DCT
3:20-cv-00171
Regenxbio Inc. et
Key Events
Complaint
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: REGENXBIO Inc. (Delaware) and The Trustees of the University of Pennsylvania (Pennsylvania)
- Defendant: Aldevron LLC (North Dakota)
- Plaintiff’s Counsel: Jones Day; Serkland Law Firm
- Case Identification: 3:20-cv-00171, D.N.D., 09/16/2020
- Venue Allegations: Venue is asserted based on Defendant Aldevron being organized and having its principal place of business in North Dakota, thus being domiciled in the district.
- Core Dispute: Plaintiffs allege that Defendant’s contract manufacturing of plasmids containing genetic sequences for the adeno-associated virus serotype 8 (AAV8) capsid protein infringes a patent covering the engineered host cells used in that manufacturing process.
- Technical Context: The technology relates to the production of components for AAV vectors, which are critical delivery vehicles for the rapidly growing field of gene therapy.
- Key Procedural History: The complaint details a complex licensing history establishing Plaintiffs' rights to the patent-in-suit. The University of Pennsylvania, the original assignee, granted an exclusive license to GlaxoSmithKline (GSK) in 2002, and later granted an exclusive license to REGENXBIO in 2009. REGENXBIO also received an exclusive license from GSK in 2009. GSK subsequently assigned its infringement claims against Aldevron to REGENXBIO, consolidating the rights necessary to bring this suit.
Case Timeline
| Date | Event |
|---|---|
| 2001-12-17 | Earliest Priority Date for ’435 Patent |
| 2002-05-31 | University grants exclusive license to GSK |
| 2009-02-24 | University grants exclusive license to REGENXBIO |
| 2009-03-06 | GSK grants exclusive license to REGENXBIO |
| 2011-01-18 | Earliest identified date of alleged infringing activity by Aldevron |
| 2020-03-17 | ’435 Patent issues |
| 2020-09-16 | Complaint filed |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 10,590,435 - "Adeno-associated virus (AAV) serotype 8 sequences, vectors containing same, and uses therefor"
- Patent Identification: U.S. Patent No. 10,590,435, titled “Adeno-associated virus (AAV) serotype 8 sequences, vectors containing same, and uses therefor,” issued on March 17, 2020.
The Invention Explained
- Problem Addressed: The complaint explains that prior to the inventors’ work, only a small number of AAV serotypes were known, and discovering novel serotypes was "extraordinarily difficult" due to the virus’s low abundance in tissue samples (Compl. ¶30). The patent notes a general need for more desirable AAV-based constructs for gene delivery (’435 Patent, col. 2:7-8).
- The Patented Solution: The inventors bypassed the difficulty of isolating whole viruses by using PCR-based methods to directly amplify AAV capsid gene sequences from tissue, leading to the discovery of many new serotypes, including AAV8 (Compl. ¶31). The ’435 Patent claims a key tool for manufacturing AAV components: a cultured host cell that contains a man-made "recombinant nucleic acid molecule" (such as a plasmid) that both (1) codes for the AAV8 capsid protein and (2) includes a "heterologous non-AAV sequence," like a standard plasmid backbone (’435 Patent, Claim 1; Compl. ¶¶ 21, 32). These engineered cells are used as factories to produce large quantities of plasmids needed for generating AAV vectors.
- Technical Importance: The complaint asserts that the resulting AAV8 vector offers significant advantages, including "higher gene transfer, longer-term gene expression, broad and novel tissue selectivity, lower immune response, and improved manufacturability," making it a highly valuable tool in the gene therapy field (Compl. ¶31).
Key Claims at a Glance
- The complaint asserts independent claims 1 and 7 (Compl. ¶51).
- Independent Claim 1 recites:
- A cultured host cell
- Containing a recombinant nucleic acid molecule
- That encodes an AAV vp1 capsid protein with a sequence from SEQ ID NO: 2 (AAV8) or a sequence at least 95% identical thereto
- Wherein the nucleic acid molecule also comprises a heterologous non-AAV sequence.
