United States Court of Appeals 

for the Federal Circuit ______________________

DANA-FARBER CANCER INSTITUTE, INC.,

Plaintiff-Appellee

v.

ONO PHARMACEUTICAL CO., LTD., TASUKU 

HONJO, E.R. SQUIBB & SONS, L.L.C., BRISTOLMYERS SQUIBB COMPANY,

Defendants-Appellants

______________________

2019-2050

______________________

Appeal from the United States District Court for the 

District of Massachusetts in No. 1:15-cv-13443-PBS, 

United States District Judge Patti B. Saris.

______________________

Decided: July 14, 2020

______________________

DONALD ROSS WARE, Foley Hoag LLP, Boston, MA, argued for plaintiff-appellee. Also represented by SARAH S.

BURG, BARBARA A. FIACCO. 

 SETH P. WAXMAN, Wilmer Cutler Pickering Hale and 

Dorr LLP, Washington, DC, argued for defendants-appellants. Also represented by STEVEN JARED HORN, THOMAS 

SAUNDERS; MATTHEW TYMANN, Los Angeles, CA; DIANNE B.

ELDERKIN, STEVEN D. MASLOWSKI, MATTHEW A. PEARSON, 

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Akin, Gump, Strauss, Hauer & Feld, LLP, Philadelphia, 

PA. 

 ______________________

Before NEWMAN, LOURIE, and STOLL, Circuit Judges.

LOURIE, Circuit Judge. 

Ono Pharmaceutical Co. Ltd., Tasuku Honjo, E.R. 

Squibb & Sons, L.L.C., and Bristol-Myers Squibb Co. (collectively, “Ono”) appeal from the judgment of the United 

States District Court for the District of Massachusetts after a bench trial ordering that Dr. Gordon Freeman and Dr. 

Clive Wood be added to U.S. Patents 7,595,048 (“the ’048 

patent”), 8,168,179 (“the ’179 patent”), 8,728,474 (“the ’474 

patent”), 9,067,999 (“the ’999 patent”), 9,073,994 (“the ’994 

patent”), and 9,402,899 (“the ’899 patent”) as co-inventors. 

Dana-Farber Cancer Inst., Inc. v. Ono Pharm. Co., 379 F. 

Supp. 3d 53 (D. Mass. 2019) (“Decision”). Because we conclude that the district court did not err in its inventorship 

determination, we affirm. 

BACKGROUND

This appeal presents an inventorship dispute over 

groundbreaking work in the field of cancer treatment. 

Each patent at issue claims a method of treating cancer by 

administering antibodies targeting specific receptor-ligand 

interactions on T cells. 

The human immune system comprises many different 

cell types, but two types of those cells are relevant here: 

dendritic cells and T cells. Dendritic cells detect pathogens 

and present antigens—proteins from a pathogen or tumor—to T cells. T cells have a variety of functions but, as 

relevant here, are responsible for processing information to 

develop an immune response in the body using receptors 

on their surfaces. The primary receptor on a T cell, the T 

cell receptor, can bind to antigens to activate an immune 

response. But a signal sent to a T cell receptor will not 

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activate the T cell unless a ligand binds to one of its costimulatory receptors, such as CD28. CD28 has two ligands, B7-1 and B7-2, which are expressed in dendritic cells 

that have detected infection or cancer. For a T cell to activate an immune response, two things must happen: (1) an 

antigen on a dendritic cell must bind to the T cell receptor, 

and (2) a B7 ligand on the dendritic cell must bind to the 

CD28 receptor on the T cell. In the absence of an infection 

or cancer, dendritic cells do not express B7 ligands on their 

surface thus blocking an immune response. B7 ligands also 

bind to an inhibitory receptor called CTLA-4, which is only 

expressed in highly activated T cells. B7 ligands bind more 

tightly to CTLA-4 than to CD28, so if both receptors are 

being expressed, CTLA-4 prevents the B7 ligands from activating the T cell through the CD28 receptor. 

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, either PD-L1 or PDL2, the T cell is inhibited and does not attack the cell expressing the ligand. Expression of the PD-1 ligands in 

healthy cells generally shields 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 their expression of the PD-L1/L2 ligands. 

The appeal raises the question whether Drs. Freeman 

and Wood should be deemed inventors of the subject matter 

of the ’048, ’179, ’474, ’999, ’994, and ’899 patents alongside 

Dr. Tasuku Honjo. Essential to this determination is a recounting of each researcher’s work and the nature of their 

collaboration. 

