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Plaintiff University Fails to Provide Clear and Convincing Evidence of Joint Inventorship Where the Parties’ Respective Stories Are “Equally Plausible”

April 09, 2010

Decision icon Decision

Last Month at the Federal Circuit - May 2010

Judges: Michel, Clevenger (author), Dyk (concurring-in-part and dissenting-in-part)

[Appealed from: D. Del., Judge Robinson]

In Vanderbilt University v. ICOS Corp., No. 09-1258 (Fed. Cir. Apr. 7, 2010), the Federal Circuit affirmed the district court’s judgment that Vanderbilt University (“Vanderbilt”) failed to prove that Vanderbilt scientists were joint inventors on U.S. Patent Nos. 5,859,006 (“the ’006 patent”) and 6,140,329 (“the ’329 patent”), which were assigned to ICOS Corporation (“ICOS”).   

The patents at issue are directed to compounds and methods for treating erectile dysfunction, including the compound tadalafil, the active ingredient in the drug Cialis®.  Tadalafil belongs to a group of compounds that inhibit PDE5, a phosphodiesterase enzyme found in smooth muscle cells that binds to and breaks down cGMP, a cyclic nucleotide found in smooth muscle tissue.  In normal function, cGMP binds with and activates a cGMP-dependent protein kinase, which results in relaxation and dilation of the smooth muscle cell.  PDE5 inhibitors bind to PDE5 and prevent it from binding with and breaking down cGMP. 

Vanderbilt scientists Jackie D. Corbin and Sharron H. Francis were among the first to discover PDE5 in the late 1970s.  In 1989, Glaxo Inc. (“Glaxo”) entered into a research agreement with Dr. Corbin to underwrite Vanderbilt’s research of cGMP analogs.  Under the agreement, Vanderbilt retained ownership of intellectual property, but Glaxo was granted a license agreement to any discoveries.  During the three years of the program, Drs. Corbin, Francis, and Sekhar R. Konjeti (collectively “the Vanderbilt scientists”) submitted numerous presentations and progress reports to Glaxo. 

In 1990, Dr. Corbin disclosed to Glaxo Group Limited (“Glaxo U.K.”) that the potency of cGMP analogs is enhanced by adding a phenyl ring at the 8-position.  In 1991, however, Glaxo encouraged the Vanderbilt scientists to shift their future focus from cGMP analogs to PDE5 inhibitors.  Subsequently, the Vanderbilt scientists applied the results of their cGMP analog research to synthesize a new PDE5 inhibitor.  The Vanderbilt scientists ultimately attached a phenyl ring to the 8-position of known PDE5 inhibitor, 3-isobutyl-1-methylxanthine (“IBMX”), as well as an electron-donating hydroxyl group at the 4-position of the phenyl ring.  The Vanderbilt scientists determined that those modifications of IBMX created a PDE5 inhibitor they thought was 160 times more potent in inhibiting PDE5 than the original IBMX molecule.  Dr. Corbin drafted a letter to Vanderbilt’s general counsel disclosing possible therapeutic uses for the new IBMX analogs, including the treatment of male impotence.

In January 1992, Dr. Corbin sent a second research proposal to Glaxo U.K. detailing the test results of the cGMP analogs developed under the original research agreement.  In the proposal, Dr. Corbin also described the Vanderbilt scientists’ potent IBMX analog.  Dr. Corbin also proposed a second research agreement to Glaxo for funding of the Vanderbilt scientists’ work on PDE5 inhibitors going forward.  Male impotence was listed as an area of interest, though Glaxo was not researching male impotence at the time.  In February 1992, Dr. Corbin sent a more detailed research proposal to Dr. Barry Ross of Glaxo U.K. that disclosed the exact design of the Vanderbilt IBMX analog.  The detailed research proposal also identified a table of other analogs that Vanderbilt proposed for further testing.  Many of the listed compounds contained what Vanderbilt referred to as the “Vanderbilt structural features” of Vanderbilt’s IBMX analog.

