## United States Court of Appeals for the Federal Circuit

2007-1266 CARNEGIE MELLON UNIVERSITY and THREE RIVERS BIOLOGICALS, INC., Plaintiffs-Appellants,

v. HOFFMANN-LA ROCHE INC., ROCHE MOLECULAR SYSTEMS, INC., ROCHE DIAGNOSTIC SYSTEMS, INC., ROCHE BIOMEDICAL LABORATORIES, INC., THE PERKIN-ELMER CORPORATION, and LABORATORY CORPORATION OF AMERICA HOLDINGS, Defendants-Appellees.

--------------------------------------------------------------- ------------- 2007-1267 CARNEGIE MELLON UNIVERSITY, Plaintiff-Appellant,

v. HOFFMANN-LA ROCHE INC., ROCHE MOLECULAR SYSTEMS, INC., ROCHE DIAGNOSTICS CORPORATION, LABORATORY CORPORATION OF AMERICA, and APPLERA CORPORATION, Defendants-Appellees. Frederick H. Colen , Reed Smith LLP, of Pittsburgh, Pennsylvania, argued for all plaintiffs-appellants. With him on t he briefs were Char les H. Dougherty, Jr. and Mark Levin

. Stephen S. Rabinowitz , Fried, Frank, Harris, Shri ver & Jacobson LLP, of New York, New York, argued for all defendants-appel lees. With him on the briefs were Mitchell Epner , Randy C. Eisensmith , and Alison R. Ladd

. Appealed from: United States District Cour t for the Northern District of California Judge Susan Illston

## United States Court of Appeals for the Federal Circuit

2007-1266 CARNEGIE MELLON UNIVERSITY and THREE RIVERS BIOLOGICALS, INC., Plaintiffs-Appellants,

v. HOFFMANN-LA ROCHE INC., ROCHE MOLECULAR SYSTEMS, INC., ROCHE DIAGNOSTIC SYSTEMS, INC., ROCHE BIOMEDICAL LABORATORIES, INC., THE PERKIN-ELMER CORPORATION, and LABORATORY CORPORATION OF AMERICA HOLDINGS, Defendants-Appellees.

------------------------------------------------------------------------------ 2007-1267 CARNEGIE MELLON UNIVERSITY, Plaintiff-Appellant,

v. HOFFMANN-LA ROCHE INC., ROCHE MOLECULAR SYSTEMS, INC., ROCHE DIAGNOSTICS CORPORATION, LABORATORY CORPORATION OF AMERICA, and APPLERA CORPORATION, Defendants-Appellees.

------------------------------------------------------------------------------ Appeal from the United States Distric t Court for the Northern District of California in Case Nos. 95- CV-3524 and 01-CV-0415, Judge Susan Illston._____________________ DECIDED: September 8, 2008

_____________________ Before LOURIE, BRYSON, and PROST, Circuit Judges

. LOURIE, Circuit Judge

. Carnegie Mellon University (“CMU”) and Three Rivers Biologicals, Inc. (collectively “appellants”) appeal from the decision of the Unit ed States District Court for the Northern District of Ca lifornia holding that Hoffmann-La Roche, Inc., Roche Molecular Systems, Inc., Roche Diagnosti c Systems, Inc., Roche Biomedical Laboratories, Inc., The Perkin Elmer Co rporation, and Laborator y Corporation of America Holdings (collectively “Roche”) do not infringe the patents in suit and that certain claims are invalid for lack of written description. Be cause we conclude that the district court did not err in holding the clai ms invalid for failure to meet the written description requirement, we affirm the court’ s judgment of invalidity. Because we conclude that the court did not err in its infringement analysis, we affirm the court’s judgment of noninfringement. BACKGROUND Proteins, one of the most versatile biomolecules, can serve many important roles, including as signal receptors, structur al elements, or enzymes . They are encoded by particular deoxyribonucleic acid (“DNA ”) sequences known as genes. The process by which cells use the information contained in genes to make corresponding proteins is referred to as expression. Expression involves two steps, viz. , transcription and translation. During transcription, the info rmation contained in a gene is copied into