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Dr. Honjo, a professor at Kyoto University’s medical 

school, discovered the PD-1 receptor in the early 1990s. He 

isolated its DNA sequence and began working with the protein in mouse models with Dr. Nagahiro Minato, a colleague studying tumor immunology. Using knockout mice 

(wherein the PD-1 gene is not expressed), they discovered 

that mice without PD-1 showed symptoms typical of autoimmune disease, suggesting that the receptor was involved 

in immune-system inhibition. Based on its structure, 

Dr. Honjo believed at that time that PD-1 was in the same 

family of proteins as the inhibitory receptor CTLA-4. 

Drs. Honjo and Minato submitted their research for publication, and their work was published in Immunity in August 1999.

In mid-1998, Dr. Honjo enlisted a graduate student, 

Dr. Yoshiko Iwai, to conduct studies on PD-1 with knockout 

mice and human tumor cell lines. Dr. Iwai found binding 

of the PD-1 protein in a variety of cells, including in tumor 

cells, but she did not identify the molecule that was binding 

to the receptor. She also recognized that her experiments 

may have yielded false positives because she used a specific 

fusion protein. Her work did not continue at that time because she took a leave of absence because of illness.

In September 1998, Dr. Honjo met with representatives from Ono, now an assignee of Dr. Honjo’s rights in the 

instant patents, and the Genetics Institute, who connected 

him to Dr. Wood, a researcher at Genetics Institute. They

discussed Dr. Honjo’s work with PD-1, and Dr. Wood 

agreed to collaborate with Dr. Honjo to find the PD-1 ligand. Dr. Wood believed that the PD-1 receptor could be a 

candidate for antibody therapy development, and accordingly Dr. Honjo shared with him PD-1 reagents and a confidential draft of the Immunity article. 

In July 1998, Dr. Freeman, a researcher at Dana-Farber, was studying novel B7 ligands. He ran a search in the 

BLAST database for a sequence of 208 amino acids that 

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forms part of the binding portion of the B7-1 molecule. The 

search yielded 12 results—two of which were from human 

ovarian tumors—and Dr. Freeman began to investigate the 

sequence further, titling it “292” after its label in the database. 

At this point, the timelines converge. Drs. Wood, Freeman, and Honjo began sharing information directly. 

Drs. Wood and Freeman began working together to determine whether PD-1 binds to 292, and Dr. Wood informed 

Dr. Honjo that it does. The three dubbed 292 “PD-L1” and 

ran further experiments. Dr. Wood sent Dr. Honjo plans 

for a journal article, and Dr. Honjo sent Dr. Wood antiPD-1 antibodies for further experimentation. Dr. Freeman 

emailed Dr. Honjo for the first time at this point, discussing 

the possibility of a research collaboration on the 

PD-1/PD-L1 pathway. 

The collaboration culminated in a meeting in Cambridge, Massachusetts in October 1999. At the meeting, 

Dr. Wood disclosed that PD-1 and CTLA-4 had similar 

structures and that PD-L1 antibodies inhibited the 

PD-1/PD-L1 interaction. Dr. Freeman disclosed that 292 

was from a human ovarian tumor and that PD-L1 shares 

20% of its amino acid sequence with B7-1 and B7-2 but does 

not bind to either CD28 or CTLA-4. Dr. Honjo disclosed his 

unpublished knockout mouse data indicating that PD-1 inhibits the immune response. 

After the meeting, the three began exchanging reagents. Dr. Honjo ran in vitro experiments on the pathway 

indicating that it inhibited the immune response, using 

knockout mouse cells as a control. Drs. Freeman and Wood 

filed a provisional patent application disclosing modulation 

of the immune response via activating or blocking the PD1/PD-L1 pathway, but did not list Dr. Honjo as an inventor.

In the fall of 1999, Dr. Freeman conducted a second 

BLAST search and identified another B7-like molecule 

that shares 38% of its protein structure with PD-L1. Over 

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the next year, Dr. Freeman conducted a number of experiments on this ligand, which he labeled PD-L2.

In January 2000, Dr. Freeman asked Dr. David Dorfman, a pathologist at the Brigham and Women's Hospital, 

and Dr. Julia Brown, a new postdoctoral researcher, to test 

both normal and tumor tissues and determine whether PDL1 was expressed by them. Dr. Dorfman studied numerous 

cell lines and found high PD-L1 expression in tumors, including squamous cell carcinoma of the tongue, breast lobular carcinoma, lung and colon adenocarcinoma, and 

anaplastic large cell lymphoma. These immunohistochemistry results were not published until 2003.

