Dana-Farber Cancer Institute, Inc. v. Ono Pharmaceutical Co., Ltd. et al.

Civil Action No. 15-13443-PBS
U.S. District Court, District of Massachusetts
May 17, 2019

Brief summary: DC determines Dana-Farber and Genetics Institute researchers to be co-inventors on the Honjo patents claiming cancer immunotherapy methods using anti-PD1 antibodies (e.g., BMS’s Opdivo® (nivolumab)).

Summary: Dana-Farber alleged Dr. Freeman (Dana-Farber) and Dr. Wood (GI) should have been named on Ono’s patents (the “Honjo patents”, to which BMS is exclusive licensee) directed to methods of cancer immunotherapy using anti-PD1 antibodies. The Honjo patents are described in the DC opinion as including US 7,595,048; 8,168,179; 8,728,474; 9,067,999; 9,073,994; and 9,402,899. The earliest priority date of the Honjo patents (on which Dr. Honjo (a 2018 Nobel Prize winner for this invention) is an inventor with two other individuals) is July 3, 2002. The dispute centers on whether the collaboration between Dr. Honjo at Kyoto University in Japan and Drs. Freeman and Wood at Dana-Farber and GI, respectively, between “at least October 1999[] until at least September 2000 through numerous meetings, joint authorship of scientific journal articles, and sharing of experimental results and ideas” (Dr. Honjo and Dr. Wood began their collaboration in September 1998) was of sufficient significance to qualify Drs. Freeman and Wood as inventors on the Honjo patents. The DC opinion explains that Dr. Honjo had complained to GI that he should have been included as an inventor on GI’s patent application naming Dr. Freeman in 1999 (an “angry exchange”), but how this argument resolved is not addressed in this opinion. The DC opinion provides much detail regarding the nature of the collaboration between the parties, including the discovery of the PD-1 receptor by Dr. Honjo in the early 1990s (published in 1992), Dr. Honjo’s knockout mouse experiments and 1999 Immunity publication describing “PD-1 as ‘a negative regulator of immune responses’”, Dr. Honjo’s unsuccessful ligand search, the efforts between Dr. Honjo and Dr. Wood to identify the PD-1 L1 ligand, Dr. Freeman’s discovery of “the 292 Ligand” (“B7-4”, ultimately “PD-L1”) and work with GI regarding the same (and provisional patent application regarding the same), Dr. Wood’s determination that “PD-1 and 292 bound together” (recognized by Dr. Honjo to be the result of a “strong collaboration”), collaboration meetings between Drs. Freeman, Wood and Honjo at GI, Dr. Freeman’s and Dr. Wood’s joint patent application claiming “methods of modulating the immune response via activating or blocking the PD-1/PD-L1 pathway” which they “did not tell Dr. Honjo about”, Dr. Freeman’s discovery of PD-L2 in 1999, the 2000 J. Exp. Med. including all three researchers as authors and including Dr. Freeman’s statement regarding “the possibility that some tumors may use PD-L1 to inhibit an anti-tumor response”, their independent development of anti-PD1 antibodies during 1999-2000, Dr. Honjo’s in vivo tumor model studies in 2000 using Dr. Freeman’s antibodies (Dr. Honjo stating “Needless to say, we will do [the experiments] as collaboration”), additional meetings in 2000, the dispute regarding inventorship on Drs. Freeman’s and Wood’s provisional application (“GI ultimately decided not to add Dr. Honjo”), the “effective[] end[]” of the collaboration in 2001, and Dr. Honjo’s / Ono’s patent application filing in 2002 (which led to the Honjo patents). The opinion also notes that Dr. Honjo acknowledged Dr. Freeman as a “[m]ajor outside collaborator” during his 2018 Nobel Prize lecture.

Medarex (acquired by BMS) then exclusively licensed the Honjo patents and began nivolumab clinical trials. The DC opinion explains that Dr. Freeman “learned about the ‘048 Patent in 2010” but “did not realize the patent used his discoveries until sometime between 2012 and 2014”, and Dana-Farber initiated the lawsuit in 2015 (no laches as explained near the end of the opinion, e.g., the suit was filed within six years of the ‘048 Patent issuance). Each party presented expert testimony regarding the contributions of each party to the research and their opinion regarding inventorship. The DC reviewed the law of joint inventorship (35 USC § 116(a), § 256(a) (correction of inventorship); Vapor Point, FC 2016 (“inventor…may bring a cause of action to correct inventorship”); Eli Lilly, FC 2004 (“only if he contributes to the conception”, need not be “equal in importance”); In re VerHoef, FC 2018 (“Conception ‘requires a ‘definite and permanent idea of an operative invention, including every feature…”, “essential feature”); Nartron, FC 2009 (not “an idea of a result to be accomplished”); Fallana, FC 2012 (“Collaboration is a key requirement…”); Symantec, FC 2008 (inventor testimony must be corroborated under “rule of reason”) (see also Apator, FC 2018, distinguished from this case)). Given all of the facts and legal standards described above, the DC determined that Drs. Freeman and Wood were co-inventors of the methods claimed in the Honjo patents (e.g., “There is no question that the three collaborated”, “clear and convincing evidence”, “while the fact that Dr. Freeman and Dr. Wood were not present during Dr. Iwai’s in vivo mouse tumor model experiments is relevant to determining how significant their contributions were to conception, it is not dispositive” (“Vanderbilt University is controlling” (FC 2010), “Dr. Freeman and Dr. Wood made significant contributions to conception…through their discovery of PD-L1 and PD-L2, their discoveries of blocking antibodies”, etc.). The DC therefore entered judgment in favor of Dana-Farber. FN1 explains that GI’s parent companies Wyeth and Pfizer settled with Defendants “on the eve of trial.”

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Patrick Halloran

Pat has a Ph.D. in Microbiology and Immunology from The University of Health Sciences / The Chicago Medical School (now the Rosalind Franklin Institute (North Chicago, IL) (1994)). He also completed post-doctoral studies at The National Cancer Institute (1994-1996) where he developed novel approaches for gene therapy of melanoma. Pat has been an attorney (IL) since 1999 after graduating from Chicago-Kent College of Law, which was recently ranked as one of the top five law schools for Intellectual Property in the U.S. (U.S. News and World Report link). Pat also has a B.A. in Biology from Augustana College (Rock Island, IL; 1989) where he was on two NCAA Division III National Championship football teams (1985, 1986). He currently resides in Center Valley, PA.