DCT
1:14-cv-01650
Regeneron Pharma Inc v. Merus BV
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Regeneron Pharmaceuticals, Inc. (New York)
- Defendant: Merus B.V. (The Netherlands)
- Plaintiff’s Counsel: Irell & Manella LLP
- Case Identification: 1:14-cv-01650, S.D.N.Y., 03/11/2014
- Venue Allegations: Plaintiff Regeneron alleges venue is proper because Defendant Merus is subject to personal jurisdiction in the district through its business dealings and has committed acts of infringement in the state. Regeneron’s principal place of business is also located within the district.
- Core Dispute: Plaintiff alleges that Defendant’s genetically modified "MeMo" mouse infringes a patent related to genetically engineered mice that produce hybrid human-mouse antibodies.
- Technical Context: The technology concerns the genetic engineering of non-human animals to create a functional immune system that produces human or partially human antibodies for use as biopharmaceutical therapeutics.
- Key Procedural History: The complaint alleges Defendant Merus was aware of the patent-in-suit’s parent patent family, having cited a parent patent as prior art in its own prosecution and having participated in European opposition proceedings for a related European patent, which may be relevant to the allegation of willful infringement.
Case Timeline
| Date | Event |
|---|---|
| 2000-10-31 | '018 Patent Earliest Priority Date (U.S. Prov. 60/244,665) |
| 2013-08-06 | U.S. Patent No. 8,502,018 Issues |
| 2014-03-11 | Complaint Filed |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 8,502,018 - "Methods of modifying eukaryotic cells"
The Invention Explained
- Problem Addressed: The patent describes the difficulty of creating antibodies in non-human animals for use as human therapeutics, as such antibodies are often rejected by the human immune system. (Compl. ¶15). Prior methods for creating "humanized" antibodies or fully human antibodies in transgenic mice suffered from technical limitations, including poor immune response and health issues in the animals, because the engineered human antibody genes did not interact properly with the native mouse immune system components. (Compl. ¶15, ¶23; ’018 Patent, col. 29:5-14).
- The Patented Solution: The invention is a genetically modified mouse wherein the endogenous mouse immunoglobulin variable region genes are replaced, in situ, with their human counterparts, while retaining the mouse constant region genes. ('018 Patent, col. 29:38-44). The resulting "hybrid" antibodies—with a human variable region and a mouse constant region—are intended to provoke a more robust and diverse immune response, as the mouse constant region can properly interact with the mouse's B-cell signaling components, leading to better antibody maturation and affinity. ('018 Patent, col. 29:55-65).
- Technical Importance: This approach allows for the in vivo generation of a diverse repertoire of high-affinity human-like antibodies that can be more efficiently developed into human therapeutics compared to previous methods. (Compl. ¶23).
Key Claims at a Glance
- The complaint asserts infringement of one or more claims, including dependent claim 9, which relies on independent claim 1. (Compl. ¶22, ¶25).
- The essential elements of claims 1 and 9 combined are:
- A genetically modified mouse,
- comprising in its germline human unrearranged variable region gene segments inserted at an endogenous mouse immunoglobulin locus,
- wherein the mouse produces an antibody that comprises a human variable region and a mouse constant region. (’018 Patent, col. 34:25-28, 48-50).
- The complaint alleges infringement of "one or more claims of the '018 Patent, including for example claim 9." (Compl. ¶25).
III. The Accused Instrumentality
Product Identification
The accused instrumentalities are "Merus's MeMo mouse and related products and technologies." (Compl. ¶25).
Functionality and Market Context
- The complaint alleges that the MeMo mouse is a genetically modified animal whose "sole business purpose appears to be directed to a genetically modified mouse that infringes Regeneron's intellectual property." (Compl. ¶4).
- The infringement allegations assert that the MeMo mouse possesses the features of the asserted claims, namely that it "comprises, in its germline, at least human unrearranged heavy chain variable region gene segments inserted at an endogenous mouse immunoglobulin locus and that produces an antibody comprising a human variable region and a mouse constant region." (Compl. ¶24). The complaint does not provide further independent technical detail on the MeMo mouse's genetic structure or operation.
IV. Analysis of Infringement Allegations
No probative visual evidence provided in complaint.
