DCT
7:20-cv-08255
Allele Biotechnology Pharma Inc v. Regeneron Pharma Inc
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Allele Biotechnology and Pharmaceuticals, Inc. (California)
- Defendant: Regeneron Pharmaceuticals, Inc. (New York)
- Plaintiff’s Counsel: Perkins Coie LLP
- Case Identification: 7:20-cv-08255, S.D.N.Y., 01/18/2022
- Venue Allegations: Venue is alleged to be proper as Defendant is incorporated in New York and maintains its principal place of business and a registered office within the Southern District of New York. The complaint also notes that Defendant has previously availed itself of this forum for patent litigation.
- Core Dispute: Plaintiff alleges that Defendant’s use of a patented fluorescent protein (mNeonGreen) as a research tool in the development and testing of its anti-COVID-19 antibody cocktail infringes a patent covering the protein itself.
- Technical Context: Fluorescent proteins are fundamental tools in molecular biology, acting as glowing tags that allow researchers to visualize, track, and quantify biological processes within living cells.
- Key Procedural History: The complaint anticipates a central legal dispute over the 35 U.S.C. § 271(e)(1) "safe harbor," arguing that Defendant's use of the patented protein as a research tool is a commercial use not reasonably related to developing information for FDA submission. Plaintiff also alleges pre-suit knowledge of the patent based on multiple ignored attempts to initiate licensing discussions with Defendant.
Case Timeline
| Date | Event |
|---|---|
| 2012-07-24 | ’221 Patent Priority Date |
| 2019-03-05 | ’221 Patent Issue Date |
| 2020-06-01 | Regeneron's Hansen et al. paper first published, allegedly detailing use of mNeonGreen |
| 2020-06-01 | Regeneron's Baum et al. paper first published, allegedly detailing use of mNeonGreen |
| 2020-06-26 | Plaintiff allegedly contacts Defendant regarding licensing |
| 2020-07-02 | Plaintiff allegedly contacts Defendant regarding licensing |
| 2020-07-09 | Plaintiff allegedly contacts Defendant regarding licensing |
| 2020-07-01 | Regeneron's Yurkovetskiy et al. paper published, allegedly detailing use of mNeonGreen |
| 2022-01-18 | Second Amended Complaint Filing Date |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 10,221,221 - Monomeric Yellow-Green Fluorescent Protein from Cephalochordate
Issued: March 5, 2019
The Invention Explained
- Problem Addressed: The patent’s background section notes that while fluorescent proteins (FPs) derived from jellyfish have become essential tools for biological imaging, there remains a need for improved FPs in the green and yellow portions of the spectrum (’221 Patent, col. 1:49-57). A key limitation of many naturally occurring FPs is that they exist as oligomers (e.g., tetramers), which can interfere with the function of proteins they are attached to (fusion tags), limiting their utility in research (Compl. ¶ 17).
- The Patented Solution: The invention is a novel monomeric yellow-green fluorescent protein, named "mNeonGreen," engineered from a naturally tetrameric FP found in the marine invertebrate Branchiostoma lanceolatum (’221 Patent, col. 1:21-26). The inventors used computational structure prediction and modeling to identify and modify the specific amino acids at the protein interfaces responsible for forming a tetramer, thereby creating a stable and highly bright monomeric version (’221 Patent, col. 2:10-15; col. 5:2-8).
- Technical Importance: The resulting mNeonGreen protein is described as one of the brightest and most stable monomeric FPs in its class, making it an exceptionally useful biomarker and fusion tag for advanced imaging applications, including super-resolution microscopy and Förster resonance energy transfer (FRET) experiments (Compl. ¶¶ 18-20; ’221 Patent, col. 1:28-35).
Key Claims at a Glance
- The complaint asserts infringement of "one or more claims" without specifying them (Compl. ¶ 51). Independent claim 1 is representative:
- A non-naturally occurring isolated monomeric or dimeric lanYFP fluorescent protein
- comprising a polypeptide having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 1
- wherein the protein comprises at least one mutation selected from a specified group of 21 possible mutations.
- The complaint does not explicitly reserve the right to assert dependent claims.
III. The Accused Instrumentality
Product Identification
The accused instrumentality is not a product sold by Regeneron, but rather its alleged use of the mNeonGreen protein technology covered by the ’221 patent (Compl. ¶¶ 28, 51-52).
Functionality and Market Context
The complaint alleges that Regeneron used mNeonGreen as a research tool in the development and production of its commercial anti-COVID-19 antibody products (Compl. ¶ 34). Specifically, Regeneron allegedly incorporated the gene for mNeonGreen into a viral reporter construct (pVSV-SARS-CoV-2-S(mNeon)) (Compl. ¶ 29). This construct was used in neutralization assays where mNeonGreen expression served as a measurable "read-out for virus infectivity," allowing Regeneron to screen and test the efficacy of its therapeutic antibodies (Compl. ¶¶ 29, 34). The complaint alleges this use is commercial in nature and was undertaken for validation, quality control, and promotion of Regeneron's own products (Compl. ¶ 35).
