1:25-cv-13004
Harbour Antibodies BV v. Leveragen Inc
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Harbour Antibodies BV and Harbour Antibodies HCAb BV (Netherlands)
- Defendant: Leveragen, Inc. (Delaware)
- Plaintiff’s Counsel: Hamilton, Brook, Smith & Reynolds, P.C.
- Case Identification: 1:25-cv-13004, D. Mass., 10/14/2025
- Venue Allegations: Venue is alleged to be proper in the District of Massachusetts based on Defendant Leveragen, Inc. having a principal place of business in Woburn, Massachusetts.
- Core Dispute: Plaintiff alleges that Defendant’s transgenic mouse platform for generating single-domain antibodies infringes six patents related to methods and compositions for producing heavy-chain only antibodies in non-human mammals.
- Technical Context: The technology involves genetically engineering mice to produce human heavy-chain only antibodies (HCAbs), which are valuable tools for biopharmaceutical drug discovery due to their unique structural and stability properties.
- Key Procedural History: The complaint alleges that Plaintiff provided Defendant with pre-suit notice of infringement via an email on July 18, 2025, which identified five of the six patents-in-suit and raised concerns about Defendant's business activities. This allegation may form the basis for a claim of willful infringement.
Case Timeline
| Date | Event |
|---|---|
| 2004-07-22 | Priority Date for ’522, ’877, ’524, ’179, and ’970 Patents |
| 2005-07-22 | PCT Application Filing Date (PCT/GB2005/002892) |
| 2010-03-19 | Priority Date for ’655 Patent |
| 2014-12-30 | U.S. Patent No. 8,921,522 Issues |
| 2014-12-30 | U.S. Patent No. 8,921,524 Issues |
| 2016-05-24 | U.S. Patent No. 9,346,877 Issues |
| 2016-05-31 | U.S. Patent No. 9,353,179 Issues |
| 2016-06-14 | U.S. Patent No. 9,365,655 Issues |
| 2021-02-02 | U.S. Patent No. 10,906,970 Issues |
| 2022-05-05 | Defendant's PCT Application (PCT/US2022/027946) Filed |
| 2023-11-09 | Defendant's PCT Application (PCT/US2023/037114) Filed |
| 2025-07-18 | Plaintiff Alleges Pre-Suit Notice of Infringement Sent to Defendant |
| 2025-10-14 | Complaint Filed |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 8,921,522 - "Binding Molecules", issued December 30, 2014
The Invention Explained
- Problem Addressed: While heavy-chain only antibodies (HCAbs) found in species like camelids offer advantages for therapeutic development—such as smaller size and greater stability—they are not naturally produced in humans (Compl. ¶20). The technical challenge is to develop a method for generating fully human HCAbs that can undergo the natural process of in vivo affinity maturation to create high-affinity binding molecules for use in medicine (Compl. ¶21, ¶24; ’970 Patent, col. 1:53-col. 2:22).
- The Patented Solution: The invention provides a method for producing soluble, antigen-specific human antibody domains using a transgenic mouse (Compl. ¶22). The mouse is genetically engineered to contain a "heterologous VH heavy chain locus" which includes human variable (V), diversity (D), and joining (J) gene segments (Compl. ¶25). Critically, the associated heavy chain constant region is modified so it "does not encode a functional CH1 domain" (’522 Patent, cl. 1(a)(ii)). The CH1 domain is necessary for pairing with an antibody light chain; its absence forces the mouse's B cells to produce heavy-chain only antibodies upon being challenged with an antigen (’970 Patent, col. 3:42-46). These antigen-specific VH domains can then be cloned for production (Compl. ¶25).
- Technical Importance: This technology established a platform for the in vivo discovery and maturation of fully human heavy-chain only antibodies, combining the therapeutic advantages of HCAbs with the benefits of natural immune system selection for high affinity and specificity (Compl. ¶27).
Key Claims at a Glance
- The complaint asserts at least independent claim 1 (Compl. ¶92).
- Essential elements of Claim 1 include:
- Immunising a transgenic mouse that expresses a heterologous VH heavy chain locus containing human V, D, and J gene segments.
- The locus's constant region must not encode a functional CH1 domain.
- The locus, upon antigen challenge, must be capable of forming a soluble, heavy chain-only antibody.
- Cloning a VH locus that results from VDJ recombination from an antibody-producing cell of the mouse after affinity maturation.
- Producing the soluble, antigen-specific VH binding domain from the clone.
- The complaint does not explicitly reserve the right to assert dependent claims for this patent.