2007-1266, -1267 2messenger ribonucleic acid (“mRNA”). The cell then assembles amino acids in the proper sequence during translation to make the protein based on the information contained in the mRNA. One gene in the bacterium E. coli , called the E. coli polA gene, encodes a protein known as E. coli DNA polymerase I. Since at least the 1970s, the E. coli polA gene has been the subject of scientific study. The wild-type E. coli polA gene consists of two parts—the structural gene (o r gene coding region) and a promoter, which is a DNA sequence that is involved in initiating tran scription. The expre ssion of a gene can be regulated through the use of a pr omoter by controlling the level of transcription. Some valuable proteins are ei ther difficult to purify from their natural sources or occur in minute quantities in nature. Thus , methods have been developed in the field of biotechnology “to synthesize useful quantities of specific proteins by controlling the mechanism by which living cells make proteins.” Carnegie Mellon Univ. v. Hoffmann-La Roche, Inc. , 55 F. Supp. 2d 1024, 1027 (N.D.Cal. 1999). One method involves introducing foreign genes into a bacterium, which can then replicate as the bacterium grows and divides. Such a method involves several steps, including isolating and cloning the gene that encodes the protein of interest and introducing the cloned gene into the host bacterium. The latter is accomplished by incorporating the gene into a cloning vector . Certain types of vectors include bacteriophages and plasmids, which are “small circ ular loop[s] of DNA found in bacteria, separate from the chromosome, that replicate[] like a chromosome.” Id. Recombinant DNA techniques are used to modify plasmi ds by recombining cloned genes and other

2007-1266, -1267 3segments of DNA that contain control sequences. The plasmid is then introduced into the host bacterium where it will replicat e as the bacterium grows and divides. The patents in suit, viz. , U.S. Patents 4,767,708 (“t he ’708 patent”), 5,126,270 (“the ’270 patent”), and 6,017,745 (“the ’745 patent ”) relate to “novel recombinant plasmids for the enhanced expression of an en zyme, to the preparation by gene cloning of such plasmids, to bacterial strains containing said plasmids, [and] to methods for the conditional control of the expression of said enzyme.” 1 ’708 patent col.1 ll.7-16. The patents teach that the enzyme of intere st is DNA polymerase I (Pol I), which, as discussed above, is encoded by the structural gene known as polA

. Id. col.1 ll.14- 15. In the prior art, scientists encountered difficulties cloning polA into multicopy plasmids because the increase in expressi on of DNA polymerase I above the natural level of expression was found to be lethal to a host bacterium. Id. col.1 ll.14-18. The claimed inventions overcome that problem by constructing a novel plasmid containing “the entire and undamaged polA gene coding region enzymatica lly excised from a DNA molecule,” which “contains essentially none of or at the most onl y a portion of the activity of its natural promoter.” Id . col.2 ll.23-29. The patents disclose that severely damaging the natural polA promoter sequence constituted a “significant discovery of the present invention since it e liminates or greatly reduces the unregulated expression of Pol I, which would otherwise be lethal to the cell.” Id. col.2 ll.43-46. By cloning the

1 The patents in suit, which are owned by CMU, all share a common specification. The ’708 paten t, which was filed by Edwin G. Minkley, Jr. and William E. Brown on August 7, 1984, issued from Application No. 07/638, 638 (“the ’638 application”). The ’270 patent is a continuation of the application that issued as the ’708 patent, and the ’745 patent is a continuation of the application that issued as the ’270 patent. Throughout this opinion, we will cite the ’708 patent when referencing the common specification. 2007-1266, -1267 4gene for DNA polymerase I into a vector along with a foreign pr omoter whose activity is conditionally controlled, one can obtain an amplified amount of DNA polymerase I. Throughout the specification, the patents teach that the host bacte rial strain that is used to achieve that objective is E. coli

