Holding: In Dana-Farber Cancer Institute, Inc. v. Ono Pharm. Co., Ltd., --F.3d-- (Fed. Cir. July 14, 2020), the U.S. Court of Appeals for the Federal Circuit (Judges LOURIE, Newman, and Stoll) affirmed the District Court's decision that Freeman and Wood should be added as co-inventors to six cancer treatment patents owned by Ono Pharmaceutical ("Ono").

Background: Ono's patents claim methods of treating cancer by administering antibodies that target either the PD-1 receptor or its PD-L1 ligand and block the receptor-ligand interaction. The patents issued with four co-inventors, including Honjo. The issue in this case was whether Freeman and Wood should also be deemed co-inventors of those patents.

Honjo worked at Kyoto University in the 1990s and discovered the PD-1 receptor. Using knockout mouse models, he and a colleague demonstrated that the receptor was involved in immune-system inhibition and published their work in August 1999 in Immunity.

In 1998 Honjo met with Wood, a researcher at Genetics Institute who believed that the PD-1 receptor could be a candidate for antibody therapy development. Honjo and Wood began a collaboration to identify the PD-1 ligand, and Honjo shared PD-1 reagents and a confidential draft of the Immunity article with Wood. Meanwhile, earlier in 1998, Freeman, a researcher at Dana-Farber, identified the "292" sequence as a potential PD-1 ligand.

The three scientists then began sharing information. Wood and Freeman worked together and determined that PD-1 binds to 292, and so informed Honjo. The three scientists dubbed 292 "PD-L1" and Honjo sent Wood anti-PD-1 antibodies for further experimentation. Freeman contacted Honjo at this point, proposing a possible collaboration researching the PD-1/PD-L1 pathway.

At a meeting in October 1999, Wood disclosed that PD-L1 antibodies inhibited the PD-1/PD-L1 interaction; Freeman disclosed that the 292 sequence was from a human ovarian tumor; and Honjo disclosed his unpublished knockout mouse data, indicating that PD-1 inhibits the immune response. After the meeting, Freeman and Wood filed a provisional patent application, but did not list Honjo as an inventor.

The three scientists then worked together on a journal article about PD-L1. In a final round of edits in April 2000, Freeman added a sentence to the article stating that PD-L1 was also expressed in cancers and that some tumors might use PD-L1 to inhibit an antitumor immune response.  By May 2000, Wood, Freeman, and Honjo were discussing the development of anti-PD-L1 antibodies and the possible use of those antibodies in treating cancer.

In October 2000, Iwai, a named co-inventor on the patents at issue, generated data in knockout mice, suggesting that mouse melanoma tumors expressing PD-L1 grow faster than tumors without PD-L1 expression. This is the point in time that Ono identified as when the named inventors jointly conceived of the claimed inventions.

As more data were generated after October 2000, Honjo stopped sharing results with Freeman and Wood. However, the three met one final time in April 2001. In 2002, Honjo filed a patent application in Japan and did not include Freeman and Wood as co-inventors. All of the patents-at-issue in this case claim priority to this Japanese patent application. 

Dana-Farber filed suit in the District of Massachusetts seeking to add Freeman and Wood as co-inventors on Honjo's U.S. patents under 35 U.S.C. §256(b). Dana-Farber Cancer Inst., Inc. v. Ono Pharm. Co., 379 F. Supp. 3d 53 (D. Mass. 2019). The district court credited, as contributions significant to the conception of all six patents,

  1. Freeman and Wood's discovery of the PD-L1 ligand,
  2. Wood's discovery that PD-1/PD-L1 binding inhibits the immune response,
  3. Freeman and Wood's discovery that anti-PD-1 and anti-PD-L1 antibodies can block the pathway's inhibitory signal, and
  4. Freeman's immunohistochemistry experiments confirming PD-L1 expression in various tumors.

 Id. at *8. Accordingly, the district court ordered that Freeman and Wood be added as co-inventors to the patents at issue.

