On behalf of patentee Sloan Kettering Institute for Cancer Research and exclusive licensee Juno Therapeutics (a subsidiary of Celgene Corporation, a Bristol Myers Squibb company), Jones Day and co-counsel prevailed in a jury trial and on post-trial motions, resulting in a final judgment of over $1.1 billion plus ongoing royalties for Kite Pharma, Inc.’s willful infringement of Sloan Kettering’s CAR-T cell patent, U.S. Patent 7,446,190. Sloan Kettering and Juno proved that Kite’s making and selling of YESCARTA®, the first CAR-T cell therapy approved by FDA for treating relapsed or refractory large B-cell lymphoma, infringed the ’190 patent and that Kite’s infringement was willful, and defeated Kite’s claims of invalidity as to the asserted patent claims and a post-issuance correction to the patent. Kite has filed an appeal in the case.
Gilead acquired Kite in 2017 for $12 billion. Celgene acquired Juno in 2018 for $9 billion.
Patent Strategy is a Necessity, not a Luxury, for CAR-T Companies
Thesubstantial judgment amount in the Juno case is a reflection of the value of CAR-T patents. It reinforces the message that CAR-T companies must be proactive about developing a strategy to build a robust patent portfolio and implement the strategy with a strong sense of urgency.
Detailed patent landscape analysis is critically important for identifying valuable IP portfolios from academia or start-ups for acquisition. Patent prosecution and portfolio strategy requires experienced and high quality counsel not only in anticipation of future invalidity challenges, but also for due diligence in financing and partnering.
A thorough freedom-to-operate analysis should be performed early in and often during the development of CAR-T cell therapy to identify and preempt infringement risks.
A global strategy for CAR-T patent portfolio development that takes divergent patentability standards in different jurisdictions into account is also of critical importance. A robust global patent portfolio provides a solid foundation to support cross-border partnerships and collaborations.
The Devil is in the Details for a Successful CAR-T Patent Strategy
The complexity of CAR-T cell therapy poses unique challenges for IP protection. A combination of technical know-how and sophisticated IP strategy is necessary for tailoring patent strategy to a company’s particular CAR-T platform. Patentable inventions may be in the categories of compositions, manufacturing methods, methods of treatment, and medical uses, each with unique features for the CAR-T technology.
Applicants can pursue composition of matter claims directed to CAR-T cells and their components, for example, CAR proteins, populations of expanded CAR-T cells, CAR-encoding polynucleotides, and vector constructs. Patent strategies can rely on new targets, combinations of various binding specificities, novel extracellular domain structures, and modifications for optimization of other engineered functional domains of CAR proteins, including transmembrane domains and intracellular domains such as the costimulatory domain. As an example, the patent in the above-mentioned Juno litigation contains composition claims directed to a CAR-encoding polynucleotide.
Composition of matter claims covering CAR-T cells rather than the CAR component itself may face unique challenges in terms of enforcement. CAR-T cells, especially autologous CAR-T cells, are individually produced for each patient and infused into the patient a single time soon after being produced, rendering testing of alleged infringing cells to establish infringement of each claim element potentially difficult or infeasible. Therefore, claim drafting strategies should be thoughtfully designed to encompass the inventive gist in a manner that takes into account the unique attributes of this therapy.
Another category of claims for CAR-T inventions are directed to manufacturing methods. While autologous CAR-T cell therapy has enjoyed great clinical triumphs with certain blood cancers such as B-cell malignancies, including KYMRIAH® and YESCARTA®, the requirement of a bespoke manufacturing process for each individual patient makes scaling up impossible and quality control difficult. Allogeneic CAR-T cells from healthy donors represent a burgeoning area of interest in CAR-T cell therapy. Off-the-shelf allogenic CAR-T cell therapy provides the advantages of immediate availability, industrialized manufacturing and potential standardization. In addition to composition features of allogeneic CAR-T cells, inventions directed to allogeneic CAR-T platforms may be directed to the manufacturing process and include features such as, for example, the use of TALEN, CRISPR or other gene editing technologies.
Notably, enforcement of manufacturing process claims has its challenges. Manufacturing claims generally protect the process of making CAR-T cells, but not the CAR-T cells themselves. Moreover, CAR-T manufacturing processes and corresponding patent claims involve multiple steps, which are often performed by multiple entities, and thus present various challenges for a patentee seeking to prove infringement. In addition, a competitor may attempt to evade infringement liabilities by making slight adjustments to the process of manufacturing the CAR-T cells. Consequently, a patent applicant should consider all aspects of the manufacturing method, analyze their constituent steps and determine the optimal strategy to draft claims directed to those key aspects of the process sufficient to confer patentability and most difficult for competitors to designing around. Moreover, the use of trade secrets to protect manufacturing technology or other know-how can provide a critical advantage. Employee mobility and the need to collaborate also heightens the need for appropriate trade secret training and procedures.
Method of treatment and medical use claims are also components of any comprehensive patent portfolio protecting CAR-T cell therapy. Yet, examination standards for such claims vary significantly from country to country and should not be solely relied upon for protecting a CART platform. In addition, applicants need patent prosecution support from a team familiar with patentability standards for such claims in the various jurisdictions where patent protection is sought.
Finally, an effective patent life cycle management strategy, including securing patent term extensions in various jurisdictions, requires experience and skill best found in counsel with product approval experience.
As CAR-T demonstrates the healing power of engineered cells, companies paying attention to patent strategy will enjoy the fruits of their innovation.
The views and opinions set forth herein are the personal views or opinions of the author; they do not necessarily reflect views or opinions of the law firm with which [he/she] is associated.