. The patents in suit share a common specif ication, and the claims are directed to recombinant plasmids that contain gene c oding regions for the expression of DNA polymerase I from any bacterial source. Fo r example, claim 1 of the ’708 patent reads as follows: 1. A recombinant plasmid containing a cloned complete structural gene coding region isolated from a bacterial source for the expression of DNA polymerase I, under operable control of a conditionally controllable foreign promoter functionally linked to said structural gene coding region, said foreign promoter being functional to express said DNA polymerase I in a suitable bacterial or yeast host system. ’708 patent claim 1 (emphasis added). Cla im 1 of the ’270 patent recites: 1. A recombinant plasmid providing for Nick-translation activity isolated from a bacterial source , said plasmid capable of being placed in a bacterial host system such that the host system can grow and divide. ’270 patent claim 1 (emphasis added). Simila rly, claim 1 of the ’745 patent reads: 1. A recombinant plasmid contai ning a DNA coding sequence for the expression of DNA polymerase acti vity, wherein said DNA coding sequence is derived from a source that encodes a bacterial DNA Polymerase , said source not containing an amber mutation affecting expression of said DNA polymerase acti vity, such that when said plasmid is transformed into a bacterial host system the host system can grow and divide thereby replicating said plasmid. ’745 claim 1 (emphasis added). Roche commercially manufactures recombinant DNA polymerases. The accused product at issue in this appeal involv es a recombinant plasmid referred to as pLSG5, which causes host cells to express an enzyme known as Thermus aquaticus
2007-1266, -1267 5(“ Taq ”) DNA polymerase. On August 30, 1994, appellants filed suit against Roche asserting that its product, pLSG5, infringes the ’708 and ’270 patents. 2 The district court held a claim construction heari ng on January 14, 1997 and issued its claim construction ruling on March 31, 1997. The court construed the term “DNA polymerase” as requiring 3’-5’ exonuclease activity. Carnegie Mellon Univ. v. Hoffmann-La Roche Inc. , No. C 95-3524 SI, 1997 WL 33152823, at *8-*10 (N.D. Cal. Mar. 31, 1997). Roche filed separate motions for summary judgment seeking judgment that: 1) claims 1-19, 22- 40, and 43-45 of the ’708 patent were invalid for lack of written description under our holding in Regents of University of Ca lifornia v. Eli Lilly & Co. , 119 F.3d 1559 (Fed. Cir. 1997); 2) claims 1-6, 10-19, and 22-40 of the ’708 patent were not infringed; and 3) claims 1-2, 11-12, 14-15, 17-18, 20-21, 23-24, 26-27, 29-30, and 32-36 of the ’270 patent were invalid for lack of wri tten description under our holding in Gentry Gallery, Inc. v. Berkline Corp. , 134 F.3d 1473 (Fed. Cir. 1998), or, in the alternative, under Eli Lilly

. On May 12, 1999, the district cour t granted Roche’s motion for summary judgment of noninfringement. Carnegie Mellon Univ. v. Hoffmann-La Roche, Inc. , 55 F. Supp. 2d 1024 (N.D.Cal. 1999). In doing so, the district court concluded that there was no genuine issue of material fact as to whether the enzyme in the accused product possessed 3’-5’ exonuclease activity. Becaus e the undisputed eviden ce indicated that the accused products lacked that element, the court concluded that summary judgment of noninfringement of the ’708 patent was required.

2 In its original complaint, appellant s asserted that several of Roche’s recombinant DNA plasmids infringe the ’708 and ’270 patents. On appeal, however, appellants only challenge the district c ourt’s grant of summary judgment of noninfringement with respect to the pLSG5 plasmid. 2007-1266, -1267 6On August 19, 1999, the district cour t granted Roche’s motion for summary judgment of invalidity as to the ’270 patent. Carnegie Mellon Univ. v. Hoffmann-La Roche Inc. , No. C 95-3524 SI, 1999 WL 33298545 (N.D. Cal. Aug. 19, 1999). The court determined that the specif ication of the ’270 patent m ade clear that lethality was an essential feature of t he invention and thus, under Gentry Gallery , the claims of the patent must contain that f eature in order to comply with the written description requirement. Because the claims omit the f eature of lethality, t he court concluded that those claims of the ’270 patent were invalid. On June 27, 2001, relying on Eli Lilly , the district court granted Roche’s motion for summary judgment of invalidit y with regard to the ’708 patent. Carnegie Mellon Univ. v. Hoffmann-La Roche, Inc. , 148 F. Supp. 2d 1004 (N.D. Cal. 2001). The court concluded that while the claims of the ’708 patent claim recombinant plasmids “containing a cloned complete structural gene coding region from [any] bacterial sources for the expression of DNA polymer ase I,” the ’638 application only described recombinant plasmids containing the encoding gene region for E. coli DNA polymerase I and thus failed to adequately support the generic claims of the ’708 patent. On January 24, 2001, CMU initiated a sec ond patent infringement action against Roche, alleging that Roche infringed t he ’745 patent. Roche moved for summary judgment that claims 1-3, 12-14, 23-28, and 30-33 were invalid under the written description requirement of 35 U. S.C. § 112. On September 29, 2003, the district court granted that motion. Carnegie Mellon Univ. v. Hoffmann-La Roche, Inc. , No. C 01-0415 SI (N.D. Cal. Sept. 29, 2003). Again relying on Eli Lilly , the court determined that there was no genuine issue of material fact with regard to whether the ’745 patent complies

