Fate Therap Inc v. Shoreline Biosciences Inc

I. Executive Summary and Procedural Information

• Parties & Counsel:
  • Plaintiff: Fate Therapeutics, Inc. (Delaware) and Whitehead Institute for Biomedical Research (Delaware)
  • Defendant: Shoreline Biosciences, Inc. (Delaware) and Dan S. Kaufman (California)
  • Plaintiff’s Counsel: Greenberg Traurig, LLP
• Case Identification: 3:22-cv-00676, S.D. Cal., 05/13/2022
• Venue Allegations: Venue is alleged to be proper as Defendants reside in and/or have a regular and established place of business in the Southern District of California.
• Core Dispute: Plaintiffs allege that Defendants’ platform for manufacturing induced pluripotent stem cell (iPSC)-derived immunotherapies infringes six patents related to fundamental compositions and methods for reprogramming somatic cells.
• Technical Context: The technology concerns the creation of induced pluripotent stem cells (iPSCs), which are foundational for developing "off-the-shelf" cell therapies for diseases such as cancer.
• Key Procedural History: The complaint alleges that Defendant Dr. Kaufman, while serving as a paid Scientific Advisor to Plaintiff Fate Therapeutics under an exclusivity agreement, co-founded Defendant Shoreline Biosciences to directly compete with Fate Therapeutics by using Plaintiffs' patented iPSC platform. This alleged history forms the basis for claims of willful infringement.

Case Timeline

Date	Event
2003-11-26	Priority Date for all Asserted Patents
2011-12-06	U.S. Patent No. 8,071,369 Issues
2015-01-13	U.S. Patent No. 8,932,856 Issues
2015-01-27	U.S. Patent No. 8,940,536 Issues
2015-02-10	U.S. Patent No. 8,951,797 Issues
2015-07-01	Dr. Kaufman's Scientific Advisor agreement with Fate Therapeutics begins
2015-10-27	U.S. Patent No. 9,169,490 Issues
2019-10-29	U.S. Patent No. 10,457,917 Issues
2020-05-14	Shoreline Biosciences allegedly co-founded by Dr. Kaufman
2022-05-13	Complaint Filed

II. Technology and Patent(s)-in-Suit Analysis

U.S. Patent No. 8,071,369 - "Compositions for Reprogramming Somatic Cells"

• Patent Identification: U.S. Patent No. 8,071,369, issued December 6, 2011 (’369 Patent).

The Invention Explained

• Problem Addressed: The patent describes a need for alternative methods of generating pluripotent stem cells that do not rely on controversial sources like embryos or involve mixing materials from multiple species (’369 Patent, col. 2:5-17).
• The Patented Solution: The invention provides compositions and methods for reprogramming differentiated somatic cells (i.e., common body cells) into a less-differentiated, pluripotent state, similar to embryonic stem cells (’369 Patent, Abstract). The core of the solution is the introduction of a pluripotency gene, such as Oct4, into a somatic cell to trigger this reprogramming (’369 Patent, col. 2:18-32).
• Technical Importance: This technology is foundational to the field of induced pluripotent stem cells (iPSCs), enabling the creation of patient-specific or universal "master cell lines" for therapeutic development without the ethical and immunological barriers associated with embryonic stem cells (Compl. ¶2, ¶30).

Key Claims at a Glance

• The complaint asserts independent claim 1 (Compl. ¶70).
• Claim 1 requires:
  • A composition comprising an isolated primary somatic cell
  • that comprises an exogenously introduced nucleic acid encoding an Oct4 protein
  • operably linked to at least one regulatory sequence.
• The complaint alleges infringement of "at least claim 1," thereby reserving the right to assert other claims (Compl. ¶68).

U.S. Patent No. 8,932,856 - "Methods for Reprogramming Somatic Cells"

• Patent Identification: U.S. Patent No. 8,932,856, issued January 13, 2015 (’856 Patent).

