DCT
1:19-cv-02316
Wilson Wolf Mfg Corp v. Sarepta Therap Inc
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Wilson Wolf Manufacturing Corporation (Minnesota)
- Defendant: Sarepta Therapeutics, Inc. (Delaware)
- Plaintiff’s Counsel: Morris James LLP; Padmanabhan & Dawson, PLLC.
- Case Identification: 1:19-cv-02316, D. Del., 04/23/2020
- Venue Allegations: Venue is alleged to be proper in the District of Delaware because the Defendant is a Delaware corporation and therefore resides in the district.
- Core Dispute: Plaintiff alleges that Defendant’s use of the Corning HYPERStack cell culture device to manufacture viral vectors for gene therapy products infringes patents related to methods and devices for high-efficiency cell culturing.
- Technical Context: The technology concerns devices for culturing cells at high density, a critical process for the large-scale manufacturing of biopharmaceuticals such as monoclonal antibodies and gene therapies.
- Key Procedural History: The complaint is a First Amended Complaint. A central legal issue raised is the applicability of the 35 U.S.C. § 271(e)(1) "Safe Harbor," with the Plaintiff alleging that Defendant's activities were undertaken for commercialization purposes and thus fall outside this statutory exemption from infringement.
Case Timeline
| Date | Event |
|---|---|
| 2003-10-08 | Priority Date for ’192 and ’443 Patents |
| 2014-04-15 | U.S. Patent No. 8,697,443 Issues |
| 2016-09-13 | U.S. Patent No. 9,441,192 Issues |
| 2018 | Sarepta enters manufacturing partnership with Brammer Bio |
| 2019 | Sarepta enters license agreement with Roche |
| 2019 | Sarepta presentation allegedly reflects use of HYPERStack |
| 2020-04-23 | First Amended Complaint Filed |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 9,441,192 - “Cell culture methods and devices utilizing gas permeable materials,” issued September 13, 2016
The Invention Explained
- Problem Addressed: The patent addresses the inefficiency of conventional cell culture flasks, which require a very thin layer of liquid medium (2-3 mm) to allow for oxygen diffusion from a large volume of overlying gas, known as "headspace" (Compl. ¶¶ 13-14). This design wastes the majority of the flask's volume, necessitates frequent and labor-intensive medium changes, and increases the risk of contamination (Compl. ¶¶ 16-17; ’192 Patent, col. 2:1-17).
- The Patented Solution: The invention challenges the conventional wisdom that liquid medium depth must be minimal (Compl. ¶18). It proposes a static cell culture device with at least one gas-permeable surface that is in contact with the ambient atmosphere. This allows oxygen to be supplied from outside the device, eliminating the need for internal headspace and enabling the use of a much greater depth of liquid medium—specifically, beyond 2.0 cm—to support cell growth for longer periods (Compl. ¶18; ’192 Patent, Abstract, col. 17:7-16).
- Technical Importance: This approach allows for culturing a higher density of cells within a given footprint, reducing labor, incubator space, and contamination risk, which are critical factors for scaling up the production of biopharmaceuticals (Compl. ¶18).
Key Claims at a Glance
- The complaint asserts independent claim 1 (Compl. ¶¶ 21, 35).
- The essential elements of independent claim 1 are:
- A method of culturing cells comprising:
- adding medium and animal cells into a static cell culture device that is not compartmentalized by a semi-permeable membrane,
- at least a portion of the device is comprised of a non-porous gas permeable material in contact with ambient gas,
- placing the device in a suitable cell culture location,
- orienting the device so that cells reside upon the gas permeable material,
- wherein the uppermost location of the medium is elevated beyond 2.0 cm from its lowermost location, and
- the device is in a state of static cell culture.
U.S. Patent No. 8,697,443 - “Cell culture methods and devices utilizing gas permeable materials,” issued April 15, 2014
The Invention Explained
- Problem Addressed: The patent addresses the challenge of increasing the surface area for adherent cell growth to scale up production. Conventional multi-shelf devices increase surface area but remain inefficient because each shelf requires its own gas-liquid interface for oxygenation, limiting the overall cell density and device compactness (’443 Patent, col. 13:10-25).
- The Patented Solution: The invention discloses a cell culture device containing at least two stacked growth surfaces, or "scaffolds," where the device itself is comprised at least in part of a gas-permeable material (’443 Patent, Abstract). This design allows gas exchange to occur for all scaffolds simultaneously from outside the device, eliminating the need for an internal gas-liquid interface for each layer. This enables the device to be filled with liquid medium, significantly increasing the cell growth capacity within a given volume (Compl. ¶19; ’443 Patent, col. 16:46-51, Fig. 11).
- Technical Importance: By enabling the integration of multiple growth scaffolds in a compact, medium-filled device without perfusion, the invention provides a method for achieving high-density adherent cell culture suitable for industrial-scale manufacturing (Compl. ¶19).
