Patenting Personalized Medicine: Lessons from CAR T Cell Therapy in the U.S.

Patenting Personalized Medicine: Lessons from CAR T Cell Therapy in the U.S.

Written by: Dr. Anglea Keuling

Personalized medicine, also known as precision medicine, involves tailoring medical treatment to each individual patient based on genetic markers or other physiological characteristics. Such therapies can increase the patient’s response to treatment and reduce potential side effects. However, compared to conventional pharmaceuticals that typically consist of a single active compound, the high variability of personalized medicine can pose challenges for patenting a new therapy.

These challenges were recently illustrated in Juno Therapeutics vs. Kite Pharma Inc., No. 20-1758 (Fed. Cir. 2021), in which the United States Court of Appeals for the Federal Circuit reversed a massive $1.1 billion jury verdict for infringement of a patent relating to CAR T cell therapy.

Background

Chimeric antigen receptor (CAR) T cell therapy is a personalized treatment for cancer that involves isolating a patient’s T cells and reprogramming those T cells to produce a specific, targeted receptor (a CAR) on each T cell’s surface. The patient is infused with the reprogrammed T cells to specifically attack the cancer cells in the patient’s body.

The patent at issue in this case was U.S. Patent No. 7,446,190 (the ‘190 patent) held by Sloan Kettering Institute for Cancer Research and exclusively licensed to Juno Therapeutics (“Juno”). The ‘190 patent relates to a nucleic acid polymer encoding a three-part CAR for a T cell. Claim 1 of the ‘190 patent reads as follows:

1. A nucleic acid polymer encoding a chimeric T cell receptor, said chimeric T cell receptor comprising

(a) a zeta chain portion comprising the intracellular domain of human CD3 ζ chain,

(b) a costimulatory signaling region, and

(c) a binding element that specifically interacts with a selected target, wherein the costimulatory signaling region comprises the amino acid sequence encoded by SEQ ID NO:6.

The binding element is the key portion of the CAR that determines what target molecule the reprogrammed T cell can recognize and bind to. The main type of binding element disclosed in the ‘190 patent is a single-chain antibody variable fragment (scFv).

Juno sued Kite Pharma Inc. (“Kite”), alleging infringement of various claims of the ‘190 patent by Kite’s YESCARTA® therapy, which uses a three-part CAR containing an scFv that targets certain antigens of B-cell lymphoma and leukemia cells. At trial, a jury reached a verdict in Juno’s favor and Juno obtained a $1.1 billion judgement. Kite then appealed the decision to the Court of Appeals for the Federal Circuit.

The Decision

The main issue in the appeal was whether the claims of the ‘190 patent were invalid for lack of sufficient support by the written description.

Claim 1 of the ‘190 patent recites a binding element “that specifically interacts with a selected target”. The claims therefore cover a genus encompassing an enormous number (millions of billions) of scFv candidates that could potentially bind to all possible targets. The Court of Appeals noted that, generally, a genus can be sufficiently disclosed by either a representative number of species (i.e. examples) falling within the scope of the genus or by structural features that would allow a skilled person to recognize members of that genus.

The ‘190 patent’s written description contains few details about which scFvs can bind to which targets. The ‘190 patent only includes two examples of scFvs: one that binds to a specific antigen on B-cell lymphoma cells and one that binds to a specific antigen on prostate cancer cells. The amino acid sequences of the two scFvs were not disclosed.

The Court found that the two exemplary scFVs in the ‘190 patent (in addition to a handful of known scFvs in the prior art) were not sufficiently representative of the vast number of possible scFvs for an indeterminate number of targets. In addition, the ‘190 patent does not provide any meaningful guidance about selecting an appropriate scFv as it “does not disclose any amino acid sequences or structures to distinguish scFvs that bind to that selected targets from those that do not, and the modifications of the sequence can change the binding ability”.

The Court of Appeals therefore held that “the ‘190 patent’s written description fails to provide a representative sample of species within, or defining characteristics for, that expansive genus”. For these reasons, the Court reversed the jury’s verdict on the issue of written description.

Conclusions

The patent system is based on a quid pro quo in which an inventor receives a limited monopoly for an invention in exchange for disclosing that invention to the public. The sufficiency of the written description of a patent is therefore critical to the patent’s validity.

For personalized medicines that may encompass a vast number of possible treatment variations, meeting the written description requirement can be challenging. The CAR T cell therapy case illustrates the importance of including as many working examples as possible and/or details regarding the specific structure or sequence of the molecule or compound that forms the basis for the treatment.

 

If you are interested in potentially patenting a personalized medicine invention, our intellectual property team is happy to help you navigate this space.