2007-1266, -1267 7with the written description requirement under 35 U.S.C. § 112 and granted Roche’s motion. Roche also moved for summary j udgment of noninfringement of claims 4-11, 15-22, and 29 of the ’ 745 patent under the doctrine of equivalents, and on February 26, 2004, the court grant ed that motion. Carnegie Mellon Univ. v. Hoffmann-La Roche, Inc. , No. C 01-0415 SI (N.D. Cal. Feb. 26, 2004). Roche additionally asserted that the patents were unenforceable based on inequitable conduct committed by appellants dur ing the prosecution of each of the asserted patents. The district court held a bench trial on that iss ue from August 1 to August 5, 2005. On March 22, 2007, the court issued its ruling, holding that Roche failed to present clear and convincing evi dence that appellants committed inequitable conduct. Carnegie Mellon Univ. v. Hoffmann-La Roche, Inc. , No. C 01-0415 SI, 2007 WL 902548 (N.D. Cal. Mar. 22, 2007). As su ch, the court concluded that none of the patents was unenforceable. On May 14, 2007, the district court enter ed final judgment in favor of Roche. Appellants timely appealed the di strict court’s grant of su mmary judgment with regard to noninfringement and invalidity. We have jurisdic tion pursuant to 28 U.S.C. § 1295(a)(1). DISCUSSION On appeal, appellants challenge the district court’s grant of summary judgment of invalidity with regard to claims 1-19, 22-40, and 43-45 of the ’708 pat ent, claims 1-2, 11- 12, 14-15, 17-18, 20-21, 23-24, 26-27, 29-30, and 32-36 of the ’270 patent, and claims 3, 14, 23-28, and 30-32 of the ’745 patent. In addition, appellants challenge the court’s grant of summary judgment of noninfringement of the assert ed claims of the ’708 patent and claims 4, 5, and 7 of the ’745 patent. Wh ile the decisions of the district court

2007-1266, -1267 8regarding the ’708, ’270, and ’745 patents were rendered in separate opinions and judgments, the appeals were cons olidated for argument in this court and we decide all of them together. We first consider appellant s’ arguments relating to validity. A. Standard of Review We review the district cour t’s grant of summary judgment de novo , reapplying the standard applicable at the district court. See Rodime PLC v. Seagate Tech., Inc. , 174 F.3d 1294, 1301 (Fed. Cir. 1999). Summary judgm ent is appropriate “if the pleadings, depositions, answers to interrogatories, and admissions on file , together with the affidavits, if any, show that there is no genuine issue as to any material fact and that the moving party is entitled to j udgment as a matter of law.” Fed. R. Civ. P. 56(c). In addition, in deciding a motion for summary judgment, “[t]he evidence of the nonmovant is to be believed, and all justifiable infe rences are to be drawn in his favor.” Anderson v. Liberty Lobby, Inc. , 477 U.S. 242, 255 (1986).
B. Written Description Section 112, paragraph 1 of t he Patent Act sets forth the written description requirement as follows: The specification shall contain a written de scription of the invention , and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enabl e any person skilled in the art to which it pertains, or wit h which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention. 35 U.S.C. § 112, ¶ 1 (emphasis added). T hus, paragraph 1 of § 112 requires a written description of the invention—a requirement separate and distinct from the enablement requirement. Vas-Cath Inc. v. Mahurkar , 935 F.2d 1555, 1563 (Fed. Cir. 1991); see Festo Corp. v. Shoketsu Kinz oku Kogyo Kabushiki Co., Ltd. , 535 U.S. 722, 736 (2002)
2007-1266, -1267 9(noting that “a number of statutory requirements must be satisfied before a patent can issue” including that the patent application “ describe , enable, and set forth the best mode of carrying out the invention”) (emphasis added); see also In re Curtis , 354 F.3d 1347, 1357 (Fed. Cir. 2004) (“We in terpret 35 U.S.C. § 112, ¶ 1 to require a written description requirement separate and apart from the enablement requirement.”); In re Ruschig , 379 F.2d 990 (C.C.P.A. 1967) (holding that the written description requirement is a requirement separate from enablem ent under 35 U.S.C. § 112, paragraph 1). The basic function of a patent specificat ion is to disclose an invention. It has long been the case that a pat entee “can lawfully claim only what he has invented and described, and if he claims more his patent is void.” O’Reilly v. Morse , 56 U.S. (15 How.) 62, 121 (1853). The written description serves a quid pro quo function “in which the public is given ‘meaningful disclosur e in exchange for being excluded from practicing the invention for a limited period of time.’” Univ. of Rochester v. G.D. Searle & Co., Inc. , 358 F.3d 916, 922 (Fed. Cir. 2004) (quoting Enzo Biochem, Inc. v. GenProbe Inc. , 323 F.3d 956, 970 (Fed. Cir. 2002)). To satisfy the written description requirement, “the applicant does not have to ut ilize any particular form of disclosure to describe the subject matter claimed, but the description must clearly allow persons of ordinary skill in the art to recognize that he or she invented what is claimed.” In re Alton , 76 F.3d 1168, 1172 (Fed. Cir. 1996) (citing In re Gosteli , 872 F.2d 1008, 1012 (Fed. Cir. 1989)) (quotations omitted). In ot her words, the applicant must “convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention,” Vas-Cath Inc. , 935 F.2d at 1563-64, and demonstrate that by disclosure in the specification of the patent. Whether the written

