Amgen Inc. v. Hoechst Marion Roussel, Inc.

• Decision Date: 06 January 2003
• Docket Number: No. 01-1191.,No. 01-1218.,01-1191.,01-1218.
• Parties: AMGEN INC., Plaintiff-Cross Appellant, v. HOECHST MARION ROUSSEL, INC. (now known as Aventis Pharmaceuticals, Inc.) and Transkaryotic Therapies, Inc., Defendants-Appellants.
• Court: U.S. Court of Appeals — Federal Circuit

314 F.3d 1313

AMGEN INC., Plaintiff-Cross Appellant, v. HOECHST MARION ROUSSEL, INC. (now known as Aventis Pharmaceuticals, Inc.) and Transkaryotic Therapies, Inc., Defendants-Appellants.

No. 01-1191.

No. 01-1218.

United States Court of Appeals, Federal Circuit.

Decided: January 6, 2003.

Rehearing and Rehearing En Banc Denied: March 3, 2003.

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Lloyd R. Day, Jr., Day, Casebeer, Madrid & Batchelder, LLP, of Cupertino, CA, argued for plaintiff-cross appellant. Of counsel on the brief were Edward M. O'Toole, Howrey, Simon, Arnold & White, of Chicago, IL; Stuart L. Watt, Amgen Inc., of Thousand Oaks, CA; and D. Dennis Allegretti, Duane, Morris & Heckscher, LLP, of Boston, MA. Of counsel were Wendy A. Whiteford, Steven M. Odre, Monique L. Cordray, Robert R. Cook, Amgen Inc., of Thousand Oaks, CA. Of counsel were David M. Madrid, Robert M. Galvin, Terry L. Tang, Paul S. Grewal, Richard C. Lin, Jonathan Loeb, Jackie N. Nakamura, and Matthew E. Hocker, Day, Casebeer, Madrid & Batchelder, LLP, of Cupertino, CA; and Richard M. Wong, Duane, Morris & Heckscher, LLP, of Boston, MA.

Herbert F. Schwartz, Fish & Neave, of New York, NY, argued for defendants-appellants. With him on the brief were Kenneth B. Herman, James F. Haley, Jr., Denise L. Loring, Douglas J. Gilbert, Frances M. Lynch, Gerald J. Flattmann, Jr., and Robert B. Wilson. Of counsel on the brief were Robert S. Frank, Jr. and Eric J. Marandett, Choate, Hall & Stewart, of Boston, MA. Also of counsel on the brief were Michael J. Astrue and Mary S. Consalvi, Transkaryotic Therapies, Inc., of Cambridge, MA.

Before MICHEL, CLEVENGER, and SCHALL, Circuit Judges.

MICHEL, Circuit Judge.

Plaintiff-Cross Appellant Amgen Inc. ("Amgen") is the owner of numerous patents directed to the production of erythropoietin ("EPO"), a naturally occurring hormone that controls the formation of red blood cells in bone marrow. Amgen markets and sells EPOGEN®, a highly successful commercial embodiment of the patented erythropoietin. Seeking to impede defendants-appellants Hoechst Marion Roussel, Inc. and Transkaryotic Therapies, Inc. (collectively "TKT") from commercializing a competitive EPO product, Amgen filed a declaratory judgment action in the United States District Court for the District of Massachusetts in April 1997, alleging that TKT's Investigational New Drug Application ("INDA") infringed United States Patent Nos. 5,547,933 ("the '933 patent"); 5,618,698 ("the '698 patent"); and 5,621,080 ("the '080 patent"). The complaint was amended in October 1999 to include United States Patent Nos. 5,756,349 ("the '349 patent") and 5,955,422 ("the '422 patent"), which issued after suit was filed.

After a three-day Markman hearing, the case was tried to the court for 23 days over the course of four months. In January 2001, the district court issued an exhaustive 244-page opinion in which it: (i) construed the disputed claims; (ii) held each of the patents enforceable; (iii) held the '080, '349 (product claims), and '422 patents valid and infringed; (iv) held the '698 patent not infringed; and (v) held the '933 patent not infringed or, in the alternative, invalid for failure to satisfy 35 U.S.C. § 112. Amgen, Inc. v. Hoechst Marion Roussel, Inc., 126 F.Supp.2d 69, 57 USPQ2d 1449 (D.Mass.2001). On appeal, TKT urges reversal on the grounds that the patents in suit are all unenforceable, that the district court's claim construction was erroneous, and alternatively, if that claim construction was correct, that the court's validity determinations were erroneous. Amgen asserts, in its cross appeal, that the district court committed error: (i) by comparing the accused process to the examples in the specification rather than the limitations of the method claims of the '349 and '698 patents; and (ii) by holding the '933 patent invalid for failure to comply with § 112. We heard oral argument on May 7, 2002.

We commend the district court for its thorough, careful, and precise work on what is indubitably a legally difficult and technologically complex case. There is no doubt that the court marshaled tremendous time and resources in its effort to reach correct results. Nevertheless, because we must conclude that the court committed certain errors of law in certain of its validity and infringement determinations, we cannot affirm the judgment in its entirety.

