IP Law Daily Claims for treating cancer with ‘natural killer’ cells were invalid as obvious
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Wednesday, May 3, 2017

Claims for treating cancer with ‘natural killer’ cells were invalid as obvious

A patent application’s claims for the use of a specific type of immune cells to treat cancer were invalid as obvious, the U.S. Court of Appeals for the Federal Circuit has held in a split decision. The court affirmed a district court’s decision that the USPTO properly rejected the claims. A person of ordinary skill would have been motivated to combine prior art references to arrive at the treatment method of the rejected application, which involved the use of certain "natural killer" immune cells to destroy cancer cells. The district court’s use of an incorrect construction of the term "cancer" was harmless error. A dissenting judge argued that the owner of the application had presented evidence raising a genuine factual issue as to whether a skilled artisan would reasonably expect to succeed in combining one prior art reference’s in vitro experimental results with another reference’s in vivo therapeutic methods (NantKwest, Inc. v. Lee, May 3, 2017, Dyk, T.).

Patent application at issue. U.S. Patent Application No. 10/008,955 ("the ’955 patent application") was held by NantKwest, Inc., by assignment from the patent applicant, Hans Klingemann. The ’955 patent application concerned the use of a particular cell line of natural killer (NK) cells, called NK-92, to destroy (or "lyse") cancer cells. One of the claims at issue also added a treatment method consisting of administering a cytokine that promoted the growth of NK-92 cells. NK cells comprise a type of immune cells that have different cell surface proteins and respond to target cell receptions differently from another type of immune cells, T cells, which attack specific foreign antigens that they have been trained to recognize. NK cells are part of the innate immune response and rapidly attack anything they sense as foreign to the body. The more discriminate T cells are part of the adaptive immune response. At the time the ’955 patent application was filed—in 1997—NK cells and T cells were the only two types of immune cells known to recognize and lyse tumor cells in vivo in mammals.

Prior art. The USPTO relied on two prior art references in rejecting the claims. First, U.S. Patent No. 5,272,082, by Santoli et al. ("Santoli"), taught that a specific cell line of T cells, TALL-104, can be used in vivo to treat cancer. Second, Gong, Maki, and Klingemann (the ’955 patent applicant) published a study ("Gong") that taught that a specific NK cell line, NK-92, can lyse cancer cells in vitro with high efficacy. The patent examiner rejected the three claims at issue, finding that "it would have been prima facie obvious to a person of ordinary skill in the art … in April 1997 to combine the teachings of Santoli and Gong to arrive at the claimed method because Gong … teaches use of NK-92 cells to lyse tumor cells, while Santoli … teaches in vivo use of cytotoxic cell lines."

Review proceedings. The applicant appealed to the Board of Patent Appeals and Interferences. The Board affirmed the examiner’s rejection on the ground that a person of ordinary skill in the art would have been motivated to replace the TALL-104 cells in Santoli’s method with NK-92 cells, based on Gong’s disclosure that NK-92 cells spontaneously kill leukemia and lymphoma cancer cells with high efficiency. NantKwest then filed a complaint in district court under 35 U.S.C. §145, seeking judgment that the three claims at issue were nonobvious. The USPTO moved for summary judgment, and the district court granted the USPTO’s motion. NantKwest appealed to the Federal Circuit.

Claim construction. NantKwest argued that the grant of summary judgment should be reversed because the district court used an incorrect construction of the claim term "cancer." Initially, the district court construed "cancer" to mean a "plurality or multiple cancer cells," but in addressing the question of the reasonable expectation of success (an element of the obviousness analysis), the court apparently considered "cancer" as meaning "one or more cancer cells." The Federal Circuit agreed that the latter construction was incorrect, but it held that the erroneous claim construction created no basis for reversal. In reviewing the district court’s decision de novo, the appellate court applied the correct construction—rending the lower court’s error harmless—and under that construction, the result was the same. There was no assertion that the relevant prior art references taught methods that only lysed one cancer cell or otherwise lysed insufficient numbers of cells for treating cancer, the Federal Circuit explained.

Obviousness. The Federal Circuit agreed with the district court that there was no material dispute that the combination of Santoli and Gong produced the invention and that persons of ordinary skill in the art would have been motivated to combine Santoli and Gong. Santoli showed that T cells from a cell line, not belonging to a patient, could be administered to produce therapeutic effects. Santoli taught that the TALL-104 cell line could be used in this fashion for lysing cancer cells. Gong taught that the NK-92 cell line was effective and highly efficient for lysing the same cancer cells as the TALL-104 cell line. Additionally, prior art publications by Klingemann himself indicated that there was a motivation to seek clinical application for the NK-92 cell line. The ’955 patent application itself referred to Gong to describe the superior qualities of the NK-92 cell line. NantKwest’s expert conceded that in 1997, skilled artisans knew that NK cells and T cells were the only two types of immune cells known to have antitumor efficacy.

The Federal Circuit rejected NantKwest’s argument that certain prior art references submitted for the Section 145 proceeding raised factual questions because they involved the use of NK-92 cells in vitro rather than in vivo. There was no general rule that a skilled artisan could not reasonably extrapolate in vivo success from in vitro results, and in this case, there was overwhelming specific evidence that a skilled artisan could reasonably extrapolate from the in vitro data with respect to TALL-104 and NK-92 that would reasonably teach their successful substitution in vivo.

Secondary considerations. NantKwest contended that it had presented secondary considerations of nonobviousness that should have been sufficient to preclude summary judgment. This evidence included a news report about a $48 million investment in NantKwest. However, the Federal Circuit said, there was no direct nexus between that investment and the merits of the claimed invention that would indicate commercial success. Rather, the evidence showed that the stock purchase was made for corporate control purposes.

Dissenting opinion. Circuit Judge Kara Farnandez Stoll, writing in dissent, argued that NantKwest submitted evidence and expert testimony showing that an ordinarily skilled artisan at the time of the invention would not have had a reasonable expectation of success in combining Santoli’s in vivo results for TALL-104 cells with Gong’s in vitro experiments for NK-92 cells. In Judge Stoll’s view, this evidence created a genuine dispute of material fact that barred the grant of summary judgment.

The case is No. 2015-2095.

Attorneys: Alan J. Heinrich (Irell & Manella LLP) for NantKwest, Inc. Mary L. Kelly, U.S. Patent and Trademark Office, for Michelle K. Lee.

Companies: NantKwest, Inc.

MainStory: TopStory Patent FedCirNews

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