2007-1266, -1267 10description requirement is satisfied is a fact-based inquiry that will depend on the nature of the claimed invention, Enzo , 323 F.3d at 963, and the knowledge of one skilled in the art at the time an invention is made and a pat ent application is fil ed. Such knowledge may change as time progresses. See In re Wallach , 378 F.3d 1330, 1334 (Fed. Cir. 2004) (discussing how it is now a “routine matter” to convert between an amino acid sequence and the DNA sequences that can encode it such that an applicant need not specify each possible permutation of nucleic acid sequences for a particular protein). Our case law has examined compliance with the written description requirement in the context of biotechnologica l inventions in the past. In Regents of University of California v. Eli Lilly & Co. , 119 F.3d 1559 (Fed. Cir. 1997), we held, inter alia , that generic claims directed to recombinant pr okaryotic microorganisms comprising any vertebrate and mammalian cDNA were not adequately supported by the specification that only disclosed rat insulin cDNA. Id. at 1568. We stated t hat “[a]n adequate written description of a DNA, such as the cDNA of the recombinant plasmids and microorganisms of the claimed invention, requires a precise definition, such as by structure, formula, chemical name, or physi cal properties, not a mere wish or plan for obtaining the claimed c hemical invention.” Id. at 1566 (internal quotations omitted). We further held that “[a] descr iption of a genus of cDNAs may be achieved by means of a recitation of a representative number of c DNAs, defined by nucleotide sequence, falling within the scope of the genus or of a recitation of structur al features common to the members of the genus, which features constitu te a substantial porti on of the genus.” Id. at 1569.
1. The ’708 and ’745 Patents

2007-1266, -1267 11Appellants challenge the district court’s conclusion that certain claims of the ’708 and ’745 patents are invalid under § 112 in light of our holding in Eli Lilly . According to appellants, Eli Lilly is distinguishable from the present case because the invention in Eli Lilly was tied to a specific cDNA sequence, whereas the invention here involves a combination of well known elements that create a generic biotechnological tool. Appellants further argue that the court erred by failing to conduct a factual inquiry as required by Capon v. Eshhar , 418 F.3d 1349, 1358 (Fed. Cir. 2005). Appellants contend that at the time of the invention, bot h DNA polymerase I and the polA gene were well known in the art. In addition, appell ants assert that the court improperly made factual determinations, improperly relied on the declaration of Roche’s expert while dismissing the declarations of its own ex perts, and failed to draw inferences in appellants’ favor. In response, Roche argues that the dist rict court correctly determined that the claims of the ’708 patent encompass more than the subject matter described in the specification and thus correctly found them invalid. Roche asserts that Eli Lilly applies to the present case as there was nothing in the Eli Lilly decision to suggest that that holding was limited to inventions involv ing novel DNA sequences. Roche further asserts that the court considered appellants’ evidence and correctly concluded that they failed to raise a genuine issue of material fact. We agree with Roche that t here is no genuine issue of material fact regarding whether the written descriptions of the ’708 and ’745 patents fail to adequately describe the claimed invention. We first consider the claims at issue. Claim 1 of the ’708 patent, a representative claim, recites:

2007-1266, -1267 121. A recombinant plasmid containing a cloned complete structural gene coding region isolated from a bacterial source for the expression of DNA polymerase I , under operable control of a conditionally controllable foreign promoter functionally linked to said structural gene coding region , said foreign promoter being functional to express said DNA polymerase I in a suitable bacterial or yeast host system. ’708 patent claim 1 (emphases added). Similarly, claims 1-3, and 23 of the ’745 patent, also representative claims, read as follows: 1. A recombinant plasmid contai ning a DNA coding sequence for the expression of DNA polymerase acti vity, wherein said DNA coding sequence is derived from a source that encodes a bacterial DNA Polymerase , said source not containing an amber mutation affecting expression of said DNA polymerase acti vity, such that when said plasmid is transformed into a bacterial hos t system the host system can grow and divide thereby replicating said plasmid. 2. The recombinant plasmid of clai m 1 wherein said DNA polymerase activity includes Nick-translation activity. 3. The plasmid of claim 2 wherein sa id Nick-translation activity is under operable control of a conditionally c ontrollable foreign promoter, said foreign promoter being functional to ex press said Nick-translation activity in said host system. 23. A method of producing an en zyme possessing DNA polymerase activity comprising the steps of: transforming a recombinant plasmid having a DNA coding sequence for the expression of DNA polymerase acti vity that is under operable control of a conditionally controllable forei gn promoter into a bacterial host system, said DNA polymerase coding sequence derived from a source that encodes a bacterial DNA polymerase , said source not containing an amber mutation affecting expression of said, DNA polymerase activity; and allowing the host system to grow and di vide for at least twenty generations thereby replicating said plasmid. ’745 claim 1-3, 23 (emphases added). The appealed claims of the ’ 708 patent are directed to re combinant plasmids that contain a DNA coding sequence that is br oadly defined, and only by its function, viz. , 2007-1266, -1267 13encoding DNA polymerase I. Mor eover, the generic claims are not limited to a single bacterial species, but broadly encompa ss coding sequences originating from any bacterial species. Similarly, the appealed cl aims of the ’745 patent are broadly directed to recombinant plasmids that contain a DNA coding sequence, again, only defined by function, viz. , encoding an enzyme with either DNA polymerase or nick-translation activity. Those claims are al so not limited to a single bacterial species, but cover all bacterial species. As a preliminary matter, we reject appe llants’ assertion that this case is distinguishable from Eli Lilly . Contrary to appellants’ assertion, nothing in Eli Lilly indicates that that holding was limited to inventions involving novel DNA sequences. Indeed, in University of Rochester , we rejected a similar argument. See Rochester , 358 F.3d at 925. In Eli Lilly , we held that “the claimed gener a of vertebrate and mammal cDNA [were] not described by t he general language of [a] patent ’s written description supported only by the specific nucleotide sequence of rat in sulin.” 119 F.3d at 1569. That holding was premised on the basic principle that a person of skill in the art must be able to “visualize or recognize the i dentity of the members of the genus.” Id. Thus, to satisfy the written description requirement for a claimed genus, a specification must describe the claimed invention in such a wa y that a person of skill in the art would understand that the genus that is being claimed has been invented, not just a species of the genus. The Guidelines for Examination of Pa tent Applications under the 35 U.S.C. § 112, ¶ 1, “Written Description” Require ment, 66 Fed. Reg. 10-99 (Jan. 5, 2001)

2007-1266, -1267 14(“Guidelines”), which we find to be an accu rate description of the law by the agency responsible for examining patent applications , and thus persuasive authority, provide further guidance for determining whether the wr itten description requirement is met for claims drawn to a genus. The Guidelines state: The written description requirement for a claimed genus may be satisfied through sufficient description of a repres entative number of species . . . by disclosure of relevant, identifying characteristics, i.e. , structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying c haracteristics, sufficient to show the applicant was in possession of the claimed genus. A “representative number of species” means that the species which are adequately described are represent ative of the entire genus . Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to refl ect the variation within the genus. * * * Satisfactory disclosure of a “repr esentative number” depends on whether one of skill in the art would recognize that the applicant was in possession of the necessary common attributes or features of the elements possessed by the members of the genus in view of the species disclosed. For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus

. Guidelines, 66 Fed. Reg. at 1106 (emphases added). Here, while the claims of the ’ 708 and ’745 patents encompass a genus of recombinant plasmids that contain c oding sequences for DNA polymerase or nicktranslation activity from any bacterial source, in contrast, the narrow specifications of the ’708 and ’745 patents only disclose the polA gene coding sequence from one bacterial
source, viz. , E. coli . Significantly, the specification fails to disclose or describe the polA gene coding sequence for any other bacterial species.