Key Claims at a Glance
- The complaint asserts infringement of the ’443 Patent and details the elements of claim 26 in its infringement chart (Compl. ¶¶ 36, 40).
- The essential elements of independent claim 26 are:
- A method of culturing cells in a device having a gas permeable material, at least one access port, and at least two scaffolds, the method comprising:
- a) adding cells and liquid medium into the device;
- b) orienting the device so scaffolds are at different elevations;
- c) allowing cells to settle on the scaffolds;
- d) adding enough liquid medium to prevent a gas-liquid interface from forming directly above at least one scaffold;
- e) placing the device in a suitable cell culture location where ambient gas contacts the gas permeable material; and
- f) not perfusing the liquid medium.
III. The Accused Instrumentality
Product Identification
- The accused instrumentality is the process of manufacturing cells and cell-derived products (such as viral vectors for the SRP-9001 gene therapy) through the use of the Corning HYPERStack cell culture device (Compl. ¶¶ 24, 28-29, 41).
Functionality and Market Context
- The HYPERStack is described as a "multiple-shelf" or "multilayered" static cell culture device that utilizes a gas-permeable film for oxygenation (Compl. ¶¶ 24, 36). According to documents cited in the complaint, the device functions via "air spaces ... beneath each culture chamber which is open to the atmosphere," a design which allegedly eliminates the need for internal "headspace" for gas exchange (Compl. ¶¶ 35-36). A diagram included in the complaint illustrates a single layer of the device, showing cells on a growth medium supported by a plastic layer, with a gas-permeable layer below it separating the medium from an external air space (Compl. p. 11). Sarepta’s alleged use of the HYPERStack device is linked to its efforts to develop and commercialize its gene therapy products, including activities such as establishing a "manufacturing partnership" and entering a significant out-of-U.S. license agreement (Compl. ¶¶ 31-33).
IV. Analysis of Infringement Allegations
’192 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| adding medium and animal cells into a static cell culture device | Medium and cells are added to the HYPERStack, which is alleged to be a static cell culture device. | ¶35 | col. 1:17-19 |
| that is not compartmentalized by a semi-permeable membrane | The complaint alleges the HYPERStack does not have a semi-permeable membrane. | ¶35 | col. 9:14-16 |
| at least a portion of said cell culture device is comprised at least in part of a nonporous gas permeable material | The HYPERStack device is alleged to function via a gas permeable material that allows for gas exchange. | ¶35 | col. 22:5-9 |
| ambient gas is in contact with at least a portion of said gas permeable material | Gas exchange allegedly occurs via "air spaces ... beneath each culture chamber which is open to the atmosphere." | ¶35 | col. 22:5-9 |
| placing said cell culture device in a cell culture location that includes ambient gas... | The HYPERStack is allegedly moved to and used in an incubator containing ambient gas suitable for cell culture. A photograph in the complaint depicts a HYPERStack device being placed into an incubator (Compl. p. 11). | ¶35 | col. 2:19-22 |
| wherein said cell culture device is oriented in a position such that at least a portion of said cells reside upon at least a portion of said gas permeable material | The complaint alleges the HYPERStack is placed in an incubator such that cells reside on the gas permeable material. A diagram shows cells residing above the gas permeable layer (Compl. p. 11). | ¶35 | col. 22:9-12 |
| the uppermost location of said medium is elevated beyond 2.0 cm from the lowermost location of said medium | The complaint alleges the uppermost location of the medium is elevated more than 2.0 cm, stating this can be "appreciated" from a picture. | ¶35 | col. 17:7-9 |
| and said device is in a state of static cell culture | The complaint alleges the HYPERStack is cultured in a static state. | ¶35 | col. 2:48-51 |
’443 Patent Infringement Allegations
| Claim Element (from Independent Claim 26) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A method of culturing cells in a cell culture device comprised at least in part of a gas permeable material and including at least one access port and including at least two scaffolds... | The HYPERStack is alleged to be a device made with gas permeable material, having at least one access port and at least two scaffolds (the stacked layers). | ¶36 | col. 29:34-39 |
| a) adding cells and a volume of liquid medium into said cell culture device | The complaint alleges that cells and media are added into the HYPERStack. | ¶36 | col. 45:7-8 |
| b) orienting said cell culture device into an inoculation position such that said scaffolds reside at different elevations within said cell culture device | The complaint alleges the device is oriented such that the scaffolds reside one above the other at different elevations, as shown in a diagram (Compl. p. 12). | ¶36 | col. 45:9-12 |
| c) allowing cells to settle upon said scaffolds | The complaint alleges that cells settle upon the scaffolds. | ¶36 | col. 45:13 |
| d) adding enough liquid medium to prevent a unique gas-liquid interface from forming directly above at least one scaffold... | The complaint alleges the user adds enough liquid medium to the HYPERStack to prevent a unique gas-liquid interface by eliminating the need for internal headspace. | ¶36 | col. 45:14-21 |
| e) placing the cell culture device in a cell culture location that includes ambient gas... | The complaint alleges the HYPERStack is placed in an incubator where ambient gas makes contact with the device's gas permeable material via "air spaces." A photograph depicts this action (Compl. p. 13). | ¶36 | col. 45:22-26 |
| f) not perfusing said liquid medium when said device is in said cell culture location | The complaint alleges the liquid medium in the HYPERStack is not perfused when the device is in the incubator. | ¶36 | col. 45:27-29 |
Identified Points of Contention
- Scope Questions: A central legal dispute will be whether Sarepta's activities fall under the 35 U.S.C. § 271(e)(1) Safe Harbor for activities "solely for uses reasonably related to the development and submission of information under a Federal law which regulates" drugs (Compl. ¶¶ 34, 42). The complaint alleges commercialization activities that may place Sarepta's use of the process outside this exemption (Compl. ¶¶ 31-33).
