Bristol-Myers Squibb v. Rhone-Poulenc Rorer

• Citation: 326 F.3d 1226
• Decision Date: 15 April 2003
• Docket Number: No. 02-1280.,No. 02-1281.,02-1280.,02-1281.
• Parties: BRISTOL-MYERS SQUIBB COMPANY, Plaintiff-Appellee, v. RHONE-POULENC RORER, INC., Rhone-Poulenc Rorer, S.A., and Centre National de la Recherche Scientifique, Defendants-Appellants. Rhone-Poulenc Rorer, Inc. and Rhone-Poulenc Rorer, S.A., Plaintiffs/Counterclaim Defendants-Appellants, and Centre National de la Recherche Scientifique, Counterclaim Defendant-Appellant, v. Bristol-Myers Squibb Company, Defendant/Counterclaimant-Appellee.
• Court: U.S. Court of Appeals — Federal Circuit

326 F.3d 1226

BRISTOL-MYERS SQUIBB COMPANY, Plaintiff-Appellee, v. RHONE-POULENC RORER, INC., Rhone-Poulenc Rorer, S.A., and Centre National de la Recherche Scientifique, Defendants-Appellants.

Rhone-Poulenc Rorer, Inc. and Rhone-Poulenc Rorer, S.A., Plaintiffs/Counterclaim Defendants-Appellants, and Centre National de la Recherche Scientifique, Counterclaim Defendant-Appellant, v. Bristol-Myers Squibb Company, Defendant/Counterclaimant-Appellee.

No. 02-1280.

No. 02-1281.

United States Court of Appeals, Federal Circuit.

April 15, 2003.

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Robert L. Baechtold, Fitzpatrick, Cella, Harper & Scinto, of New York, NY, argued for plaintiff-appellee. With him on the brief were Thomas H. Beck, Dominick A. Conde, William E. Solander, and Sandy Choi.

Donald R. Dunner, Finnegan, Henderson, Farabow, Garrett & Dunner, L.L.P., of Washington, DC, argued for defendants-appellants. With him on the brief was Doris Johnson Hines. Of counsel on the brief was Ross J. Oehler, Aventis Pharmaceuticals Inc., of Bridgewater, NJ.

Before CLEVENGER, SCHALL, and PROST, Circuit Judges.

PROST, Circuit Judge.

Rhone-Poulenc Rorer Inc., Rhone-Poulenc Rorer, S.A., and Centre National De La Recherche Scientifique (collectively "RPR") appeal from the judgments of the United States District Court for the Southern District of New York: (1) holding that RPR obtained United States Patent No. 4,924,011 ("the '011 patent") and United States Patent RE 34,277 ("the '277 patent") by inequitable conduct and, thus, that its '277 patent is unenforceable; and (2) denying RPR's motion for summary judgment of infringement of claim 14 of the '277 patent under 35 U.S.C. § 271(f)(1) and (2). Bristol-Myers Squibb Co. v. Rhone-Poulenc Rorer, Inc., Nos. 95-CV-8833, 96-CV-2346, 98-CV-356, 2002 WL 59429 (S.D.N.Y. Jan. 16, 2002), 2001 WL 1263299 (S.D.N.Y. Oct.19, 2001). Because the district court's holding that RPR committed inequitable conduct is not an abuse of discretion, we affirm.

I

The patents at issue claim a semi-synthesis of taxol, a cancer chemotherapeutic agent. The inventors' method involves modifying 10-deacetylbaccatin III ("10-DAB") with an acetyl group and adding a (2R, 3S) 3-phenylisoserine side chain ("the side chain") through an esterification reaction. Several hydroxyl groups, located on both the 10-DAB and side chain molecules, readily react to form other unwanted products. To overcome this problem, the inventors devised a method of utilizing "protecting groups" to prevent particular hydroxyl groups on the 10-DAB core and side chain molecules from reacting in side reactions and thereby preventing the formation of taxol. First, starting with 10-DAB, a hydroxy-protecting group is introduced at the C-7 hydroxyl position on the 10-DAB molecule to form the C-7 protected intermediate. Second, an acetyl group replaces the hydrogen atom that is bonded to the oxygen atom at the C-10 position on the 10-DAB molecule, forming protected Bacacatin III. Third, the side chain is protected by a hydroxy-protecting group at its C-2' position and then esterified (or coupled) with the protected Baccatin III at its C-13 position. Lastly, the hydroxy-protecting groups at the C-7 position of the Bacacatin III core and the C-2' position of the side chain are deprotected (removed) to form taxol.¹ Of particular significance in this appeal is that the subject patents stemmed from a scientific article, written by the named inventors of the patents, entitled "A Highly Efficient, Practical Approach to Natural Taxol," which was eventually published in the Journal of the American Chemical Society ("the JACS article").²

On approximately November 3, 1987, the inventors submitted a draft of what became the published JACS article to Jacques Pilard, a patent agent in the employ of RPR in France. The draft JACS article, written in English, stated that the conversion of 10-DAB to taxol "could be successfully achieved only with specific protecting groups and under unique reaction conditions."³ (emphasis added). It also explained the limitations of several protecting groups as follows:

• "A methoxymethyl [("MOM")] protecting group at C-2' could not be removed following esterification" (footnote 16 of the JACS article).