In March 2000, Dr. Freeman emailed Dr. Honjo to tell 

him about PD-L2 and to send its sequence. Drs. Honjo, 

Freeman, and Wood then worked on a journal article documenting their discoveries concerning PD-L1, and, in a final 

round of edits in April 2000, Dr. Freeman added a sentence 

to the paper stating that PD-L1 was also expressed in cancers and that some tumors may use PD-L1 to inhibit an 

antitumor immune response. This article was published in 

the Journal of Experimental Medicine on October 2, 2000.

Drs. Wood, Freeman, and Minato all separately developed antibody candidates. In March 2000, Drs. Wood and 

Honjo presented results of their PD-1/PD-L1 collaborative

research at a conference. Dr. Iwai also resumed her knockout mice studies. By May 2000, Drs. Wood, Freeman, and 

Honjo were discussing their development of anti-PD-L1 antibodies and the possible use of those antibodies in treating 

cancer. 

In June 2000, Dr. Honjo learned of the 1999 provisional 

application filed by Drs. Wood and Freeman, and challenged his exclusion as an inventor. By September, the 

three had met again in Cambridge and Drs. Wood and 

Freeman presented the results of their research on PD-L2. 

Dr. Honjo presented some new data from Dr. Iwai’s knockout mice. 

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In October, Dr. Iwai had generated data suggesting 

that mouse melanoma tumors expressing PD-L1 grow 

faster than tumors without PD-L1 expression. Ono identifies October 2000 as the date Drs. Honjo, Iwai, and Minato 

conceived the claimed inventions. As more data were generated by the Iwai experiments, Dr. Honjo stopped sharing 

results with Drs. Freeman and Wood. The three met one 

final time in April 2001. 

Meanwhile, Dr. Honjo’s attorneys were pursuing his inventorship claim, but Genetics Institute, the assignee of 

Drs. Freeman and Wood’s patents, and its attorneys declined to voluntarily add him to their patents. Genetics Institute stated that Dr. Honjo could pursue his inventorship 

claim at the PTO. Inventorship of those patents is not at 

issue here. 

In 2002, Dr. Honjo then filed his own patent application in Japan, disclosing results from Drs. Honjo, Iwai, and 

Minato’s experiments. Each patent at issue in this case 

claims priority from Dr. Honjo’s Japanese patent application; none include Drs. Freeman and Wood as inventors. 

Because Dr. Freeman is an employee of Dana-Farber, 

Dana-Farber is presumably the assignee of any rights he 

has as an alleged inventor of any of the patents in suit. 

Pfizer, which purchased Genetics Institute, is presumably 

the assignee of any rights Dr. Wood has in the patents, but 

Pfizer has transferred its potential interest in the patents 

to Ono. None of these relationships is at issue here. 

Dr. Freeman allegedly learned about the ’048 patent in 

2010 but did not pursue litigation until 2015. Dr. Wood 

may have known of the patents but did not get involved 

until Dana-Farber filed this suit on behalf of Dr. Freeman. 

In 2018, Dr. Honjo won the Nobel Prize in Physiology or 

Medicine, and it is not without interest that in his acceptance speech he credited Dr. Freeman as a major collaborator in his work. 

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The parties’ inventorship dispute began in the United 

States District Court for the District of Massachusetts. 

Dana-Farber brought suit alleging that Drs. Freeman and 

Wood should be added as inventors on Dr. Honjo’s patents. 

Dana-Farber presented an eight-point theory justifying

Drs. Freeman and Wood’s inventorship: (1) Dr. Freeman 

found the 292 sequence; (2) Drs. Freeman and Wood jointly 

disclosed PD-L1; (3) Drs. Freeman and Wood discovered 

that PD-1/PD-L1 binding inhibits T cell activation; (4) 

Dr. Freeman contributed the idea of treating cancer by 

blocking the pathway in his April 2000 edits to the researchers’ journal article; (5) Dr. Freeman provided reagents that Dr. Iwai used in her mouse model; (6) Dr. 

Freeman, through Dr. Dorfman, discovered that human 

PD-L1 is expressed across a number of tumors; (7) 

Drs. Freeman and Wood discovered PD-L2; and (8) 

Drs. Freeman and Wood developed relevant antibodies. 