- Technical Questions: For the ’192 Patent, a key factual question is whether the liquid medium in the accused process is actually "elevated beyond 2.0 cm." The complaint asserts this can be "appreciated" from a photograph, which raises the evidentiary question of how this critical dimension will be proven (Compl. p. 11). For the ’443 Patent, a question may arise as to whether the stacked plastic trays of the HYPERStack device meet the definition of "scaffolds" as that term is used in the patent.
V. Key Claim Terms for Construction
The Term: "static cell culture" (’192 Patent, Claim 1)
Context and Importance: This term is critical because the claim is limited to a method performed in a "static" state. Defendant may argue that its large-scale, industrial manufacturing process is not "static" in the sense contemplated by the patent, which focuses its background discussion on displacing traditional laboratory flasks. The construction of this term could determine whether the claim reads on the accused industrial-scale process.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification of the parent ’443 Patent, incorporated by reference, defines "static devices" as those that "do not require ancillary equipment to mix or perfuse the cell culture medium" (’443 Patent, col. 2:48-51). This could support a construction covering any non-perfused, non-mixed system, regardless of its scale or automation.
- Evidence for a Narrower Interpretation: The background section contrasts the invention with small-scale laboratory equipment like "the traditional petri dish, multiple well tissue culture plate, [and] tissue culture flask" (’443 Patent, col. 2:54-56). This context may support an argument that "static" implies a smaller, simpler laboratory-bench scale of operation.
The Term: "scaffolds" (’443 Patent, Claim 26)
Context and Importance: The infringement theory for the ’443 Patent hinges on the stacked layers of the HYPERStack device constituting "scaffolds." Practitioners may focus on this term because if "scaffolds" is construed to require a particular structure (e.g., a porous, three-dimensional matrix common in tissue engineering) not present in the HYPERStack's solid plastic trays, the infringement allegation could fail.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification provides a potentially broad definition, stating that scaffolds "can be any geometric shape that allows cells to attach" and can be made of polystyrene, the same material as traditional flasks (’443 Patent, col. 30:52-54; col. 35:43-45). The figures depict scaffolds as simple flat or corrugated sheets (e.g., ’443 Patent, Figs. 10A, 12A).
- Evidence for a Narrower Interpretation: A defendant could argue that in the context of cell culture, one of ordinary skill would understand "scaffold" to mean something more than a simple surface, potentially pointing to other uses of the term in the field to suggest a more limited, structural meaning.
VI. Other Allegations
- Indirect Infringement: The complaint does not provide sufficient detail for analysis of indirect infringement. The prayer for relief seeks to enjoin inducing and contributory infringement, but the factual allegations and specific counts only plead direct infringement under 35 U.S.C. § 271(g) (Compl. ¶¶ 24, 39-41, p. 15).
- Willful Infringement: The complaint does not contain an explicit allegation of willful infringement.
VII. Analyst’s Conclusion: Key Questions for the Case
- A central legal issue will be the application of the 35 U.S.C. § 271(e)(1) Safe Harbor: the court will need to determine whether the defendant's alleged manufacturing and commercialization-related activities, such as partnerships and licensing deals, remove its use of the patented process from the scope of the statutory exemption for activities solely related to FDA data submission.
- A key evidentiary question will be one of dimensional proof: can the plaintiff provide sufficient evidence to demonstrate that the accused process meets the quantitative limitation of Claim 1 of the ’192 Patent, specifically that the liquid medium is "elevated beyond 2.0 cm," a point the complaint supports only by reference to visual "appreciation" of a photograph?
- A dispositive claim construction issue may be one of definitional scope: does the term "scaffolds," as used in the ’443 Patent, broadly cover the stacked, solid polystyrene trays of the accused HYPERStack device, or does intrinsic evidence and the understanding of a person of ordinary skill in the art support a narrower definition that the accused device does not meet?