Following the Vanderbilt scientists’ disclosure of the Vanderbilt structural features to Glaxo, a Glaxo research facility in Les Ulis, France (“Glaxo France”), tested 26 compounds for PDE5 inhibition in March 1992, including a compound it designated GR35273x.  Then, in April 1992, Dr. Ross forwarded copies of Vanderbilt’s second proposal to six Glaxo scientists, including Dr. Richard Labaudiniere, the head of chemistry and leader of the PDE5 project at Glaxo France.  In turn, Glaxo France tested 29 compounds for PDE5 inhibition, including a beta-carboline compound designated GR30040x, which Dr. Labaudiniere identified as a lead compound for further research.  Dr. Labaudiniere assigned the further GR30040x research to Dr. Alain Claude-Marie Daugan, the named inventor on the patents at issue, as a separate study.  In the course of testing various modifications to the GR30040x compound between June 1992 and January 1994, Dr. Daugan discovered tadalafil.

In 1991, Glaxo assigned to ICOS the rights, title, and interest in the compounds covered by the ’006 and ’329 patents.  Vanderbilt brought this suit under 35 U.S.C. § 256 against ICOS to correct inventorship of the patents, asserting that the Vanderbilt scientists should be added as joint inventors.  According to Vanderbilt, the GR30040x compound could not have been identified by Dr. Labaudiniere as the lead compound without his use of the Vanderbilt structural features.  Nor could tadalafil have been identified by Dr. Daugan without his reliance on Vanderbilt’s work.  The district court held a bench trial and found in favor of ICOS.

On appeal, Vanderbilt raised two arguments.  First, Vanderbilt argued that its disclosure of the Vanderbilt structural features led to Glaxo France’s identification of the GR30040x.  In this regard, the gist of Vanderbilt’s case was that Dr. Labaudiniere could only have identified GR30040x by using the Vanderbilt structural features.  Second, Vanderbilt alleged that the key modification to GR30040x that yielded tadalafil was the addition of an electron-donating substituent on the phenyl ring based upon the work of the Vanderbilt scientists.

According to the Federal Circuit, a primary focus of 35 U.S.C. § 116, the applicable section for joint inventorship, has always been on collaboration and joint behavior.  The Court noted that the interplay between conception and collaboration requires that each coinventor engage with the other coinventors to contribute to a joint conception.

Vanderbilt attempted to piece together sufficient facts to demonstrate that the Vanderbilt structural features must have been used by Dr. Labaudiniere to identify GR30040x.  However, ICOS contended that Dr. Labaudiniere independently discovered the compounds to be tested for PDE5 inhibition through his knowledge of beta-carbolines and their vasorelaxation effect.  ICOS also pointed to testimony of Dr. Labaudiniere and Dr. Daugan to corroborate its theory on the identification of GR30040x.  Dr. Labaudiniere testified that he did not have any knowledge about the Vanderbilt scientists’ research until June 1993, he did not consider IBMX as a starting point for his work on PDE5 inhibitors, and he was not aware of anyone at Glaxo France using data relating to IBMX analogs or trying to develop PDE5 inhibitors that would resemble cGMP.  Dr. Daugan confirmed that his recollection matched that of Dr. Labaudiniere.  In sum, ICOS argued that Vanderbilt’s case failed for lack of evidence of any joint collaboration on the invention since neither of the Glaxo France scientists had any knowledge of the work of the Vanderbilt scientists when they did their work relating to the discovery of tadalafil.

Conversely, Vanderbilt instead proposed that Dr. Labaudiniere reviewed the Vanderbilt scientists’ second research proposal and conducted a substructure search based upon the Vanderbilt IBMX analog.  Vanderbilt pointed out that just weeks after receiving Vanderbilt’s proposal, Glaxo France tested 29 compounds for PDE5 inhibition.  Vanderbilt pointed out a number of structural similarities between the tested compounds and its February research proposal.

