On August 26, 2021, the Federal Circuit revisited the written description requirement in determining patent validity in Juno Therapeutics v. Kite Pharma. In this case, the Federal Circuit’s decision addressed Juno’s patent written description between Juno Therapeutics and Kite Pharma over Kite’s CAR-T anticancer therapy, Yescarta®. Yescarta® is a $373,000 per treatment regimen. Juno does not market a competing product.
In general, CAR-T anticancer therapy works by modifying a patent’s T cells to stimulate a patient’s immune response against tumor cells. CAR-T cells involve a Car-T receptor comprised of a zeta chain portion with (a) intracellular domain of CD3 ζ chain (a signaling domain that activates to trigger an initial immune response when T Cells bind to antigens) (b) a co-stimulatory signaling region, (The stimulation of this region causes T cells to multiply), and (c) specific binding element that binding to an expressed antigen by a target cell (e.g. tumor). A nucleic acid encoding CAR is introduced into a patients’ T cells after isolation from the patients. Then, these T Cells are reintroduced and bind to patients’ tumor cells. This process allowing for the cascade of these tumor-specific T cells and causing tumor cell deaths.
The ‘190 patent claims three specific elements of the CAR-T therapy: scFv, CD28, and CD3ζ. Claim 1 of the ‘190 patent is below:
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.
Juno initially sued Kite for infringing claims 3, 5, 9, and 11 of its 7,446,190 (the ‘190) Patent. Kite countered arguing that Juno’s ‘190 patent is invalid for failure to satisfy the written description requirement of 35 U.S.C. Section 112. In the District Court, the jury determined that Kite did not show clear and convincing evidence that the asserted claims of the '190 Patent were invalid for failure to meet the written description requirement under 35 U.S.C. § 112(a). In doing so, the District Court awarded Juno a $1.2B judgment which included over $778 million on the jury verdict to account for Kite's infringing sales of Yescarta® not accounted for by the time of trial, enhanced damages of over $389 million for Kite's willful infringement, and an ongoing royalty of 27.6% on Yescarta® revenues through patent expiration. However, the Federal Circuit reversed the lower court’s decision and vacated a $1.2B judgment to Juno Therapeutics.
The main issue, in this case, was a single-chain antibody variable fragment or scFv. This binding element is forged by linking antigen-binding portions of the heavy and light chain of an antibody’s variable region to form the binding element. The Federal Circuit used this fact to reverse the lower court's decision as each variable region contains a unique amino acid sequence that dictates how scFVs will bind to the target.
The ‘190 Patent disclosed only two scFvs, one ScFv that binds to CD19 protein and the other that binds to PSMA. However, the patent failed to describe and disclose the amino acid sequence of either of these scFvs. The Federal Circuit cited Ariad Pharms. V. Eli Lilly (Eli Lilly) to determine that the ‘190 patent failed to meet the written description requirement. A written description of a biological or chemical invention would require “a precise definition, such as by structure, formula, [or] chemical name," to distinguish itself from other materials.
The Federal Circuit further sided with Kite’s argument that the ‘190 patent did not disclose the representative species or common structural features of the scFv genus to identify which scFvs would function as claimed in the patent. There was no specification of which scFvs bind to given specific targets, so that the written description does not meet the written description for functional binding limitation and that scFvs’ binding ability depends on several factors.
The Court also assessed the failure to satisfy the written description requirement for dependent claims 3 and 9. The Court interpreted claims 3 and 9 to mean “any scFvs for binding any target.” The Court gave an opinion that ‘190 patent “fail[ed] to provide a representative sample of species within, or defining characteristics for, that expansive genus” Thereby, claims 3 and 9 failed the written description requirement of Eli Lilly.
The Federal Circuit also rejected Juno’s expert testimony to counter Kite’s invalidity contentions by stating that Juno’s written description requirement did not “lead a person of ordinary skill in the art to understand that the inventors possessed the entire scope of the claimed invention.” Furthermore, the Court formed an opinion that for Juno to claim that general knowledge of scFvs was sufficient, they needed to convey they possessed “the claimed invention, encompassing all scFvs, known and unknown, as part of the claimed CAR that binds to a selected target.” This would be an impossible standard for Juno to have met.
The Federal Circuit also looked at the alternative Eli Lilly test to satisfy the written description requirement. There too, the Federal Circuit found the ‘190 specification lacking. The Court acknowledged that scFvs have structural commonalities and that the differences in amino acid sequences determine the binding specificities to a variety of antigens. However, the ‘190 patent failed to disclose a way to distinguish binding-capable scFvs from binding-incapable scFvs of specified targets.
The opinion also looked at asserted claims 5 and 11, regarding the limitations of scFvs binding to CD19. The Court agreed with Kite stating that this limitation does not satisfy the written description requirement because there are only a few scFvs that bind to CD19 known in the prior art. This factor is important because there could potentially be millions or billions of possible sequences of scFvs.
The major lesson from this decision is that the Court narrowed the scope of antibody patent claims. Now, claims regarding antibodies will have to resemble closely with a company’s antibody products. With antibody claims, companies will need to disclose some of the structures of the antibody product rather than submitting broad claims using languages such as “binding elements,” “costimulatory regions,” etc. Inventors will only get patent protection for the disclosed items. This case will allow others to make derivative products to make more competing species of antibodies. One positive side of this case is that there will be an increase in the number of potential antibody-related inventions. However, with the lack of protection, the inventors might not even innovate to make antibody-related products at all.
However, there is a way to build a patent portfolio that can withstand some of the recent written description decisions, including Sanofi. Companies will need to build a patent portfolio with many layers to create a “patent thicket.” The most important features of a successful patent thicket are 1) the number of patents; 2) the diversity of the portfolio; 3) the timing of its patent application. There is a trade-off: this strategy is very expensive. However, if a patent is worth protecting, the patent portfolio method is highly recommended.
For antibody patents, each patent should claim the subject matter using different formats yielding differences in scope so that some of the patents can survive the potential post-grant challenge. This can be done by including a set of narrower claims that include parts of antibody sequence or other features of the antibody. Furthermore, functional elements could be coupled with structural elements in the same claim, creating hybrid claims. It would also greatly help if the company could staggeringly file these patents to include a range of different patent claims that act to extend the patent term.
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