In Dana-Farber Cancer Institute, Inc. v. Ono Pharmaceutical Co. Ltd, the Federal Circuit held that two scientists, Dr. Gordon Freeman and Dr. Clive Wood, should be included as joint inventors, along with Dr. Tasuku Honjo for patents related to immunotherapy for treating cancer. Identifying foundational discoveries underlying a patent claim could be considered a significant contribution that may rise to the level of inventorship even though the claims do not recite such discoveries. The decision clarifies inventorship rules in the context of pioneering therapeutic work, and suggests that no necessary contribution can be ignored in the inventorship analysis, even if the contribution was independently published before the application for patent.

Dr. Honjo discovered PD-1, a protein expressed on the surface of T-cells, in the early 1990s and was awarded the Nobel Prize in Physiology or Medicine 2018 for this work. The claims of the patents at issue recite using antibodies that target either the PD-1 receptor or its PD-L1 ligand, thereby blocking the receptor-ligand interaction and stimulating an immune response against tumor cells. By the late 1990s, Dr. Honjo, Dr. Freeman, and Dr. Wood had begun working together to study the PD-1/PD-L1 pathway. By 2001, the sharing of information between them had ended.

The United States District Court for the District of Massachusetts found the following as “significant” contributions to the conception of the patents at issue:

• Freeman and Wood discovered the PD-L1 ligand;
• Wood discovered that PD-1/PD-L1 binding inhibits the immune response;
• Freeman and Wood discovered anti-PD-1 and anti-PD-L1 antibodies can block the pathway’s inhibitory signal; and
• Freeman experimentally confirmed PD-L1 expression in tumors.

Thus, the district court concluded that Drs. Freeman and Wood should be added as inventors. Ono Pharmaceutical Co., its licensee Bristol-Myers Squibb Co., and Dr. Honjo (collectively, “Ono”) appealed.

The Federal Circuit stated that a joint inventor must “contribute in some significant manner” but “need not contribute to all aspects of a conception.” Moreover, “[i]nventorship of a complex invention may depend on partial contributions to conception over time.” The court further noted that “publication of a portion of a complex invention does not necessarily defeat joint inventorship” but cautioned that an earlier publication could be a hazard to patentability.

Despite that the claims of one patent at issue were directed to using anti PD-1 antibodies and did not recite the PD-L1 ligand, the Federal Circuit agreed with the district court’s finding that “knowing the structure and function of PD-L1 was essential to all the claimed inventions.” The court reasoned that, “[u]nless one also knows that the PD-1 receptor binds to at least one ligand . . . such as PD-L1, there would be no reason to use anti-PD-1 antibodies.” Thus, the claims “need not explicitly recite PD-L1 for research on PD-L1 to have a significant contribution to conception of the invention.” Each of the remaining patents at issue recited using anti-PD-1 or anti-PD-L1 antibodies, and the court maintained that the “discovery of PD-1 in a vacuum was insufficient for conception.” Thus, the Federal Circuit concluded that “Drs. Freeman and Wood’s work linking PD-1 to its ligand and expression in tumors was a significant contribution to each of these patents’ conception” and affirmed the district court’s holding. Thus, a claim to a method of treatment may invoke inventorship for those who discovered the mechanism by which the treatment has an effect.

Inventorship continues to be a highly factually-dependent analysis. In the pharmaceutical development context, this case indicates that validating a new, and complex, target and connecting that target to a use could be significant contributions that may give rise to inventorship. Prudent record maintenance during the course of the research also could be critical evidence to demonstrate a contribution, particularly where research develops over time. Additionally, innovators should be cautioned that carefully drafted research agreements should be in place before any collaboration begins.

The Dana-Farber Cancer Institute, Inc. v. Ono Pharmaceutical Co. Ltd., Fed. Cir. 19-2050 (July 14, 2020) opinion can be found here.