- Claim Chart Summary: The complaint’s infringement theory is based on allegations that directly track the language of the asserted claims.
| Claim Element (from Independent Claim 1 and Dependent Claim 9) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A genetically modified mouse, comprising in its germline human unrearranged variable region gene segments inserted at an endogenous mouse immunoglobulin locus | Plaintiff alleges that "Merus has made a genetically modified mouse that comprises, in its germline, at least human unrearranged heavy chain variable region gene segments inserted at an endogenous mouse immunoglobulin locus." | ¶24 | col. 29:38-44 |
| wherein the mouse produces an antibody that comprises a human variable region and a mouse constant region. | Plaintiff alleges that the accused mouse "produces an antibody comprising a human variable region and a mouse constant region." | ¶24 | col. 29:55-65 |
- Identified Points of Contention:
- Factual Questions: The complaint's allegations are made on "information and believes" and directly mirror the claim language. (Compl. ¶24). A central issue will be the factual evidence Plaintiff can produce to demonstrate that the MeMo mouse actually incorporates the specific genetic arrangement required by the claims. The complaint itself does not present technical evidence, such as genetic sequencing data, to substantiate its allegations.
- Scope Questions: The case may present a question of whether the genetic modifications in the MeMo mouse constitute an "insertion at an endogenous mouse immunoglobulin locus" as required by the claims. The patent specification describes this as a "direct, in situ replacement," which may raise a dispute over how precisely the human gene segments must replace their mouse counterparts to fall within the claim scope. (’018 Patent, col. 29:40-41).
V. Key Claim Terms for Construction
The Term: "inserted at an endogenous mouse immunoglobulin locus"
Context and Importance: The location of the inserted human gene segments is critical to the invention's purported benefits. Placement "at an endogenous...locus" is meant to leverage native mouse regulatory elements to ensure proper gene expression, recombination, and B-cell development. The definition of "at" this locus will be central to the infringement analysis.
Intrinsic Evidence for Interpretation:
- Evidence for a Narrower Interpretation: The specification describes the invention as a "direct, in situ replacement of the mouse variable region genes with their human counterparts." (’018 Patent, col. 29:40-41). This language could support an interpretation requiring that the human genes precisely substitute for the mouse genes they are replacing, rather than being inserted elsewhere within the general locus.
- Evidence for a Broader Interpretation: The claim language itself does not include the "direct, in situ replacement" limitation. A party could argue that "inserted at" should be given a broader meaning, covering insertion anywhere within the chromosomal boundaries of the immunoglobulin locus, so long as it is functionally linked to the endogenous constant regions.
The Term: "unrearranged variable region gene segments"
Context and Importance: This term is key to distinguishing the invention from methods that might insert a pre-assembled human variable region gene. The patent claims a system where the mouse's own cellular machinery performs V(D)J recombination on the inserted human gene segments to generate antibody diversity. Whether the genetic material in the MeMo mouse qualifies as "unrearranged" will be a pivotal factual and legal question.
Intrinsic Evidence for Interpretation:
- Evidence for a Narrower Interpretation: The description of replacing mouse VDJ regions with human VDJ regions implies that a functional set of gene segments capable of undergoing recombination is required. (’018 Patent, col. 23:34-36). A defendant might argue this requires a substantially complete repertoire of human V, D, and J segments.
- Evidence for a Broader Interpretation: The claim term itself is not limited by the number or type of "segments." A plaintiff might argue that the insertion of any set of human variable gene segments in their germline (i.e., not yet recombined) configuration meets this limitation, even if the set is not comprehensive.
VI. Other Allegations
- Indirect Infringement: The complaint references 35 U.S.C. § 271 generally but does not plead specific facts to support claims for induced or contributory infringement. (Compl. ¶8). The allegations focus on direct infringement by Defendant Merus for "making, using, selling, offering to sell, and/or importing" the accused mice. (Compl. ¶25).
- Willful Infringement: The complaint alleges that Defendant's infringement is willful, wanton, and deliberate. (Compl. ¶27). The factual basis for this allegation is Defendant's alleged pre-suit knowledge of the patent family. The complaint asserts that Merus cited the '018 Patent's parent patent (U.S. Pat. No. 6,596,541) as prior art during its own patent prosecution and participated in European opposition proceedings concerning a related European patent. (Compl. ¶26).
VII. Analyst’s Conclusion: Key Questions for the Case
- A central issue will be one of evidentiary proof: As the complaint's infringement allegations are made on "information and belief," the case will turn on what factual evidence Regeneron can obtain and present to prove that the Merus MeMo mouse possesses the precise genetic structure recited in the asserted claims.
- A second key issue will be one of claim scope: The dispute may focus on the construction of "inserted at an endogenous mouse immunoglobulin locus." The outcome could depend on whether this requires a precise "in situ replacement" of mouse genes with their human counterparts, as suggested by the specification, or allows for insertion anywhere within the broader locus.
- Finally, a critical question for damages will be willfulness: Did Merus’s alleged knowledge of the parent patent family, derived from its own patent prosecution and European proceedings, establish a duty of care that it consciously disregarded, thereby exposing it to a finding of willful infringement and the potential for enhanced damages?