The Invention Explained

• Problem Addressed: As the ’856 Patent shares a common specification with the ’369 Patent, it addresses the same problem of needing non-controversial sources for pluripotent stem cells (’856 Patent, col. 2:5-17).
• The Patented Solution: This patent claims a method for making a somatic cell "more susceptible to reprogramming" (’856 Patent, Abstract). The method involves introducing an exogenous nucleic acid that encodes the Oct4 protein into the cell. This introduction increases the expression of Oct4 protein, which in turn makes the cell more amenable to being reprogrammed into a pluripotent state (’856 Patent, col. 19:40-47).
• Technical Importance: The method provides a way to "prime" or prepare somatic cells for the difficult process of reprogramming, a key step in controllably and efficiently generating iPSCs for therapeutic applications (Compl. ¶2, ¶30).

Key Claims at a Glance

• The complaint asserts independent claim 1 (Compl. ¶97).
• Claim 1 requires:
  • A method of making a somatic cell more susceptible to reprogramming to a pluripotent state
  • comprising introducing at least one exogenous nucleic acid encoding Oct4 operably linked to at least one regulatory sequence into the cell,
  • thereby increasing expression of Oct4 protein in the somatic cell,
  • wherein increased expression of Oct4 protein makes the cell more susceptible to reprogramming to a pluripotent state.
• The complaint alleges infringement of "at least claim 1" (Compl. ¶95).

U.S. Patent No. 8,951,797 - "Compositions for Identifying Reprogramming Factors"

• Patent Identification: 8,951,797, issued February 10, 2015 (’797 Patent).
• Technology Synopsis: This patent claims a composition comprising an isolated primary somatic cell into which an exogenous nucleic acid encoding Oct4 has been introduced, with the specific functional requirement that this introduction "increases Oct4 expression in the cell" (Compl. ¶127). This links the claimed composition directly to a functional outcome of gene expression.
• Asserted Claims: Claim 1 (Compl. ¶127).
• Accused Features: The complaint alleges that Defendants' iPSC manufacturing platform creates cells that meet the limitations of this composition claim (Compl. ¶128-131).

U.S. Patent No. 8,940,536 - "Methods for Making Somatic Cells More Susceptible to Reprogramming"

• Patent Identification: 8,940,536, issued January 27, 2015 (’536 Patent).
• Technology Synopsis: This patent claims a method of making a primary somatic cell more susceptible to reprogramming by introducing an exogenous nucleic acid for Oct4 (Compl. ¶154). The claim requires that the resulting expression of this introduced nucleic acid makes the cell more susceptible to reprogramming. This method is similar to that of the ’856 Patent but is specifically directed to "primary" somatic cells.
• Asserted Claims: Claim 1 (Compl. ¶154).
• Accused Features: Defendants' iPSC manufacturing process is accused of practicing this method, as it allegedly starts with primary somatic cells and introduces the Oct4 gene to facilitate reprogramming (Compl. ¶156, ¶158).

U.S. Patent No. 9,169,490 - "Methods for Reprogramming Somatic Cells"

• Patent Identification: 9,169,490, issued October 27, 2015 (’490 Patent).
• Technology Synopsis: This patent claims a composition comprising a somatic cell with an exogenous nucleic acid for Oct4, adding the quantitative limitation that the resulting "amount of Oct4 expression [is] comparable to the amount of Oct4 expression in an embryonic stem cell" (Compl. ¶184). This ties the claimed composition to a functional benchmark characteristic of pluripotent cells.
• Asserted Claims: Claim 1 (Compl. ¶184).
• Accused Features: The complaint accuses the iPSCs generated by Defendants' platform, which, to be pluripotent, would necessarily exhibit Oct4 expression levels comparable to embryonic stem cells (Compl. ¶188).

U.S. Patent No. 10,457,917 - "Methods for Reprogramming Somatic Cells"

• Patent Identification: 10,457,917, issued October 29, 2019 (’917 Patent).
• Technology Synopsis: This patent claims a method of making a somatic cell more susceptible to reprogramming by increasing Oct4 expression, similar to the ’856 and ’536 patents. However, it adds the specific process limitation that "the exogenous nucleic acid is transiently transfected into the somatic cell" (Compl. ¶211). This distinguishes the method from processes that permanently integrate the gene into the cell's genome.
• Asserted Claims: Claim 1 (Compl. ¶211).
• Accused Features: The complaint alleges on information and belief that Defendants' method involves transiently transfecting somatic cells with the Oct4-encoding nucleic acid (Compl. ¶213).