In a 111-page opinion, the district court considered 

each of Dana-Farber’s points. Ultimately, the court credited Drs. Freeman and Wood’s discovery of the PD-L1 ligand, Dr. Wood’s discovery that PD-1/PD-L1 binding 

inhibits the immune response, Drs. Freeman and Wood’s

discovery that anti-PD-1 and anti-PD-L1 antibodies can 

block the pathway’s inhibitory signal, and Dr. Freeman’s 

immunohistochemistry experiments confirming PD-L1 expression in various tumors as contributions significant to 

the conception of all six patents. 

Ono appealed, and we have jurisdiction under 28 

U.S.C. § 1295(a)(1).

DISCUSSION

District courts may order the correction of patent inventorship by the U.S. Patent and Trademark Office “on 

notice and hearing of all parties concerned.” 35 U.S.C. 

§ 256(b). “[A] valid patent requires correct inventorship.” 

In re VerHoef, 888 F.3d 1362, 1365 (Fed. Cir. 2018), as 

amended (May 7, 2018). Inventorship is a question of law 

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reviewed de novo, but the district court’s underlying findings of fact are reviewed for clear error. Vapor Point LLC 

v. Moorhead, 832 F.3d 1343, 1348 (Fed. Cir. 2016) (citing 

Gen. Elec. Co. v. Wilkins, 750 F.3d 1324, 1329 (Fed. Cir. 

2014) and then Trovan, Ltd. v. Sokymat SA, Irori, 299 F.3d 

1292, 1301 (Fed. Cir. 2002)).

35 U.S.C. § 116(a) provides the standard for joint inventorship: 

When an invention is made by two or more persons 

jointly, they shall apply for patent jointly and each 

make the required oath, except as otherwise provided in this title. Inventors 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.

Ono challenges the district court’s decision on two bases: (1) the district court’s legal analysis of conception, and 

(2) the district court’s factual findings regarding inventorship. We address each argument in turn.

A

Ono argues that as a matter of law the district court 

erred by relying on contributions of Drs. Freeman and 

Wood that were too far removed from the claimed subject 

matter of the patents; it also argues that these contributions were made public and were hence in the prior art before the alleged conception. In Ono’s view, the patents 

claim specific methods of treating cancer using PD-1 or PDL1 blocking antibodies, and Drs. Honjo and Minato discussed the possible use of PD-1 for treating cancer in October 2000 in conjunction with data received from Dr. Iwai’s 

knockout mice experiments. Thus, Ono submits, these experiments, performed independently of Drs. Freeman or 

Wood, were what led directly to the conception of the 

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claimed inventions, and the previous work was at most 

speculative because it was not in vivo. Ono also notes that 

the patents were issued over Drs. Freeman and Wood’s 

1999 provisional application as evidence that the patents

claim treatments that were novel and nonobvious over Drs. 

Freeman’s and Wood’s alleged contributions. 

Ono also argues that Drs. Freeman’s and Wood’s alleged inventive contributions should be deemed irrelevant 

to inventorship because their work with Dr. Honjo was 

published in October 2000 in the Journal of Experimental 

Medicine before conception of the patented inventions. 

Ono urges us to adopt a legal rule that once a contribution 

is made public, it “no longer qualifies as a significant contribution to conception.” Appellants’ Br. 39. 

Dana-Farber responds that Ono offers an erroneous

view of the law. According to Dana-Farber, Ono’s rule 

would require each joint inventor to individually have conceived the complete invention and have participated in a 

particular moment of conception, which is inconsistent 

with law. 

We agree with Dana-Farber. Ono asks us to adopt an 

unnecessarily heightened inventorship standard. “[A] joint 

invention is simply the product of a collaboration between 

two or more persons working together to solve the problem 

addressed.” Fina Oil & Chem. Co. v. Ewen, 123 F.3d 1466, 

1473 (Fed. Cir. 1997) (citing Burroughs Wellcome Co. v. 

Barr Labs., Inc., 40 F.3d 1223, 1227 (Fed. Cir. 1994)). To 

be a joint inventor, one must:

(1) contribute in some significant manner 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 that contribution is measured against the dimension of the 

full invention, and (3) do more than merely explain 

to the real inventors well-known concepts and/or 

the current state of the art.

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Pannu v. Iolab Corp., 155 F.3d 1344, 1351 (Fed. Cir. 1998); 

quoted in VerHoef, 888 F.3d at 1366. There is no “explicit 

lower limit on the quantum or quality of inventive contribution required for a person to qualify as a joint inventor.” 

