In August 2017, the U.S. Food and Drug Administration (FDA) approved Novartis’ Kymriah (tisagenlecleucel) for the treatment of certain pediatric and young adult patients with a specific form of leukemia. Kymriah is the first gene therapy to be approved by the FDA and represents a milestone for the treatment of cancer using Chimeric Antigen Receptor (CAR) T cells.
CAR-T cells hold a great promise for treating cancer and one estimate suggests that the sales of engineered T cells will reach $10 billion annually by 2021.1 Not surprisingly, a number of other companies are working on cell-based immunotherapies and it is likely that the use of CAR-T cells will expand beyond haematological malignancies to the treatment of other cancers and solid tumours.
There is also a need for innovations regarding the manufacture and quality control of cell-based therapies, including methods for defining specific cell types and improving the purity of CAR-T cell products and dosing. Furthermore, advances in abrogating toxicities observed with the use of CAR-T cells (including cytokine release syndrome) may prove to be very valuable. Significant opportunities exist, however, the landscape is competitive. Obtaining effective patent protection is critical to help position innovators and companies working in this field for commercial success.
Patentability of cell-based therapies
Patent rights are governed by the laws of each individual country or jurisdiction where a patent application is filed. While the specific requirements for obtaining a patent vary from country to country, most patent systems require that the invention defined by the claims be considered patentable subject matter, represent a novel and non-obvious (inventive) advance over the prior art, and have a utility that is supported by the application. Recently, whether certain inventions qualify as patentable subject-matter has been a concern particularly before the U.S. Patent Office. In general, cells that are the product of genetic engineering such as CAR-T cells should qualify as they have “markedly different characteristics” from any naturally occurring counterpart. Furthermore, in the U.S., methods of medical treatment, as well as methods for the production of genetically engineered cells, should also qualify as patentable subject matter.
Inventions related to genetically engineered cells should also qualify as patentable subject matter in other jurisdictions. Although method-of-treatment claims are generally not allowed outside of the U.S., corresponding use claims should be available. For example, a number of patents have been granted in Europe and Canada with claims directed to CAR-T cells, their use for treating disease, as well as methods for producing genetically engineered T cell receptors and T cells.2 A claimed invention must be novel and non-obvious over the prior art.
The prior art includes public disclosures of information (such as research papers or published patent applications) made before a patent application is filed. While even minor differences are normally sufficient to establish novelty, proving that an invention is nonobvious can be challenging especially in a rapidly developing field such as cell-based immunotherapy. Carefully describing features or elements that distinguish the invention or that are unexpected or surprising can often help establish that a claimed invention is non-obvious.
Clinical data demonstrating the utility of an invention in humans is rarely available at the time of filing a patent application, however other types of data can normally be used for support. For example, it may be possible to support claims to the use of genetically engineered cells in humans based solely on in vitro and/or animal data. Talking to a patent agent or lawyer at the outset of a research project can help clarify what data may be sufficient to support the utility of an invention and file a patent application.
Enforcement and licensing
The amount of research and development required to launch a new therapy such as CAR-T cells is enormous and obtaining patent rights to protect commercial uses of the technology is paramount. Prior to launching Kymriah, Novartis reached an agreement with Juno Therapeutics to settle a long-running patent dispute, allowing each to advance with their respective CAR-T cell therapies. According to the terms of the settlement, Novartis and its partner, the University of Pennsylvania, will pay $12.25 million, plus future milestone payments and royalties on CAR-T cell products to Juno and St. Jude Children’s Research Hospital. Kite Pharma is another company engaged in the development of CAR-T cell therapies who amassed a significant patent portfolio.3
In August 2015, Kite filed for an inter partes review of U.S. Patent No. 7,446,190 (the ’190 Patent) of which Juno is the exclusive licensee, alleging that all of its claims were obvious. The U.S. Patent Office upheld the validity of the claims in the ‘190 Patent4 and Juno, in turn, filed a patent infringement lawsuit against Kite, seeking a declaration that one of Kite’s lead therapies infringes the ‘190 Patent. On June 13, 2017, the District Court of Delaware granted Kite’s motion to dismiss the suit but it is unlikely that this will be the end of legal proceedings regarding patent rights between these competitors. In late August 2017, Gilead Sciences announced that it was acquiring Kite for $11.9 billion. In one swoop, Gilead acquired all of Kite’s patent assets and has become a major player in the development and commercialization of CAR-T cell therapies.
Herman Cheung is an associate with Bereskin & Parr LLP and is a member of the Life Sciences practice group. Laurence MacPhie is a lawyer and partner with Bereskin & Parr LLP
1.Kitamura, M. 2015. GE Sees Cell Therapy Industry’s Sales at $10 Billion by 2021. Bloomberg. October 21, 2015. https://www.bloomberg.com/news/articles/2015-10-21/ge-sees-cell-therapyindustry-s-sales-at-10-billion-by-2021
2. See for example Canadian Patent Nos. 2,566,363 and 2,674,445 as well as European Patent No. EP2016102.
3. Kite Pharma states that the company has intellectual property portfolio that encompasses more than 150 patent assets, many of which relates to
T-cell therapies; see Kite Pharma, December 19, 2016, Press Release [Kite]: http://ir.kitepharma.com/releasedetail. cfm?ReleaseID=1004781.
4. Kite Pharma, Inc. vs. Sloan Kettering Institute for Cancer Research, 2016, United States Patent Trial and Appeals Board, Case IPR2015-01719, Patent 7,446,190 B2. Kite Pharma has appealed this decision.
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