U.S. Patent No. 9,346,877 - "Binding Molecules", issued May 24, 2016
The Invention Explained
- As a continuation of the application leading to the ’522 Patent, the ’877 Patent addresses the same technical problem and discloses the same solution (Compl. ¶31). The technology is directed to methods of producing soluble, antigen-specific VH binding domains in transgenic mice engineered to lack a functional CH1 domain in their antibody heavy chain locus (Compl. ¶22, ¶25).
Key Claims at a Glance
- The complaint asserts at least independent claim 1 (Compl. ¶98).
- The complaint does not reproduce the text of claim 1 of the ’877 Patent. Analysis of the patent indicates its essential elements include:
- Immunising a transgenic mouse expressing a heterologous VH heavy chain locus with an antigen, wherein the locus contains human V, D, and J gene segments and a constant region that does not encode a functional CH1 domain.
- Isolating an antigen-specific VH domain from the immunised transgenic mouse.
- The complaint does not explicitly reserve the right to assert dependent claims for this patent.
U.S. Patent No. 8,921,524 - "Binding Molecules", issued December 30, 2014
- Patent Identification: U.S. Patent No. 8,921,524, "Binding Molecules", issued December 30, 2014 (Compl. ¶30).
- Technology Synopsis: Belonging to the same family as the ’522 Patent, this patent is also directed to methods of producing soluble, antigen-specific heavy chain only antibodies using transgenic rodents engineered with a modified human heavy chain locus that lacks a functional CH1 domain (Compl. ¶22, ¶25, ¶30).
- Asserted Claims: At least independent claim 1 is asserted (Compl. ¶104).
- Accused Features: The complaint alleges infringement through the use of Defendant's SSM platform to produce soluble, antigen-specific heavy chain only antibodies (Compl. ¶79, ¶104).
U.S. Patent No. 9,353,179 - "Binding Molecules", issued May 31, 2016
- Patent Identification: U.S. Patent No. 9,353,179, "Binding Molecules", issued May 31, 2016 (Compl. ¶32).
- Technology Synopsis: As part of the same patent family, this patent concerns methods for generating antigen-specific heavy chain only antibodies in transgenic rodents whose immune systems are engineered to produce such antibodies (Compl. ¶22, ¶25, ¶32).
- Asserted Claims: At least independent claim 1 is asserted (Compl. ¶110).
- Accused Features: Infringement is alleged based on the use of Defendant's SSM platform to produce antigen-specific heavy chain only antibodies (Compl. ¶80, ¶110).
U.S. Patent No. 10,906,970 - "Methods of making heavy chain only antibodies using transgenic animals", issued February 2, 2021
- Patent Identification: U.S. Patent No. 10,906,970, "Methods of making heavy chain only antibodies using transgenic animals", issued February 2, 2021 (Compl. ¶33).
- Technology Synopsis: This patent, also from the same family, claims methods of producing heavy chain only antibodies by immunizing a transgenic animal that expresses a heterologous heavy chain locus modified to prevent light chain association ('970 Patent, Abstract; Compl. ¶22, ¶25).
- Asserted Claims: At least independent claim 1 is asserted (Compl. ¶115).
- Accused Features: The complaint alleges that the use of Defendant's SSM platform to generate HCAbs constitutes infringement (Compl. ¶78, ¶115).
U.S. Patent No. 9,365,655 - "Soluble heavy-chain only antibodies", issued June 14, 2016
- Patent Identification: U.S. Patent No. 9,365,655, "Soluble heavy-chain only antibodies", issued June 14, 2016 (Compl. ¶34).
- Technology Synopsis: Unlike the other patents-in-suit which focus on methods, this patent claims the transgenic non-human mammal itself (Compl. ¶63, ¶120). The claimed mammal's genome comprises a heterologous heavy chain locus capable of producing soluble heavy-chain only antibodies upon antigen challenge (Compl. ¶63).
- Asserted Claims: At least independent claim 1 is asserted (Compl. ¶120).
- Accused Features: The complaint alleges that Defendant's production, use, and sale of at least the SSV1 mouse, a component of its SSM platform, infringes the ’655 Patent (Compl. ¶81, ¶120).
III. The Accused Instrumentality
Product Identification
The accused instrumentality is Defendant Leveragen's "SSM platform," which includes a "Singularity Sapiens Mouse (SSM)" and its specific variants, SSV1 through SSV6 mice (Compl. ¶41, ¶46).
