Ajinomoto Co. Inc v. Int'l Trade Comm'n

• Decision Date: 08 March 2010
• Docket Number: No. 2009-1081.,2009-1081.
• Citation: 597 F.3d 1267
• Parties: AJINOMOTO CO., INC. and Ajinomoto Heartland LLC, Appellants, v. INTERNATIONAL TRADE COMMISSION, Appellee, and Global Bio-Chem Technology Group Company Limited, Changchun Dacheng Bio-Chem Engineering Development Co., Ltd., Changchun Bao-$$$ cheng Bio-Chem Development Co., Ltd., Changchun Dahe Bio Technology Development Co., Ltd., and BioChem Technology (HK) Limited, Intervenors.
• Court: U.S. Court of Appeals — Federal Circuit

597 F.3d 1267

AJINOMOTO CO., INC. and Ajinomoto Heartland LLC, Appellants, v. INTERNATIONAL TRADE COMMISSION, Appellee, and Global Bio-Chem Technology Group Company Limited, Changchun Dacheng Bio-Chem Engineering Development Co., Ltd., Changchun Bao-$$$ cheng Bio-Chem Development Co., Ltd., Changchun Dahe Bio Technology Development Co., Ltd., and BioChem Technology (HK) Limited, Intervenors.

No. 2009-1081.

United States Court of Appeals, Federal Circuit.

March 8, 2010.

Editor's Note: The opinion of the United States Court of Appeals, Federal Circuit, in TiVo Inc. v. EchoStar Corporation, published in the advance sheet at this citation, 597 F.3d 1247 was withdrawn from the bound volume because it was vacated on grant of rehearing en banc. For order vacating opinion, see 2010 WL 1948577.

COPYRIGHT MATERIAL OMITTED

Joseph M. Malkin, Orriek, Herrington &amp Sutcliffe LLP, of San Francisco, CA, argued for appellants. Of counsel were E Joshua Rosenkranz and Alex V. Chachkes of New York, NY, and Kurt T. Mulville, of Irvine, CA.

James A. Worth, Attorney, Office of the General Counsel, United States International Trade Commission, of Washington, DC, argued for appellee. With him on the brief were James M. Lyons, General Counsel, and Wayne W. Herrington, Assistant General Counsel.

Claire Laporte, Foley Hoag LLP, of Boston, MA, argued for intervenors. With her on the brief were DeAnn F. Smith, Jeremy A. Younkin, and Marco J. Quina. Of counsel on the brief were Ruixue Ran, East Associates Law Firm, of Beijing, China, and Tom M. Schaumberg and Sarah E. Hamblin, Adduci, Mastriani & Schaumberg LLP, of Washington, DC.

Before NEWMAN, LOURIE and LINN, Circuit Judges.

LOURIE, Circuit Judge.

Ajinomoto Co., Inc. and Ajinomoto Heartland LLC (collectively, "Ajinomoto") appeal from the final determination of the International Trade Commission ("Commission") that the importation and sale of certain lysine feed products did not violate section 337 of the Tariff Act of 1930 as amended, 19 U.S.C. § 1337. The Commission found that (1) the asserted claims of Ajinomoto's U.S. Patents 5, 827, 698 ("the '698 patent") and 6, 040, 160 ("the '160 patent") are invalid under 35 U.S.C. § 112 for failure to comply with the best mode requirement and (2) the '698 patent is unenforceable due to inequitable conduct. We affirm.

BACKGROUND

I.

The '698 and '160 patents relate to improved methods of producing L-lysine ("lysine") by cultivating Escherichia bacteria that have been genetically engineered to produce and accumulate greater quantities of lysine than naturally occurring (or wildtype) bacterial strains. Lysine is an essential amino acid, which means that most animals cannot synthesize it but must obtain it directly from their diets. Consequently, feed producers and farmers regularly add lysine as a necessary dietary supplement to low-protein grass feed for livestock. To supply this billion dollar worldwide market for lysine, the industry employs microorganisms such as Escherichia coli ("E. coli") that can synthesize lysine from a carbon source (e.g., a sugar such as glucose) through a well-known biosynthetic pathway.

In nature, E. coli produce and accumulate only small amounts of lysine for their own nutrition. This low-level production limits the amount of lysine that can be collected from its cultivation. The patents involved in this case alter two mechanisms that contribute to E. coli's limited lysine production. The first mechanism, known as "feedback inhibition, " is triggered bylysine itself. Specifically, when sufficient lysine is present to meet the organism's needs, lysine inhibits its own production by inhibiting the activity of certain of its biosynthetic enzymes. At the same time, E coli also employ enzymes, called lysine decarboxylases, which break down any extra lysine produced into a non-nutritious byproduct. Both mechanisms—feedback inhibition and lysine degradation—keep E. coli from accumulating excess lysine.