• "The trimethylsilyl [("TMS")] group could also be selectively introduced at C-7, but it proved unstable to the subsequent esterification conditions" (footnote 13 of the JACS article).

• "The tert-butyldimethylsilyl [("TBDMS")] group could not be cleanly introduced" at C-7 (footnote 13 of the JACS article).

On approximately November 17, 1987, Mr. Pilard recommended to one of the inventors that the draft publication should or could be the subject of a patent application. In a letter sent to Mr. Pilard dated January 29, 1988, P.E. Simon of RPR's Grants and Licenses Department suggested that a patent application covering the inventors' semi-synthesis of taxol be filed in consideration of an exclusive license to RPR. On or about March 7, 1988, two of the inventors provided Mr. Pilard their resumes and an invention disclosure, entitled "Modes Operatoires," which described their semi-synthesis of taxol in detail. Consistent with the draft JACS article, the Modes Operatoires also explained the limitations of several protecting groups. Specifically, it stated the following:

• The regioselective protection of the hydroxyl at C-7 of 10-DAB was also obtained with TMS. "However, this [TMS] group proved too fragile in the esterifying reaction with the protected side chain."

• "The protecting reaction does not go forward with the [TBDM] chloride." (English translation of French original)

Moreover, the Modes Operatoires stated the hydroxyl function of the side chain was protected with a wide variety of protective groups, such as the MOM group, but it did not state that MOM could be removed.

On March 10, 1988, Mr. Pilard began drafting a French patent application for the semi-synthesis of taxol. In claim 1 of the draft patent application, Mr. Pilard claimed the process as one "in which R2 is a hydroxy-protecting group ... [and] in which R3 is a hydroxy-protecting group," without specifying any limitation as to the hydroxy-protecting groups that could be used in the process. In claim 2 of the draft application, Mr. Pilard claimed the process according to claim 1 "in which R2 is chosen from [MOM and other compounds]... and R3 is chosen from trialkylsilyl groups in which each alkyl portion contains one to three carbon atoms."⁴ (The '011 patent application is an English translation of the French application.) Not only did Mr. Pilard specify that MOM and TMS were permissible hydroxy-protecting groups in claim 2, but he also stated in the specification of the draft patent application that "R2 denotes, more especially, a [MOM and other compounds] ... radical" and that "[p]referably, R3 is a[TMS] ... radical."

On approximately March 18, 1988, Mr. Pilard sent his draft of the French patent application to two of the inventors asking them to carefully review it and add all the complements and modifications they deemed necessary. They made no substantive changes to either the specification or the claims. Mr. Pilard filed the French patent application on April 6, 1988. The Journal of the American Chemical Society received the draft article on April 20, 1988, and it was published on August 17, 1988.

In March 1989, Mr. Pilard sent a copy of the French application and a search report dated November 24, 1988, generated by the French National Institute of Industrial Property, to J.A. Kemp & Company for translation into English and forwarding to Mr. Ellsworth H. Mosher, RPR's United States patent attorney. The search report did not list the JACS article and Mr. Pilard did not send a copy of the JACS article, the Modes Operatoires, or any of the inventors' test results to J.A. Kemp & Company or Mr. Mosher.

On April 3, 1989, Mr. Mosher filed the '011 patent application with the United States Patent and Trademark Office ("PTO"). The filed patent application, except for the abstract, is an English translation of the French patent application previously prepared and filed by Mr. Pilard. Mr. Mosher, who never received a copy of the JACS article from Mr. Pilard, did not disclose it to the PTO.

At some point during the prosecution of the '011 patent, the Examiner assigned to the '011 patent application asked the PTO Scientific Library to perform a computer search of chemical abstracts using the chemical structure of claim 1 as the subject matter to be searched. The generated search report listed the JACS article as "Answer 1 of 11" and identified, among other attributes, its year of publication, 1988. The search report also listed another article, authored by two of the inventors of the '011 patent and published in 1987, as "Answer 5 of 11." The Examiner listed the 1987 article on a "Notice of References Cited" (Form PTO-892). However, the Examiner did not place his initials next to either of the listed articles on the search report. He placed the search report in the file history. On May 8, 1990, the PTO issued the '011 patent.

On approximately January 31, 1991, Mr. Pilard wrote to the European patent office and withdrew the claims previously drawn in the counterpart European patent application. He replaced those claims with a single claim (similar to claims 2-7 of the '011 patent) for the inventors' semi-synthesis process.

On June 11, 1991, Mr. Pilard sent Mr. Frederick F. Calvetti, a United States patent attorney in a different law firm than the one employing Mr. Mosher, a letter by fax and post about filing a reissue patent application with additional claims directed to the disclosed but unclaimed intermediates of formulas IV and V of the '011 patent.⁵ Mr. Pilard's letter attached a copy of the '011 patent and the JACS article with footnote 16 circled, although it is unclear who circled the footnote. On June 13, 1991, Mr. Calvetti...