Functionality and Market Context
The SSM platform is advertised as a system for generating "fully human single-domain antibodies" through in vivo maturation in transgenic mice (Compl. ¶41, ¶43). According to the complaint, Leveragen's marketing materials state the SSM mice "exclusively generate heavy chain antibodies or HCAbs from the complete human VH repertoire integrated into the mouse Igh locus" (Compl. ¶41). The complaint includes a diagram from a Leveragen patent application, illustrating that the accused SSV1-5 mice contain a locus with human VH, DH, and JH gene segments linked to a mouse constant region where the CH1 domain is deleted (Mouse IgG1ACH1) (Compl. ¶60-61). This diagram depicts a structure composed of human variable regions and a mouse constant region, resulting in a chimeric antibody (Compl. ¶60, "Human/Mouse Chimeric Heavy-chain Antibody (HCAb)"). The complaint positions the SSM platform as a direct competitor that "copies and replicates the patented functions" of Plaintiff's HCAb Platform (Compl. ¶44, ¶72).
IV. Analysis of Infringement Allegations
’522 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| a. immunising a transgenic mouse expressing a heterologous VH heavy chain locus with an antigen wherein: | Defendant’s SSM platform involves using its Singularity Sapiens Mouse (SSM), which undergoes "antigen-driven clonal selection and affinity maturation." | ¶41, ¶42 | col. 36:10-12 |
| i. the VH heavy chain locus comprises a variable region comprising at least one naturally occurring human VH gene segment, at least one D gene segment, at least one J gene segment and at least one heavy chain constant region; | The SSM mice allegedly contain an Igh locus with "the complete human VH repertoire," including human VH, DH, and JH gene segments. A diagram from Defendant’s own patent application depicts "Human VHs," "Human DHs," and "Human JHs" in the locus. | ¶41, ¶55, ¶61 | col. 5:10-14 |
| ii. each constant region does not encode a functional CH1 domain; | The constant region in the accused SSM mice is described as "Mouse IgG1ACH1," which the complaint alleges "does not include a CH1 domain." | ¶61, ¶62, ¶67 | col. 3:42-46 |
| iii. the VH gene segment, D gene segment and J gene segment are capable of recombining to form a VDJ coding sequence; | Defendant's website allegedly states that its platform's antibody production "requires recombination of VH, D, and J genes...to create a VDJ coding sequence." | ¶64, ¶65 | col. 3:30-34 |
| iv. the recombined VH heavy chain locus...is capable of forming a soluble, heavy chain-only antibody...devoid of a functional CH1 domain...; | Defendant advertises that its SSM platform produces "Single-domain antibodies" that exhibit "solubility" and are a form of heavy-chain only antibody. | ¶66, ¶67 | col. 3:35-40 |
| b. cloning a VH locus resulting from recombination...from an antibody-producing cell...after affinity maturation...; | Defendant's patent applications allegedly disclose "clonotyping," "cell cloning," and "high throughput cloning" of antibody sequences after the mice undergo "affinity maturation." | ¶42, ¶68, ¶69 | col. 8:12-16 |
| c. producing said soluble, antigen specific VH binding domain from the clone of step b. | Defendant's platform is allegedly used to produce "soluble, antigen-specific VH binding domains or heavy chain only antibodies (HCAb)." | ¶47, ¶69 | col. 8:12-19 |
’877 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| a. immunising a transgenic mouse expressing a heterologous VH heavy chain locus with an antigen wherein...[elements i-iv as above]...; | As alleged for the ’522 Patent, Defendant's platform involves immunizing its SSM mice, which allegedly contain a heterologous human VDJ locus and a constant region lacking a functional CH1 domain, to produce soluble HCAbs. | ¶41, ¶42, ¶61, ¶62, ¶64, ¶67 | col. 36:10-12 |
| b. isolating an antigen-specific VH domain from the immunized transgenic mouse. | The complaint alleges on information and belief that Defendant's platform involves methods to produce (and implicitly isolate) a soluble, antigen-specific VH binding domain. Defendant's materials reference "cloning" and "prioritizing candidates." | ¶42, ¶47, ¶68, ¶70 | col. 7:25-27 |
Identified Points of Contention
- Scope Questions: The claims of the ’522 and ’877 Patents are directed to a multi-step method. A central question may be whether the Defendant, Leveragen, performs all the claimed steps itself, thereby directly infringing. The complaint alleges that the SSM platform is used by "Leveragen and its customers" (Compl. ¶47), which suggests the possibility that infringement may be split between Leveragen (e.g., providing the mice) and its customers (e.g., performing immunization and cloning), raising complex issues of divided and indirect infringement.