Vanderbilt’s second argument was that after the GR30040x project was assigned to Dr. Daugan, he added to tadalafil an additional element of the Vanderbilt structural features.  Vanderbilt argued that this modification directly used the results of the Vanderbilt scientists’ research.  ICOS responded that the modifications were all part of a standard trial and error procedure that would be tried with any molecules of interest.

The only evidence of record regarding Glaxo’s modifications to GR30040x was the testimony of Drs. Daugan and Labaudiniere.  Dr. Daugan testified that “[t]he first thing [he] did in this series was explore the replacement of the pyridinyl[] moiety with other heterocyclic or aromatic moieties.”  Slip op. at 13 (alterations in original).  Dr. Labaudiniere testified that there are a standard group of substitutions or additions that would be tried with any molecules of interest.  Dr. Labaudiniere characterized the modifications leading to tadalafil as “obvious” and conducted in a “trial-and-error” fashion.  Id.  There was no testimony or documentary evidence demonstrating a link between the Vanderbilt scientists and Dr. Daugan prior to the identification of tadalafil.  Indeed, Vanderbilt admitted in the district court that it had no direct evidence to support its view of the facts.

The Federal Circuit concluded that Vanderbilt failed to present clear and convincing evidence to support its argument that the work of the Vanderbilt scientists was appropriated by Dr. Labaudiniere for his substructure search.  With regard to Vanderbilt’s argument that Dr. Daugan made use of the Vanderbilt scientists’ research for the modifications to GR30040x, the Federal Circuit found that Vanderbilt also failed to present clear and convincing evidence to support its argument that the modifications to GR30040x by Dr. Daugan made use of the Vanderbilt scientists’ research. 

The Federal Circuit noted that the district court opinion contained some erroneous statements regarding the law of joint inventorship and a misunderstanding of the relevance of Board of Education ex rel. Board of Trustees of Florida State University v. American BioScience Inc., 333 F.3d 1330 (Fed. Cir. 2003).  The district court had relied on American BioScience to require that each coinventor should have an independent conception of the final compound for a chemical invention.  The district court ruled that because the Vanderbilt structural features constituted no more than a portion of a claimed compound, the Vanderbilt scientists cannot, as a matter of law, be joint inventors.  Although the Federal Circuit affirmed the district court’s final judgment, the Federal Circuit concluded that the district court’s interpretation of American BioScience was clearly wrong under its established precedent.  “Instead, a group of co-inventors must collaborate and work together to collectively have a definite and permanent idea of the complete invention.”  Slip op. at 19.  The Federal Circuit also stated that “[t]he determination of whether a person is a joint inventor is fact specific, and no bright-line standard will suffice in every case.”  Id. (quoting Fina Oil & Chem. Co. v. Ewen, 123 F.3d 1466, 1473 (Fed. Cir. 1997)).

The Federal Circuit concluded that the district court correctly noted that conception requires identification of the specific chemical structure of the compound.  The parties agreed that Dr. Daugan was the first to conceive of tadalafil.  The Federal Circuit also agreed with the district court’s finding that, after a careful review of the evidence, the parties’ respective stories about whether the Vanderbilt scientists contributed to the identification of GR30040x were  “equally plausible” and that Vanderbilt failed to produce any evidence of joint invention of tadalafil.  The Court held that the district court’s findings demonstrate that under the correct legal test, Vanderbilt did not carry its burden.  Accordingly, the Federal Circuit held that the district court’s erroneous interpretation of the Court’s case law was harmless error.

In a separate opinion concurring-in-part and dissenting-in-part, Judge Dyk agreed that the district court applied the wrong standard for joint inventorship.  But Judge Dyk disagreed from the majority’s conclusion that the district court’s legal error was harmless because, in his opinion, the findings were either contradictory or infected by the district court’s legal error.  Accordingly, Judge Dyk believed that the Court should vacate the judgment of the district court and remand so that the district court may make factual findings under the proper law.


Summary authored by Stephen C. Bellum, Ph.D., student associate at Finnegan.