November 29, 2020

Volume X, Number 334

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Dana-Farber v. Ono – Co-Inventorship Rules

The pun is intentional, since in Dana-Farber Cancer Inst. v. Ono Pharm. Co., Ltd, Appeal No. 2019-2050 (Fed. Cir., July 14, 2020), a Fed. Cir. Panel of Judges Lourie, Newman and Stoll, Lourie writing, affirmed a district court ruling that two collaborators should have been named as co-inventors with the four named inventors on U.S. patent no. 7,595,048 and five progeny patents. This mercifully compact opinion provides a very good summary of the law of co-inventorship, particularly in a complex area of biotechnology with a number of potential collaborators who interacted at different times to provide different contributions to the conception of claimed subject matter. Claim 3 of the ‘048 patent is deceptively simple:

“ A method for enhancing cytotoxic T Cell activity toward PD-L1 or PD-L 2 over-expressing cancer cells, which comprises administering a pharmaceutically effective  amount of a completely human anti-PD-1 antibody to a subject with cancer in which PD-L1 or PD-L2 is overexpressed, wherein the effective dose …is administered parenterally and post-operatively.”

After a rather dense attempt to summarize the workings of the immune system, Lourie summarizes the invention:

“The discovery behind the present patents was the existence of an inhibitory receptor on T Cells, PD-1, and that, when PD-1 binds to one of its ligands [expressed by normal or tumor cells], either PD-L1 or PD-L2, the T cell is inhibited and does not attack the cell expressing the ligand. Expression of the PD-1 ligands in healthy cells generally shield them from attack, but some tumor cells can also express the ligands, allowing them to circumvent an immune response. The patents in this case capitalize on the discovery of the PD-1 receptor-ligand interaction. Each claim recites uses of antibodies that target either the PD-1 receptor or its PD-L1 ligand, blocking the receptor-ligand interaction. By blocking the interaction, the use of the inventions in effect stimulates the immune response against tumor cells that would otherwise have been hidden by [the tumor cells] expression of the PD-L1/L2 ligands.”

Dana-Farber sued to add two researchers, Drs. Freeman and Woods to the patents naming,, inter alia, Dr. Tasuko Honjo, who eventually won the Nobel Prize for his work in this area, discovered the PD-1 receptor and determined, via a knock-out mouse model, that PD-1 was involved in immune system inhibition. A co-worker found that a variety of tumor cell lines could bind PD-1. This early work was published in August 1999.

The collaboration began when, in 1998,  Ono connected him to Dr. Wood, a researcher at Genetics Institute, who would collaborate with Dr. Honjo, with the aim of identifying the PD-1 receptor. In July 1998, Dr. Freeman, a researcher at Dana-Farber, was studying the T cell B-7 ligands, that bind to a different receptor on T cells. He discovered a close amino acid sequence to the B-7 binding site, which Drs. Wood and Freeman found would bind PD-1. It was labelled PD-L1. Dr. Wood disclosed that PD-1 antibodies were found to inhibit the PD-1/PD-L1 interaction. Dr. Honjo believed that PD-1 would inhibit the immune response. Dr. Freeman discovered a second amino acid sequence, PD-L2, that had similar properties. “By May 2000 [the trio] were discussing their development of anti -PD-L1 antibodies and the possible use of those antibodies in treating cancer.”

Ono  argued that conception of the invention by the Honjo group occurred in October 2000 when Honjo and Minato, using mouse data obtained by Dr. Iwai, “discussed the possible use of PD-1 for treating cancer.”Dr. Honjo learned that Wood and Freeman had filed a patent application that did not name him as a co-inventor, and his group filed a patent application in 2002, not naming Freeman or Wood as co-inventors. By April 2001 the collaboration was over. Dana-Farber filed a suit to amend the Honjo patent to add Drs. Wood and Freeman as cc-inventors. Since such an amendment would give Dana-Farber an interest in the Honjo group’s application, assignee Ono refused to add Wood and Freeman as co-inventors.