IV. Analysis of Infringement Allegations
No probative visual evidence provided in complaint.
’221 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A non-naturally occurring isolated monomeric or dimeric lanYFP fluorescent protein... | Defendant is alleged to have used "mNeonGreen," a protein described in the complaint as a novel monomeric fluorescent protein derived from a tetrameric yellow FP. | ¶¶ 18, 19, 29 | col. 1:21-26 |
| ...comprising a polypeptide having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 1... | The protein allegedly used by Defendant is identified as "mNeonGreen," which Plaintiff markets and which corresponds to the patented protein of SEQ ID NO: 1. The complaint cites scientific papers by Defendant's employees that explicitly refer to using "mNeonGreen." | ¶¶ 23, 29, 31 | col. 7:20-27 |
| ...wherein the protein comprises at least one mutation selected from the group consisting of: F15I, R25Q, A45D, Q56H, F67Y, K79V, S100V, F115A, I118K, V140R, T141S, M143K, L144T, D156K, T158S, S163N, Q168R, V171A, N174T, I185Y, and F192Y. | Because the protein allegedly used is identified by name as "mNeonGreen," the complaint alleges it necessarily contains the specific, recited mutations that define the patented invention and distinguish it from the naturally occurring protein. | ¶¶ 19, 23, 29 | col. 6:40-44 |
Identified Points of Contention
- Legal Question (Safe Harbor): The central dispute foreshadowed by the complaint is legal rather than technical. The key question will be whether Defendant's use of mNeonGreen as a research tool for developing its own therapeutic product is shielded from infringement liability by the 35 U.S.C. § 271(e)(1) safe harbor. The complaint argues the safe harbor does not apply because mNeonGreen is a research tool, not a drug, and was not used to develop a generic or biosimilar version of a patented product (Compl. ¶¶ 39-41, 55).
- Factual Question (Identity): While the complaint's evidence appears strong on this point, a factual question for discovery will be to obtain the exact amino acid sequence of the fluorescent protein construct actually used by Defendant and confirm that it meets the "at least 95% sequence identity" and specific mutation limitations of the asserted claims.
V. Key Claim Terms for Construction
- The Term: "monomeric"
- Context and Importance: The patent’s primary innovation is the conversion of a tetrameric protein into a monomeric one to improve its function as a research tool. The definition of "monomeric" is therefore foundational to the claim scope. Practitioners may focus on this term because the method of determining the oligomeric state (e.g., size exclusion chromatography) could become a point of evidentiary dispute.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: Claim 1 recites "monomeric or dimeric," suggesting the claim is not strictly limited to monomers and could cover proteins that do not fully achieve a monomeric state but are no longer tetrameric.
- Evidence for a Narrower Interpretation: The patent specification repeatedly identifies the invention, mNeonGreen, as the "monomeric" variant and provides an exemplary experimental result (FIG. 1) showing its successful separation from dimeric and tetrameric forms via size exclusion chromatography, which could be argued to define the standard for what "monomeric" means in the context of the patent (’221 Patent, FIG. 1; col. 2:2-3).
VI. Other Allegations
- Indirect Infringement: The complaint alleges that Defendant induced infringement by publishing scientific papers and press releases that "instruct others on how to use the patented technology" (Compl. ¶ 48). These publications allegedly enable and encourage the broader scientific community to replicate the infringing use of mNeonGreen.
- Willful Infringement: The complaint alleges willful infringement based on pre-suit knowledge. It states that Plaintiff contacted Defendant’s business development group on three separate occasions in June and July 2020 to discuss licensing the ’221 patent, but its "overtures were ignored" (Compl. ¶¶ 43-46). This alleged conduct is presented as evidence that Defendant had actual knowledge of the patent and its infringement but continued its activities regardless (Compl. ¶¶ 53, 56, 58).
VII. Analyst’s Conclusion: Key Questions for the Case
- A core issue will be one of statutory interpretation: Does the § 271(e)(1) safe harbor, designed to facilitate the development of generic drugs, extend to protect the unlicensed use of a patented research tool when that tool is used to develop a separate, non-competing therapeutic product? The court's resolution of this question may be dispositive.
- A second key question will be one of willfulness and damages: Should the case proceed past the safe harbor issue, the court will examine the factual record surrounding Plaintiff's alleged attempts to license the technology. The determination of whether Defendant's decision to use the technology without a license, after being contacted, was objectively reckless will be central to any finding of willfulness and potential enhancement of damages.