On appeal, Ono urged that the work done by Freeman and Wood did not rise to the level of inventive contributions because:

  1. their experiments were not done in vivo and were too far removed from the claimed methods of treatment;
  2. the patents at issue were issued over Freeman and Wood's 1999 provisional application; and
  3. their work with Honjo had been published in October 2000 before conception of the patented inventions. 

Id. at *9-10.

Federal Circuit Affirmed the District Court Decision: The Federal Circuit began its analysis by noting that, under 35 U.S.C. § 116(a), "[i]nventors may apply for a patent jointly even though (1) they did not physically work together or at the same time, (2) each did not make the same type or amount of contribution, or (3) each did not make a contribution to the subject matter of every claim of the patent." Id. at *9.

Applying this standard, the Federal Circuit concluded that Ono improperly asked the court to adopt an unnecessarily heightened requirement for inventorship. Id. at *10.  According to the Federal Circuit, "the statute and our case law make clear that joint inventors need not contribute to all aspects of a conception." Id. at *11. To claim co-inventorship, Freeman and Wood did not need to be present for or to have participated in all the experiments that led to the conception of the claimed inventions, as long as they made inventive contributions throughout their collaboration with Honjo. Id.

In addition, the Federal Circuit pointed out that, although Iwai's work provided important in vivo data, "in vivo verification is not required for a conception to be definite and permanent." Id. at *11-12. In this case, Iwai's work was conducted after Freeman had already shown expression of PD-L1 in human tumors and thus the Federal Circuit concluded that PD-L1's potential utility in treating human cancers was developed jointly with Freeman before Iwai's work.

Regarding Ono's argument that Freeman's and Wood's contributions were not relevant to the claimed invention because the Honjo's patents were issued over their 1999 provisional application, the Federal Circuit stressed that "joint inventorship does not depend on whether a claimed invention is novel or nonobvious over a particular researcher's contribution." Id. at *12. The Federal Circuit also refused to hold categorically that "research made public before the date of conception of a total invention cannot qualify as a significant contribution to conception of the total invention." Id.  According to the Court, collaboration generally spans a period of time and may involve multiple contributions, and "there is no principled reason to discount genuine contributions made by collaborators because portions of that work were published prior to conception for the benefit of the public." Id. at *12-13.  The Court concluded that, in this case, publication of a portion of the complex invention did not defeat joint inventorship of that invention. Id. at *13.

Ono also argued the district court erred in several aspects of its factual analysis, but the Federal Circuit found the district court's factual conclusions not clearly erroneous, noting that "[e]ven under Ono's view of the facts, knowledge of PD-1 was itself insufficient for Honjo to conceive of the method claimed in the [patents at issue]." Id. at *15.

The Federal Circuit thus affirmed the district court's decision, concluding that "discovery of PD-1 in a vacuum was insufficient for conception" and that "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." Id.

Take-Away: Patents resulting from collaborations among various researchers in different institutions may have joint inventorship issues.  When an issued patent does not properly include all inventors, patent ownership may be impacted, which in turn impacts who has the right to make, use, offer to sell, and sell the claimed invention, as well as who is needed to enforce the patent.

The Federal Circuit reiterated in this case that neither the relevant statute nor the case law requires each inventor to have made the same type or amount of contribution to be deemed a co-inventor. This case also confirms that, for a patent reciting a method of treatment using an antibody against a novel target, researchers' contributions to conception are not necessarily limited to in vivo data if other work suggested the utility of the antibody for the recited treatment. 

In addition, a co-inventor's prior public disclosure of certain aspects of the invention does not necessarily negate his/her contributions to the claimed invention, as long as the prior public disclosures did not simply inform another about the state of the prior art.  

Thus, when naming co-inventors during prosecution, patent applicants need to carefully evaluate the contribution of each researcher to the claimed invention, including whether there was any contribution from earlier research that led to later verification of the conception and the nature of the researchers' collaboration.

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