Scientists at Ajinomoto disrupted the lysine degradation limitation imposed on lysine production by engineering an E. coli with a mutant lysine decarboxylase gene. Specifically, the '698 patent, entitled "Lysine Decarboxylase Gene and Method of Producing L-Lysine, " discloses the identification of the lysine decarboxylase gene Idc and the creation of an E. coli strain with mutations in Idc that reduce or eliminate lysine decarboxlyase activity. Asserted claim 15 of the '698 patent covers a method of producing lysine by cultivating E. coli with mutant Idc and collecting the accumulated lysine. The asserted claim, rewritten to include the claims from which it depends, reads as follows:

15. A method for producing L-lysine, comprising:

(a) cultivating an isolated microorganism belonging to the genus Escherichia, wherein the microorganism contains a [mutant lysine decarboxylase] in a liquid medium, thereby producing the L-lysine and accumulating the L-lysine in the liquid medium, and

(b) collecting the L-lysine produced and accumulated in step (a), wherein the microorganism belongs to the species Escherichia coli.

The '698 patent claims priority from a Japanese application filed on December 9, 1994, and issued on October 27, 1998.

Scientists at Ajinomoto similarly affected the feedback inhibition limitation im posed on lysine production by engineering an E. coli with a mutant lysine biosynthetic enzyme. Specifically, the '160 patent, entitled "Method of Producing L-Lysine by Fermentation, " discloses the creation of an E. coli strain with at least one of two mutations in dapA, the gene encoding the biosynthetic enzyme dihydrodipicolinate synthase ("DDPS"). The mutations release DDPS from the feedback inhibition imposed by excess lysine, and result in an E. coli strain that produces greater amounts of lysine than wild-type strains. Asserted claim 15 of the '160 patent covers a method of producing lysine by cultivating E. coli that contain mutant dapA and collecting the accumulated lysine. The asserted claim, rewritten to include the claim from which it depends, reads as follows:

15. A method of producing L-lysine, comprising: cultivating a bacterium belonging [to] the genus Escherichia which is transformed with a DNA coding for a dihydrodipicolinate synthase originating from a bacterium belonging to the genus Escherichia and having mutation to desensitize feedback inhibition of L-lysine, wherein the mutation is selected from the group consisting of [a mutation to replace the alanine residue at the 81st position and/or a mutation to replace the histidine residue at the 118th position] in a suitable culture medium, producing and accumulating L-lysine in the culture thereof, and collecting L-lysine from the culture.

The '160 patent was originally filed in Japan on December 8, 1993, and subsequently filed in the United States through the Patent Cooperation Treaty ("PCT") on November 28, 1994. It entered the national phase in the United States on June 9, 1997, and issued as the '160 patent on March 21, 2000.

Both patents disclose certain E. coli host strains for practicing the claimed inven-tions. Specifically, the '698 patent describes a two-step process of producing a mutant Idc host strain. '698 patent, col.8 1. 40-col.9 1.42. The first step subjects a wild-type E. coli strain, W3110, to NTG mutation/AEC selection to identify a strain having lysine productivity. Id. col.8 11.4063; see also col.5 11.20-43. The specification identifies that strain as WC196 and indicates that the inventors deposited WC196 in an international depository. Id. col.8. 11. 57-63; see also col.5 11.34^3. In the second step the mutant Idc gene is inserted into the WC196 strain to create the Idc mutant strain, identified as WC196L. Id. col.9 11.23-42. In contrast to the disclosure in the specification, it is undisputed that the actual strain used by the inventors had two additional genetic alterations made to it before the addition of mutant Idc. Specifically, the inventors first modified the wild-type W3110 strain to insert a variant lysC, a gene encoding an enzyme in the lysine biosynthesis pathway. The inventors identified this strain as WC80. Then, following the NTG mutation/AEC selection step, which resulted in the strain WC80196, the inventors inserted sucrose utilization genes into the E. coli to permit the resulting strain to use sucrose as a carbon source. The inventors identified this host strain as WC80-196S. Only then did the inventors insert the Idc mutation into the WC80-196S host strain.

Similarly, the '160 patent discloses two host strains, B-399 and W3110(tyrA), into which the inventors introduced mutant dapA. '160 patent, col.27 11.10-11, col.29 1.43. Yet, before filing the Japanese application from which the '160 patent claims priority, the inventors characterized a different strain, AE-70, as their best lysine producer.

II.

On April 25, 2006, Ajinomoto filed a complaint at the Commission alleging a violation of section 337 in the importation and sale of certain lysine feed products made by the methods claimed in the '698 and '160 patents. The complaint named Global BioChem Technology Group Company Limited; Changchun Dacheng BioChem Engineering Development Co., Ltd. Changchun Baocheng Bio-Chem Development Co., Ltd.; Changchun Dahe Bio Technology Development Co., Ltd.; and Bio-Chem Technology (HK) Limited (collectively, "GBT") as respondents. On May 24, 2006, the Commission initiated an investigation based on Ajinomoto's complaint. 71 Fed.Reg. 30, 958 (May 31, 2006). Before trial, GBT admitted infringement of both patents with regard to the importation and sale of lysine made by a certain bacterial strain.

On July 31, 2008, the Administrative Law Judge ("ALJ") rendered his initial determination, finding no violation of section 337. Specifically, the ALJ found that the asserted claims were invalid for multiple violations of the best mode requirement of 35 U.S.C. § 112, first paragraph and that both patents were unenforceable for inequitable...