- Independent Claim 7 recites:
- A cultured host cell
- Containing a recombinant nucleic acid molecule
- That comprises a specific nucleotide sequence from SEQ ID NO: 1 (or a sequence at least 95% identical thereto) corresponding to certain parts of the AAV8 gene (vp1, vp2, or vp3)
- Wherein the nucleic acid molecule also comprises a heterologous non-AAV sequence.
- The complaint alleges infringement of at least one claim of the ’435 Patent (Compl. ¶55).
III. The Accused Instrumentality
Product Identification
- The accused instrumentalities are the "cultured host cells" that Defendant Aldevron allegedly makes and uses as part of its contract manufacturing services for producing plasmids (Compl. ¶¶ 1, 55). These cells contain recombinant DNA that encodes AAV8 capsid proteins.
Functionality and Market Context
- The complaint identifies Aldevron as a "leading contract manufacturer of plasmids" that produces research-grade, GMP-Source®, and cGMP grade plasmids for its customers (Compl. ¶¶ 35-36). The accused process involves Aldevron taking a customer's plasmid containing an AAV8 capsid gene, introducing it into host cells (e.g., E. coli), and then culturing those host cells to create large quantities of the plasmid (Compl. ¶¶ 26, 37). The complaint provides a diagram illustrating this process of using host cells to create amplified plasmids (Compl. p. 8). Aldevron is also alleged to create and store "Master Cell Bank[s]" of these infringing cultured host cells (Compl. ¶42(b)). These services are alleged to be used by third-party gene therapy companies not authorized by Plaintiffs to use the AAV8 technology (Compl. ¶41-42).
IV. Analysis of Infringement Allegations
The infringement allegations center on Aldevron's process of using cultured bacterial cells to mass-produce plasmids containing the AAV8 capsid gene for its customers. The complaint provides a diagram depicting the creation of a "Master Cell Bank containing AAV8 cap plasmids" and subsequent amplification, which directly illustrates the allegedly infringing activity (Compl. p. 13).
’435 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A cultured host cell... | Aldevron allegedly uses cultured host cells, such as E. coli, to replicate and manufacture plasmids. The complaint alleges Aldevron prepares and stores "Master Cell Bank[s]" of these cultured host cells. | ¶¶ 36, 37, 42(b) | col. 7:49-56 |
| ...containing a recombinant nucleic acid molecule encoding an AAV vp1 capsid protein having a sequence comprising amino acids 1 to 738 of SEQ ID NO: 2 (AAV8) or a sequence at least 95% identical... | Aldevron is alleged to manufacture plasmids for third parties that contain the AAV8 cap gene. The complaint specifically alleges Aldevron's cultured host cells contain a plasmid that encodes an AAV capsid protein with a sequence at least 95% identical to SEQ ID NO: 2. | ¶¶ 42(a-d), 52 | col. 6:2-4 |
| ...wherein the recombinant nucleic acid molecule further comprises a heterologous non-AAV sequence. | The plasmids used by Aldevron allegedly contain the AAV8 cap gene within a larger plasmid "backbone" that includes non-AAV sequences, such as those required for replication in host cells. | ¶¶ 21, 41, 52 | col. 5:9-12 |
- Identified Points of Contention:
- Scope Questions: The claims are directed to a "cultured host cell," a composition of matter. Aldevron's business is providing a plasmid manufacturing service. A potential dispute is whether Aldevron's alleged activities—which include creating, culturing, storing in cell banks, and ultimately lysing the host cells to harvest plasmids—constitute infringing "making" and "using" of the claimed cell. Aldevron may argue that its use is a transient, non-infringing step in an unpatented manufacturing process.
