in proving that Amgen was "willfully blind" to its infringement based on pre-suit monitoring of Regeneron's patent family, or will any potential finding of willfulness be limited to Amgen's conduct after receiving notice of the ’099 Patent via this lawsuit?