Eli Lilly & Co. v. Aradigm Corp., 376 F.3d 1352, 1358 (Fed. 

Cir. 2004) (quoting Fina Oil, 123 F.3d at 1473). “People 

may be joint inventors even though they do not physically 

work on the invention together or at the same time, and 

even though each does not make the same type or amount 

of contribution.” Burroughs Wellcome, 40 F.3d at 1227 (citing 35 U.S.C. § 116). 

Ono attacks the inventorship case for Drs. Freeman 

and Wood on the ground that they failed to participate in 

certain experiments that led to the conception of the 

claimed invention, but the statute and our case law make 

clear that joint inventors need not contribute to all aspects 

of a conception. See, e.g., Eli Lilly, 376 F.3d at 1359–59; 35 

U.S.C. § 116(a). That Drs. Freeman and Wood were not 

present for or participants in all the experiments that led 

to the conception of the claimed inventions does not negate 

their overall contributions throughout their collaboration 

with Dr. Honjo.

Ono’s argument that work from Drs. Honjo, Freeman, 

and Wood’s collaboration was too speculative until the October 2000 knockout mice studies is likewise misguided. 

Conception is the touchstone of the joint inventorship inquiry, Sewall v. Walters, 21 F.3d 411, 415 (Fed. Cir. 1994), 

and conception is complete when an idea is definite and 

permanent enough that one of skill in the art could understand the invention, Burroughs Wellcome, 40 F.3d at 1228. 

An inventor need not know, however, that an invention will 

work for its intended purpose in order for conception to be 

complete, as verification that an invention actually works 

is part of its reduction to practice. Id. (citing Applegate v. 

Scherer, 332 F.2d 571, 573 (CCPA 1964) and Oka v. 

Youssefyeh, 849 F.2d 581, 584 n.1 (Fed. Cir. 1988)). While 

Dr. Iwai’s work provided important in vivo data, in vivo

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verification is not required for a conception to be definite 

and permanent. See In re Isaacs, 347 F.2d 887, 889 (CCPA 

1965) (holding that in vivo testing was not required to establish utility for claims to interferon). Moreover, the record is clear that Dr. Iwai’s work was conducted after Dr. 

Freeman had shown expression of PD-L1 in human tumors 

and Dr. Honjo had shown that PD-L1 expression causes tumor growth, so as a factual matter, PD-L1’s potential utility in treating human cancers was developed jointly with 

Dr. Freeman before Dr. Iwai’s work. 

Ono also argues that the Honjo patents were issued 

over Drs. Freeman and Wood’s 1999 provisional patent application, so the latter contributions were thus not significant to the dispute over inventorship of Dr. Honjo’s

patents. As a factual matter, it is unclear that Drs. Freeman and Wood’s contributions to the inventions are co-extensive with the disclosure of their provisional application. 

Regardless, joint inventorship does not depend on whether 

a claimed invention is novel or nonobvious over a particular researcher’s contribution. Collaboration and concerted 

effort are what result in joint inventorship. Eli Lilly, 376 

F.3d at 1359. The novelty and nonobviousness of the 

claimed inventions over the provisional application are not 

probative of whether the collaborative research efforts of 

Drs. Honjo, Freeman, and Wood led to the inventions

claimed here or whether each researcher’s contributions 

were significant to their conception. 

Ono also urges us 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. Such a rule would ignore the 

realities of collaboration, especially that collaboration generally spans a period of time and may involve multiple contributions. It is certainly true that simply informing 

another about the state of the prior art does not make one 

a joint inventor. Hess v. Advanced Cardiovascular Sys., 

Inc., 106 F.3d 976, 981 (Fed. Cir. 1997) (holding that 

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explaining the state of the art and providing well-known 

information found in textbooks was insufficient for joint inventorship). But a collaborative enterprise is not negated 

by a joint inventor disclosing ideas less than the total invention to others, especially when, as here, the collaborators had worked together for around one year prior to the 

disclosure, and the disclosure occurred just a few weeks 

prior to conception. Inventorship of a complex invention 

may depend on partial contributions to conception over 

time, 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. Earlier publication of an invention is obviously a potential hazard to patentability, but publication of 

a portion of a complex invention does not necessarily defeat 

joint inventorship of that invention, and it does not here. 

B

Next, Ono raises a series of challenges to the district 

court’s factual analysis for each patent. We begin where 

Ono focuses the majority of its argument, the ’474 patent.

i. ’474 patent

Claim 1 of the ’474 patent recites a “method for treatment of a tumor in a patient, comprising administering to 

the patient a pharmaceutically effective amount of an antiPD-1 monoclonal antibody.” ’474 patent col. 25 ll. 13–15. 