2007-1266, -1267 15The district court concluded that the disclosure of the E. coli polA gene was not representative of and failed to adequately suppor t the entire claimed genus. Based on the record evidence indicating a lack of a genuine issue of material fact on the issue, we agree. Notably, the record indicates that at the time of the invention, only three bacterial polA genes, viz. , E. coli , K. aerogenes , and K. pneumoniae , out of thousands of bacterial species had been cloned, and only E. coli was described in the patents. According to Roche’s expert, Dr. Bambara, bacteria constitute a large class of organisms that include thousands , and potentially millions, of unidentified species. In addition, at the time of the invention, persons of ordinary sk ill in the art knew that DNA polymerase I was not a single enzyme, but a family of enzymes enc oded by a family of genes that varied from one bacterial species to another. Dr. Bambar a stated that those enzymes were encoded by genes that were distinct from the E. coli polA gene. Significantly, the written descriptions of the ’708 and ’745 patents clearly indicate that the polA gene is critical to the claimed invent ion. Indeed, the pat ents disclose that a “significant discovery of the present in vention” involved t he need to severely damage the polA promoter sequence when constructing the recombinant plasmid in order to avoid the unregulated expression of DNA polym erase I, which otherwise would be lethal to the cell. ’708 patent col. 2 ll.40-46. The specifications disclose that “[t]he novel plasmid of the present invention contains t he entire and undamaged polA gene coding region enzymatically excis ed from a DNA molecule” and emphasize that “it is an important feature of this invention that the cloned polA gene fragment contains essentially none of or at the most only a portion of the acti vity of its natural promoter.” Id. col.2 ll.23-29.

2007-1266, -1267 16However, although the written descripti ons of the patents emphasize that the recombinant plasmids must be carefully constr ucted in order to ov ercome the lethality problem, particularly with r egard to the promoter, the patents fail to disclose the nucleotide sequence or other de scriptive features for a polA gene (including the promoter sequence) from any bacterial source other than E. coli . Indeed, in the Description of the Preferr ed Embodiments, the patents di sclose only one embodiment which uses the plasmid referred to as pMP5. The patents teach that pMP5 was constructed by taking the E. coli polA gene from phage NM825, cutting the polA gene specifically at the BglII restriction site, and splicing the polA gene into a plasmid pHUB2. 3 Id. col.5 ll.49-65, Fig. 1. The specification teaches that cutting the polA gene at the BglII restriction site was a significant discovery: We have discovered that the restri ction enzyme BglII will cut within the polA promoter sequence and severely dam age it. This is a significant discovery of the present invention, si nce it eliminates or greatly reduces the unregulated expression of Pol I, whic h would otherwise be lethal to the cell. Id. col.2 ll.40-46. As such, the patents t each that the specific gene sequence for the expression of DNA polymerase I or nick-transla tion activity is a critical aspect of the invention. We agree with the district court that the narrow disclosure of the E. coli polA gene is not representative of and fails to adequately support the entire claimed genus under Eli Lilly . To satisfy the written description r equirement in the ca se of a chemical or biotechnological genus, more than a statem ent of the genus is normally required.

3 The pMP5 plasmid was transformed into E. coli strain N4830, which resulted in strain ATL100. The written description of the patent discloses that ATL100 was deposited in the American Type Culture Collection Depository on June 29, 1984, under Accession number 39753. ’708 patent col.1 ll.36-41. 2007-1266, -1267 17One must show that one has possession, as described in the application, of sufficient species to show that he or she invented and disclosed the totality of the genus. In light of the specifications’ disclosure concerning the careful construction of the claimed recombinant plasmids, such that the natural promoter of the polA gene is severely damaged or eliminated, and given t he record evidence that the polA gene varied among the numerous bacterial species, as well as the absence of any polA gene sequence for any bacteria other than E. coli , we conclude that that requirement was not met here. We are unpersuaded by appellants’ assertion t hat a different result is warranted in light of our holding in Capon v. Eshhar , 418 F.3d 1349, 1358 (Fed. Cir. 2005). The inventions in Capon involved “chimeric DNA that encodes single-chain chimeric proteins for expression on the surface of cells of the immune system , plus expression vectors and cells transformed by the chimeric DNA.” Id. at 1352. We held that the Board of Patent Appeals and Interferences erred in holding that the written description requirement was not met because the disclosur es failed to “reiterat e the structure or formula or chemical name for the nucleotide sequences of t he claimed chimeric genes.” Id. at 1358. We explai ned that our holding in Eli Lilly did not impose “a per se rule requiring recitation in the specification of the nucleotide sequence of claimed DNA, when that sequence is already known in the field.” Id. at 1360-61. Moreover, we stated that “what is needed to support generic claims to biological subject matter depends on a variety of factors, such as the existing knowledge in the parti cular field, the extent and content of the prior art, the maturity of the science or technology, the predictability of the aspect at issue, and other considerations appropriate to the subject matter.” Id.