III. The Accused Instrumentality

• Product Identification: The accused instrumentality is Defendants’ "iPSC-derived cell therapy manufacturing platform" (Compl. ¶71). This platform is used to create "off-the-shelf" allogeneic natural killer (NK) and other immunotherapy cells derived from induced pluripotent stem cells (Compl. ¶6, ¶8).
• Functionality and Market Context: The complaint alleges that the accused platform starts with isolated primary somatic cells, such as human fibroblasts, and reprograms them into iPSCs (Compl. ¶72). This reprogramming is allegedly achieved by introducing an exogenous nucleic acid encoding the Oct4 protein (Compl. ¶72). A diagram in the complaint illustrates a multi-step process that starts with generating an iPSC, creating a master clone through genetic manipulation, and expanding it into a homogenous population of functional immune cells for therapeutic use (Compl., p. 15). The complaint alleges this platform enabled Defendants to secure strategic partnerships and funding valued at over $4 billion, positioning them as a direct competitor to Plaintiffs (Compl. ¶8, ¶10).

IV. Analysis of Infringement Allegations

8,071,369 Patent Infringement Allegations

Claim Element (from Independent Claim 1)	Alleged Infringing Functionality	Complaint Citation	Patent Citation
A composition comprising an isolated primary somatic cell	Defendants allegedly generate iPSCs by starting with isolated primary somatic cells, such as human skin cells or fibroblasts.	¶72	col. 6:6-14
that comprises an exogenously introduced nucleic acid encoding an Oct4 protein	To reprogram these cells, Defendants allegedly introduce a foreign nucleic acid, such as cDNA, that contains the code for the Oct4 protein.	¶72, ¶74	col. 2:28-32
operably linked to at least one regulatory sequence.	The introduced nucleic acid for Oct4 is allegedly linked to a regulatory sequence that controls its expression within the somatic cell.	¶72, ¶74	col. 19:38-45

8,932,856 Patent Infringement Allegations

Claim Element (from Independent Claim 1)	Alleged Infringing Functionality	Complaint Citation	Patent Citation
A method of making a somatic cell more susceptible to reprogramming to a pluripotent state	Defendants' "iPSC-derived cell therapy manufacturing platform" is alleged to be a method for creating iPSCs, a process that inherently involves making somatic cells susceptible to reprogramming. The complaint includes a diagram outlining the accused manufacturing process (Compl., p. 19).	¶98	col. 10:1-12
comprising introducing at least one exogenous nucleic acid encoding Oct4 operably linked to at least one regulatory sequence into the cell,	The method allegedly includes the step of introducing an external nucleic acid (like cDNA) for Oct4, which is linked to a regulatory sequence to drive its expression, into the starting somatic cells.	¶99, ¶101	col. 10:43-52
thereby increasing expression of Oct4 protein in the somatic cell,	The introduction of this nucleic acid allegedly results in an increased amount of Oct4 protein within the cell, a key trigger for reprogramming.	¶99, ¶101	col. 10:53-57
wherein increased expression of Oct4 protein makes the cell more susceptible to reprogramming to a pluripotent state.	The complaint alleges that this increased expression of Oct4 is the mechanism that makes the somatic cell more susceptible to being converted into a pluripotent stem cell.	¶99, ¶101	col. 10:57-60

• Identified Points of Contention:
  • Evidentiary Questions: The complaint's allegations regarding the specific steps of Defendants' proprietary process are made "on information and belief." A central point of contention will be whether discovery confirms that Defendants' platform actually performs each claimed step as alleged. For example, what is the precise nature of the starting cells, the nucleic acid vector used, and the method of introduction (e.g., transient vs. stable transfection, as implicated by the ’917 Patent)?
  • Scope Questions: The asserted patents claim priority to 2003 and describe foundational iPSC technology. A potential dispute may arise over whether Defendants' process, which Dr. Kaufman allegedly described as "using new technology" (Compl. ¶46), incorporates technical advances that place it outside the scope of the patents' claims as they would have been understood at the time of the invention. For the method claims, contention may arise over whether the functional result of making a cell "more susceptible to reprogramming" is achieved in the specific manner claimed.

