In Dana-Farber Cancer Institute v. Ono Pharmaceutical Co., LTD., the Federal Circuit Court of Appeals declined to heighten the established, conception-based standard for determining inventorship.

The patents at issue claim cancer treatment methods based on PD-1/PD-L1 pathway. PD-1 is a receptor present on T cells, which play a central role in immune response. When PD-1 binds to its ligands such as PD-L1, T cells are inhibited and do not attack cells that express the ligands. This interaction is normally used by healthy cells to shield themselves from any mistaken attack by T cells, but some tumor cells express the ligands to avoid T cells as well. The patents at issue utilize antibodies that target either PD-1 or PD-L1 to block the interaction, thus stimulating the immune response against tumor cells.

Dr. Honjo first discovered PD-1 in early 1990s. The patents at issue list him as an inventor and Ono as an assignee. However, Dr. Honjo was not without help. During his research, Dr. Honjo collaborated with Dr. Freeman and Dr. Wood. They held discussions, exchanged data, and presented results to each other. Dr. Freeman’s and Dr. Wood’s work was especially instrumental in identifying the ligands (PD-L1 and PD-L2) binding to the PD-1 receptor and high expression of the ligands in some tumor cells.

In 1999, Dr. Freeman and Dr. Wood filed a provisional patent application, disclosing modulation of the immune response via activating or blocking the PD-1/PD-L1 pathway. Notably, Dr. Honjo was not included as a joint inventor. Dr. Honjo later asked to be included as a joint inventor, but the Genetics Institute, the assignee of the provisional application at the time, refused.

In 2000, a researcher working for Dr. Honjo produced data suggesting a significant relationship between PD-L1 expression and tumor growth. Shortly afterward, Dr. Honjo stopped collaborating with Dr. Freeman and Dr. Wood.

In 2002, Dr. Honjo filed a patent application in Japan, which led to the patents at issue. This Japanese application did not include Dr. Freeman or Dr. Wood as joint inventors.

Dana-Farber, the assignee for Dr. Freeman’s rights, filed suit in 2015, alleging that Dr. Freeman and Dr. Wood should be included as joint inventors. In order to prove joint inventorship, one must:

(1) contribute to the conception or reduction to practice of the invention,

(2) make a contribution to the claimed invention that is not insignificant in quality when measured against the dimension of the invention, and

(3) do more than merely explain to the inventors well-known concepts and/or the current state of the art.

The Massachusetts District Court found for Dana-Farber, particularly crediting Dr. Freeman’s and Dr. Wood’s contributions in discovery of PD-L1 and their relationship with immune response, among others, as significant to the conception of the patents at issue.

On appeal, Ono challenged the district court’s legal analysis of conception in three ways. Ono first argued that the patents were based on the discovery of Dr. Honjo that was independent from Dr. Freeman’s and Dr. Wood’s contributions, because they did not participate in allegedly critical experiments that led to the conception of the invention. As the court noted, Ono effectively proposed that a joint inventor must conceive the complete invention and participate in a critical experiment leading to the conception of the invention.

Second, Ono noted that the patents were issued over Dr. Freeman’s and Dr. Wood’s 1999 provisional application, and argued that this meant the patents were novel and non-obvious over Dr. Freeman’s and Dr. Wood’s contributions, thus allegedly indicating that their contribution was not significant to the patents at issue.

Lastly, Ono argued that Dr. Freeman’s and Dr. Wood’s contributions should be deemed irrelevant to inventorship because their work with Dr. Honjo was published publicly before the conception of the invention, and thus could not be considered to be a significant contribution to the conception.

Ultimately, the Federal Circuit affirmed the district court’s decision.

On Ono’s first argument, the court found the Ono’s proposal to be inconsistent with the law, because the record indicated that Dr. Freeman’s and Dr. Wood’s work was a significant part of the basis that led to the critical experiments. In other words, contrary to Ono’s argument, the discovery of Dr. Honjo was not independent from Dr. Freeman’s and Dr. Wood’s work, and their contribution met the standard for finding joint inventorship. Further, the court noted that adopting such proposal would unnecessarily heighten the current standard for determining conception, which is deemed complete when an idea is definite and permanent enough that one skilled in the art can understand the invention.

Regarding Ono’s second argument, the court reasoned that the novelty and non-obviousness of the patents at issue did not negate any of Dr. Freeman’s and Dr. Wood’s contributions.

The court also found it impractical to adopt Ono’s third argument, given the reality of collaboration, which often spans for a long time and involve multiple contributions.

Ono further argued that the district court erred in its factual findings, but the Federal Circuit was not persuaded. Specifically, Ono alleged that Dr. Freeman’s and Dr. Wood’s contributions were not significant enough to amount to joint inventorship because their contribution was primarily on PD-L1, whereas the patents at issue claim the use of antibodies to PD-1. However, the court pointed to the fact that PD-1/PD-L1 interaction was the target for the antibodies, and without understanding this interaction, there would have been no conception of the patents at issue.

As an interesting side note, Dr. Honjo won the Nobel Prize in Physiology or Medicine in 2018 for his discovery, and credited Dr. Freeman as a major collaborator. In contrast, Ono tried to minimize Dr. Freeman’s contribution when arguing in front of the court, which the Federal Circuit certainly noticed: “it is not without interest that in his acceptance speech [Dr. Honjo] credited Dr. Freeman as a major collaborator in his work.”