- Technical Questions: The infringement theory relies heavily on Defendant's marketing materials and patent applications (Compl. ¶41-43, ¶60-61, ¶68). A primary point of contention will be an evidentiary one: what evidence does the complaint provide, beyond these public documents, that the genetic makeup of the SSV1-6 mice and the actual processes employed by Leveragen and its customers precisely match the claimed elements, particularly the structure of the "Mouse IgG1ACH1" region and the specific steps of "cloning" and "producing" as defined by the patents?
V. Key Claim Terms for Construction
"functional CH1 domain"
Context and Importance
The absence of a "functional CH1 domain" is the core technical feature that enables the production of heavy-chain only antibodies. The definition of this term will be central to determining whether the accused SSM mice, which allegedly contain a "Mouse IgG1ACH1" region (Compl. ¶61), meet this claim limitation.
Intrinsic Evidence for a Broader Interpretation
The specification explains that the purpose of the CH1 domain is to facilitate interaction with the antibody light chain ('970 Patent, col. 3:35-40). Language stating the invention provides a heavy chain "which lacks a CH1 domain and is therefore unable to associate with an immunoglobulin light chain" ('970 Patent, col. 4:44-46) may support an interpretation where any modification that renders the CH1 region unable to perform this binding function makes it non-"functional."
Intrinsic Evidence for a Narrower Interpretation
Embodiments in the patent figures are labeled with notations like "CY2ACH1," where "A" may imply deletion ('970 Patent, Fig. 6). This could support an argument that "devoid of a functional CH1 domain" requires the complete absence or deletion of the CH1 exon, not merely its modification.
"cloning a VH locus"
Context and Importance
This is an active step in method claim 1 of the ’522 Patent. The interpretation of "cloning" will be critical to determining if the actions taken by Leveragen or its customers constitute infringement of this step. Practitioners may focus on this term because modern antibody discovery can involve high-throughput sequencing and synthesis rather than traditional molecular cloning.
Intrinsic Evidence for a Broader Interpretation
The patent mentions that monoclonal antibodies can be recovered "by standard cloning technology or recovered from B-cell mRNA by phage display technology" ('970 Patent, col. 4:51-54). This suggests "cloning" is not limited to a single specific technique and could be interpreted to cover a range of methods for isolating and replicating the genetic information of the VH locus.
Intrinsic Evidence for a Narrower Interpretation
A party might argue that in the context of the patent's filing date, "cloning" refers to the well-understood molecular biology process of physically isolating a DNA fragment and inserting it into a plasmid or other vector. Leveragen's alleged use of "clonotyping" or "high throughput cloning" (Compl. ¶68) may or may not map onto this more traditional definition.
VI. Other Allegations
Indirect Infringement
The complaint alleges that Leveragen induces infringement by its customers (Compl. ¶74, ¶83, ¶93). The factual basis for this allegation is Leveragen's advertisement, sale, and promotion of its SSM platform, as well as its alleged provision of "instructions, guidance, and direction" to customers on how to use the platform to generate HCAbs, which allegedly constitutes the patented method (Compl. ¶82-83).
Willful Infringement
The willfulness allegation is based on alleged pre-suit knowledge of the patents-in-suit (Compl. ¶89). The complaint provides a specific factual basis: an email allegedly sent by Plaintiff to Defendant on July 18, 2025, which identified several of the patents and expressed concerns regarding Leveragen's business (Compl. ¶86).
VII. Analyst’s Conclusion: Key Questions for the Case
- A core issue will be one of divided infringement: does Leveragen's business model involve performing all steps of the asserted method claims, or does it only perform some steps while encouraging its customers to perform others? The resolution of this question will determine whether the primary infringement theory rests on direct infringement by Leveragen or indirect infringement through the actions of its customers.
- A key evidentiary question will be one of technical proof: can the Plaintiff demonstrate through discovery that the genetic architecture of the accused SSM mice—particularly the "ACH1" constant region—and the precise biochemical processes used in the SSM platform align with the specific limitations of the asserted claims, moving beyond the allegations currently based on Leveragen's marketing and patent application materials?
- A central legal question will be one of definitional scope: can the term "devoid of a functional CH1 domain" be construed to cover a modified or truncated CH1 region that still exists but cannot bind a light chain, or does it narrowly require the complete deletion of the CH1 exon, potentially creating a non-infringement argument for the accused "ACH1" construct?