- Technical Questions: The complaint alleges on "information and belief," supported by public documents, that Aldevron manufactures materials for third parties containing the AAV8 capsid sequence (Compl. ¶42). A key evidentiary question will be whether discovery confirms that the materials made by Aldevron actually contain nucleic acid or amino acid sequences meeting the specific "at least 95% identical" limitations of the asserted claims.
V. Key Claim Terms for Construction
The Term: "cultured host cell"
Context and Importance: This term defines the invention itself. The infringement analysis may turn on whether Aldevron's activities—particularly the transient culturing of bacterial cells for plasmid amplification and the creation of master cell banks—fall within the scope of this term. Practitioners may focus on this term because its construction determines if Aldevron's core service offering directly infringes the claim, or if it is merely an unpatented process that uses the claimed composition as a non-infringing intermediate.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The patent specification refers to a wide range of host cells, including prokaryotic cells like E. coli, which are commonly used for plasmid amplification (’435 Patent, col. 15:21-31). Plaintiffs may argue the plain and ordinary meaning covers any such cell that has been cultured, regardless of whether its use is transient or for a final product.
- Evidence for a Narrower Interpretation: The patent also describes using host cells to produce rAAV particles for gene therapy, a more complex process than simple plasmid amplification (’435 Patent, col. 8:5-15). A defendant might argue that the term, in the context of the full specification, should be limited to cells used for producing viral vectors, not just for amplifying DNA in bacteria.
The Term: "heterologous non-AAV sequence"
Context and Importance: This limitation distinguishes the claimed recombinant molecule from a naturally occurring AAV genome. Its construction is critical, as a broad reading would likely cover any standard plasmid backbone. Practitioners may focus on this term because if it is read broadly, it may be easily met by Aldevron's alleged use of standard cloning plasmids.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification describes creating artificial vectors using sequences from a "non-AAV viral source, or from a non-viral source" (’435 Patent, col. 5:9-12). This language supports a broad interpretation where "heterologous" means any sequence not native to AAV, which would include typical plasmid elements like antibiotic resistance genes and origins of replication.
- Evidence for a Narrower Interpretation: A defendant could argue that the term should be limited to sequences that impart a specific viral function, such as altering tropism, rather than standard manufacturing-related sequences. The specification’s discussion of creating "chimeric" and "humanized" capsids could be cited to support an argument that the term implies more than just a generic plasmid backbone (’435 Patent, col. 5:13-15).
VI. Other Allegations
Willful Infringement
- While the complaint does not include a separate count for "willful infringement," the prayer for relief requests a declaration that the case is "exceptional" and an award of "treble damages" under 35 U.S.C. § 285 (Compl., p. 22, ¶D). The allegations supporting this request appear to be based on Aldevron's alleged continuation of infringing activities after the ’435 Patent issued on March 17, 2020 (Compl. ¶34). The complaint also notes that REGENXBIO has ordered plasmids from Aldevron, which may be used to suggest Aldevron had knowledge of Plaintiffs' technology portfolio (Compl. ¶40).
VII. Analyst’s Conclusion: Key Questions for the Case
This case appears poised to address fundamental questions about where patent protection begins and ends in the complex supply chain of modern biologic drug manufacturing. The key questions for the court will likely be:
- A core issue will be one of definitional scope: Is a contract manufacturer's transient use of "cultured host cells" as an intermediate factory for plasmid DNA an act of direct infringement on claims to the cells themselves, or is it an unpatented manufacturing process? The plaintiffs' allegations regarding Aldevron's creation and storage of master cell banks will be a critical factual component of this dispute.
- A second key issue will be one of evidentiary proof: Can Plaintiffs obtain evidence through discovery to demonstrate that the specific materials Aldevron manufactured for its clients meet the precise sequence identity thresholds (e.g., >95% identity) required by the asserted patent claims?
- Finally, the case raises a question of remedy and conduct: Given the patent's recent issuance, the dispute will focus on post-issuance activities. A central question will be whether Aldevron’s conduct, should infringement be found, was sufficiently egregious to be deemed "exceptional" and warrant the enhancement of damages.