Ono argued that the contributions by Wood and Freeman were too far removed from the patents’ claims, and that their contributions had been published and so were in the prior art before the alleged conception.. Ono also argued that experiments conducted independently by the Honjo group were what led to the conception of the invention. The Honjo group’s work was published in Oct. 2000. Ono argued that the previous Wood/Freeman work was speculative since it was conducted in vitro.

35 USC provides the standard for joint inventorship. To summarize, inventors may apply for a patent even though they did not physically work together or at the same time, each did not make the same type or amount of contribution or each inventor did not make a contribution to the subject matter of every claim. Of course this leaves a number of questions unanswered, such as the question of how much and/or what kind of input from a putative inventor is required to amount to a “contribution”—in this case for a workable way to block PD-7 activation.

In this case, the panel agreed with Dana-Farber, that Ono was advocating for an unsupported “heightened standard of co-inventorship  wherein each inventor would be required to have conceived the complete invention and have participated in a particular moment of conception. The panel cited Burroughs Welcome Co. v. Barr – remember that early HIV case—for the standard that ”a joint invention is simply the product of a collaboration between two or more persons working together to solve the problem.” To be a joint inventor, one must make a contribution to the conception or reduction to practice of the invention that is “significant “ when that contribution is measured against the dimension of the full invention, and “do more than merely explain to the real inventors well-known concepts and/or the current state of the art.[citing Pannu v. Iolab Corp].”

The panel went on to state that while Freeman and Wood did not participate in “certain experiments that lead to conception”, this “does not negate their overall contributions throughout their collaboration with Dr. Honjo.” The panel also rejected Ono’s argument that the work from the collaboration was too speculative, prior to Honjo’s mouse data obtained in 2000: “An inventor need not know, however, that the invention will work for its intended purpose in order for conception to complete, as verification that an invention actually works is part of its reduction to practice” so long as one of skill in the art could understand the invention [citing Burroughs Welcome twice]….in vivo verification is not require for a conception to be definite and permanent.”

With respect to the Freeman/Wood patent filing, the panel reasoned that “Joint inventorship does not depend on whether a claimed invention is novel or unobvious over a particular researcher’s contribution. Collaboration and concerted effort are what result in joint inventorship.” With respect to the early publication by Wood/Freeman, the panel also ruled that “a collaborative enterprise is not negated by a joint inventor disclosing less that the total invention to others, especially  when, as here, the collaborators had worked together for around one year prior to the disclosure.”

Ono also attacked the significance of the contributions of Wood  and Freeman which the panel rebuffed, agreeing that the “core invention [is] blocking the PD1/PDL1 interaction so that the tumor cannot use the pathway to evade immune systems attack….Even under Ono’s view of the facts, knowledge of PD-1 was itself insufficient for Dr. Honjo to conceive of the method claimed [in one of the progeny patents]…Drs.. Feeman and Wood’s work linking PD-1 to its ligand and [the ligand’s] expression in tumors was a significant contribution to each of these patents’ conception.”

This appeal should have been easy for the court to resolve, given the length and results produced by the collaboration. However, If you have ever been involved in efforts to resolve an inventorship dispute between smart, hard-working scientists or engineers, you know how difficult sorting out their various contributions can be. Did one or the other make a “creative contribution” to at least one claim of the patent or application in question, or did they simply provide “good hands” that, e.g., carried out instructions provided by others? The approach taken in this decision may be of assistance the next time you find yourself in this much less than comfortable position.

© 2020 Schwegman, Lundberg & Woessner, P.A. All Rights Reserved.National Law Review, Volume X, Number 209
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About this Author

Warren Woessner, Registered Patent Attorney, Schwegman Lundberg Law firm
Shareholder

Warren Woessner is a registered patent attorney and a founding shareholder of Schwegman, Lundberg & Woessner. His practice focuses on chemical patent law, including biotechnology, pharmaceuticals, vaccines, medical treatments, diagnostics, and biofuels and agricultural chemistry, including related opinion and licensing matters.

Warren received his B.A. in chemistry (1966) from Cornell University, his Ph.D. (organic chemistry, 1971) and his law degree (J.D., cum laude, 1981) from the University of Wisconsin...

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