According to Ono, Dr. Freeman’s alleged contribution to 

discovering PD-L1 was locating the 292 sequence in the 

BLAST database, but he played no meaningful role in the 

discovery that the PD-1/PD-L1 pathway is inhibitory. Ono 

also contends that Dr. Freeman’s work is not a significant 

contribution to the invention of the ’474 patent because the 

’474 patent claims rely on anti-PD-1 antibodies, not PD-L1 

antibodies. 

Ono argues that Dr. Wood likewise should not be credited as a joint inventor on the ’474 patent because his work 

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on the PD-L1 pathway was not a significant contribution 

to the claims. Ono submits that the district court overstated Dr. Wood’s contributions and that Dr. Wood’s work 

merely confirmed information that Dr. Honjo had already 

discovered. 

Dana-Farber responds that Ono failed to argue that 

the inventors’ contributions differ from patent to patent before the district court. According to Dana-Farber, “the 

claimed methods are all based on conception of the same 

core invention: blocking the PD-1/PD-L1 interaction so that 

the tumor cannot use the pathway to evade immune system attack.” Appellees’ Br. 41 (emphasis omitted). DanaFarber cites the district court’s fact finding that knowing 

the structure and function of PD-L1 was essential to all the 

claimed inventions.

We agree with Dana-Farber, and with the district 

court, that Drs. Freeman and Wood are joint inventors of 

the ’474 patent. The ’474 patent claims use of anti-PD-1 

antibodies in treating cancer and does not explicitly mention PD-L1. But PD-1 is just a receptor. Unless one also 

knows that the PD-1 receptor binds to at least one ligand

that inhibits the immune response, such as PD-L1, there 

would be no reason to use anti-PD-1 antibodies to treat tumors. The ’474 patent claims need not explicitly recite PDL1 for research on PD-L1 to have been a significant contribution to conception of the invention. 

The record certainly confirms this reality. The district 

court credited testimony from Dana-Farber’s expert, Dr. 

Kenneth Murphy, that not all antibodies that bind to a receptor or ligand block the signal. Ono’s expert, Dr. Mark 

Greene, did not contest that Dr. Honjo needed to understand the receptor-ligand interaction to develop effective 

therapeutic antibodies. But even apart from expert testimony, Dr. Honjo’s own efforts underscore the importance 

of understanding the receptor-ligand relationship to conception. In 1992, Dr. Honjo discovered PD-1 and theorized 

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that it played a role in inhibiting the immune response. 

But despite having this knowledge, Dr. Honjo still enlisted 

collaboration with the Genetics Institute to search for ligands for PD-1. 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 the ’474 patent. 

It is clear based on the record that Drs. Freeman and 

Wood both contributed to conception of the ’474 patent. Dr. 

Freeman connected the 292 sequence to PD-1 and directed 

important immunohistochemistry experiments revealing 

that several types of tumors express PD-L1. Dr. Wood provided Dr. Honjo with the first confirmation that the PD1/PD-L1 interaction was inhibitory, supported by experimental data. Drs. Freeman and Wood’s work on PD-L1, 

Dr. Wood’s discovery that the PD-1/PD-L1 interaction inhibits the immune response, and Dr. Freeman’s discovery 

of PD-L1 expression by human tumors were significant 

building blocks upon which the ’474 patent is built. 

ii. The remaining patents

Each of the remaining patents recites treatment of tumors, lung cancer, or melanoma by administering anti-PD1 or anti-PD-L1 antibodies. Ono makes arguments about 

the remaining patents, but each argument depends significantly on our acceptance of its arguments regarding the 

’474 patent. As we concluded above, discovery of PD-1 in a 

vacuum was insufficient for conception. 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. 

Ultimately, the decision in this appeal rests on the extensive factual determinations made by the district court 

relating to the work performed together by Drs. Wood and 

Freeman, and Dr. Honjo that were not clearly erroneous, 

and the court made no errors of law. 

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CONCLUSION

We have considered the parties’ remaining arguments 

but find them unpersuasive. Because we conclude that the 

district court did not err in holding Drs. Freeman and Wood 

should be included as joint inventors of the ’048, ’179, ’474, 

’999, ’994, and ’899 patents, we affirm the district court’s 

conclusions.

AFFIRMED

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