V. Key Claim Terms for Construction

• The Term: "primary somatic cell" (’369 Patent, Claim 1)

• Context and Importance: This term defines the starting material for the claimed composition. Its construction is critical because infringement of this claim may depend on whether Defendants begin their process with cells taken directly from a donor ("primary") or with an established, immortalized cell line.

• Intrinsic Evidence for Interpretation:

  • Evidence for a Broader Interpretation: The specification provides a broad definition of "somatic cells," stating they may be "primary cells (non-immortalized cells)...or may be derived from a cell line (immortalized cells)" (’369 Patent, col. 6:6-14). A party could argue this context suggests "primary" should not be read as a strict limitation excluding all cell lines.
  • Evidence for a Narrower Interpretation: The explicit inclusion of the word "primary" in Claim 1, while the specification discusses both cell types, may suggest a deliberate choice to limit the scope of this specific claim to non-immortalized cells. A party could argue this constitutes a specific claim differentiation from other potential claims covering any somatic cell.

• The Term: "more susceptible to reprogramming" (’856 Patent, Claim 1)

• Context and Importance: This functional language is a required outcome of the claimed method. The dispute will likely center on what evidence is needed to prove that the introduction of Oct4, rather than other factors, is what makes the cell "more susceptible" and how that increased susceptibility is defined and measured.

• Intrinsic Evidence for Interpretation:

  • Evidence for a Broader Interpretation: The claim language itself links the "increased expression of Oct4 protein" directly to the outcome of making the cell "more susceptible" (’856 Patent, Claim 1). Plaintiffs may argue that because Oct4 is a master regulator of pluripotency, this functional result is an inherent and necessary consequence of its increased expression, as taught by the patent.
  • Evidence for a Narrower Interpretation: A defendant could argue that "more susceptible" requires a quantifiable increase in reprogramming efficiency relative to a defined baseline. They might also contend that their process uses a combination of factors (as suggested by the mention of other genes in Compl. ¶31) and that Oct4 expression alone does not achieve the claimed functional result in the manner described by the patent.

VI. Other Allegations

• Indirect Infringement: The complaint alleges inducement of infringement under 35 U.S.C. § 271(b). The factual basis is Defendants' alleged partnership with the Advanced Cell Therapy Laboratory (ACTL) of UC San Diego, which Defendants allegedly "instructed and/or supervised" to produce the infringing iPSCs (Compl. ¶81, ¶108, ¶138).
• Willful Infringement: Willfulness is alleged based on Dr. Kaufman's pre-suit knowledge of the Asserted Patents, which he allegedly gained during his time as a Scientific Advisor for Fate Therapeutics (Compl. ¶79, ¶106). The complaint alleges that Defendants' infringement was a deliberate choice to compete with Fate using its own patented technology, which may support a finding of egregious conduct (Compl. ¶86, ¶116).

VII. Analyst’s Conclusion: Key Questions for the Case

• A core issue will be one of evidentiary confirmation: The complaint is premised on "information and belief" that Defendants' platform, which was allegedly touted as "new technology," practices foundational methods for creating iPSCs patented over a decade ago. The case may turn on whether discovery uncovers direct evidence—such as internal protocols, lab notebooks, or source code for cell engineering—that proves Defendants' proprietary process maps onto the specific elements of the asserted claims.
• A second central question will be one of knowledge and intent: Given the specific allegations about Dr. Kaufman's prior relationship with Fate Therapeutics, a key focus will be whether his alleged knowledge of the patents-in-suit can be imputed to Shoreline to establish willful infringement. This will likely involve a factual inquiry into the scope of his advisory role at Fate, his awareness of the specific patented technology, and the timeline of his activities in co-founding a direct competitor.