We affirm in toto the district court's claim construction. We also affirm: (i) its determination that none of the patents in suit is unenforceable for inequitable conduct; (ii) its contingent determination that the '933 patent is invalid under § 112 ¶ 1; (iii) its grant of summary judgment of infringement of '422 patent claim 1; (iv) its determination that the '080, '933, '349, and '698 patents are not anticipated by the Sugimoto reference; and (v) its determination that '349 patent claims 1, 3-4, and 6 are infringed. Because the district court misapplied the law, however, we vacate: (i) its determination that the '933 patent is not infringed; (ii) its determination that the '080 patent is infringed under the doctrine of equivalents; (iii) its determination that the '080, '349, and '422 patents are not invalid; and (iv) its determination that the asserted method claims of the '698 patent and '349 patent claim 7 are not infringed. Accordingly, we remand for the district court to reconsider: (i) whether the '080, '349, and '422 patents are obvious in light of the Sugimoto prior art or anticipated or obvious in light of the Goldwasser prior art; (ii) whether the '422 patent is anticipated by Sugimoto reference (and whether Amgen can prove its nonenablement); (iii) whether the asserted claims of the '698 patent and '349 patent claim 7 are infringed by the accused method; and (iii) whether the '080 patent is infringed under the doctrine of equivalents. In sum, as further explained in detail below, we affirm in part, vacate in part, and remand for further proceedings consistent herewith.

BACKGROUND

As the district court set out in painstaking detail the basics of the underlying technology, we will provide only a brief summary here. The reader's familiarity with the fundamentals of molecular biology, genetics, and recombinant DNA technology necessary to this appeal is presumed.¹

EPO is a naturally occurring protein that initiates and controls erythropoiesis, the production of red blood cells in bone marrow. Red blood cells are critical because they contain hemoglobin, a protein responsible for transporting oxygen from the lungs to peripheral tissues. Because EPO is produced in the kidney, patients with chronic kidney (renal) failure lack normal levels of EPO and, as a result, have a sub-optimal number of red blood cells — a condition called anemia. The therapeutic goal for treating anemic patients is to increase the "hematocrit level," which represents the ratio of red blood cells to total blood volume, to normal or near-normal levels. This is accomplished through the introduction of additional EPO into the patient's system.

The implementation of this seemingly simple solution, introduction of exogenous EPO, proved to be difficult. Because human EPO is produced in very small amounts (even from the healthy human kidney), it is difficult to obtain by conventional methods. Early attempts to recover EPO from plasma or from human urine ("urinary EPO" or "uEPO") were unsuccessful because such recovery employed techniques that were complicated, yet still resulted in a low-yield, high-impurity, or unstable EPO end product. '933 patent, col. 6, line 60 — col. 7, line 42. Similar attempts using antibody techniques failed because of difficulty in providing for the large-scale isolation of quantities of EPO from mammalian sources sufficient for further analysis, clinical testing, or therapeutic use. Id., col. 9, lines 2-8. The first successful method of production of a therapeutically effective amount of erythropoietin used recombinant EPO ("rEPO") techniques; Amgen is recognized as the pioneer. See, e.g., Molecular Biology and Biotechnology at 108.

Amgen scientist Dr. Fu-Kuen Lin is the named inventor on all five patents in suit. Instead of attempting to purify EPO from natural sources, Lin isolated and characterized monkey and human EPO genes, then used conventional recombinant DNA technology to produce large amounts of rEPO. '933 patent, col. 13, lines 50-53. Lin was able to determine the entire DNA sequence of human EPO and from that, its predicted amino acid sequence. Id., Fig. 6; col. 10, lines 65 — col. 11, line 2. Using the isolated human EPO gene, Lin described several methods for producing therapeutically effective amounts of human EPO using an expression vector.² Id., col. 21, line 42—col. 25, line 27.

EPOGEN®, the commercial embodiment of Amgen's patented EPO product, is produced by the method disclosed in patent specification Example 10. That example describes the production of human EPO through transfection (introduction) of exogenous DNA into host Chinese hamster ovary ("CHO") cells. The CHO host cell, using its own transcription machinery, then expresses human rEPO in abundance, which then accumulates in the host cell cytoplasm or in the culture media. Id., col. 37, lines 43-49. The rEPO so recovered has the same or similar amino acid sequences and biological properties as naturally occurring human EPO, but differs in its "glycosylation," i.e., in the patterns of branched carbohydrate chains that attach to the protein. '933 patent, col. 10, lines 34-41.

The patents in suit, which all claim priority to a December 1983 application long since abandoned, are continuations of a common ancestor — United States Patent No. 4,703,008 — which was at issue in this court's landmark decision in Amgen, Inc. v. Chugai Pharm. Co., 927 F.2d 1200, 18 USPQ2d 1016 (Fed.Cir.1991).³ The '933 patent issued on August 20,...