2007-1266, -1267 18Unlike the situation in Capon , however, where the prior art contained “extensive knowledge of the nucleotide stru cture of the various immune -related segments of DNA,” including “over 785 mouse antibody DNA li ght chains and 1,327 mouse antibody DNA heavy chains,” id. at 1355, the record here shows that only three bacterial polA genes out of thousands of genes had been cloned. As such, Capon does not aid appellants. Moreover, we disagree with appellants’ assert ion that the court failed to properly consider the Capon factors in its analysis. The cour t clearly considered the record evidence and properly determined the knowledge of one skilled in the field with respect to bacterial polA genes. We are further unpersuaded by appellants’ ar gument that the district court erred by failing to consider the declarations of t heir experts, which, according to appellants, create genuine issues of material fact. Appell ants primarily point to the declarations of Drs. Benkovic, Low, Hatfull, and Davis. Ha ving reviewed that evidence, we agree with the district court that they fail to create genuine issues of material fact. Appellants’ experts did not dispute the st atements made by Dr. Bambara that were material to the court’s invalidity holding under Eli Lilly . Indeed, it was undis puted that by 1984, only three bacterial polA genes had been cloned. Moreover, Dr. Davis agreed with Dr. Bambara’s statement that the polA gene “has different sequenc es for probably all the different bacterial species.” Carnegie Mellon Univ. v. Hoffmann-La Roche, Inc. , No. C 01-0415 SI, slip op. at 10 (N.D. Cal. Sept. 29, 2003). In addition, Dr. Benkovic agreed with Dr. Bambara’s assertion that the ’745 patent did not describe polA genes other than E. coli

. Id. at 11. The additional expert st atements relied upon by appellants, including statements concerning cloning techniques for purifying polA genes and

2007-1266, -1267 19experiments involving E. coli , were immaterial to the relevant inquiry and thus do not raise genuine issues of material fact. We have considered all of the remaini ng arguments appellants have raised in their briefs and found none that justify a reversal. Accordingly, because no genuine issues of material fact exist with regard to whether the written descriptions of the ’708 and ’745 patents adequately support the appealed claims, we affirm the district court’s grant of summary judgment of invalidity with respect to those claims.
2. The ’270 Patent Appellants argue that the district court e rred in concluding that the claims of the ’270 patent are invalid under our holding in Gentry Gallery . According to appellants, the court improperly invalidated the claims for lack of written description after concluding that they do not recite the problem the invention was intended to solve. Because lethality was the key problem solved by the claimed invent ion, appellants argue that it cannot be an “element” of the invention. In response, Roche argues that the court correctly concluded that the claims are invalid under Gentry Gallery because they were broadened during prosecution to encompass more than the subject matter described in the application. In the alter native, Roche asserts that even if the court erred in its analysis under Gentry Gallery , the claims are still invalid under Eli Lilly

. We agree with appellants that the district court erroneously found the claims invalid under Gentry Gallery . In reaching its decision, the court found clear and convincing evidence that “lethality was an ess ential feature of the invention claimed in the ’270 patent.” Carnegie Mellon , 1999 WL 3329545 at *7. T he court concluded that

2007-1266, -1267 20under Gentry Gallery , the claims were invalid bec ause the appealed claims did not contain that feature. In essence, the court applied an essential element test. As we said in Cooper Cameron Corp. v. Kvaerner Oilfield Products, Inc. , 291 F.3d 1317 (Fed. Cir. 2002), in Gentry Gallery “we did not announce a new ‘essential element’ test mandating an inquiry into what an inventor considers to be essential to his invention and requiring that the claims incorporate those elements.” Id. at 1323. Rather, “we applied and merely expounded upon the unremarkable pr oposition that a broad claim is invalid when the entirety of t he specification clearly indicates that the invention is of a much narrower scope.” Id. We thus agree wit h appellants that the district court erred by invali dating the claims of the ’270 patent by applying the essential element test. We further note that even if such a test ex isted, lethality was only a reason for the claimed invent ion, and not an element of it that needed to be defined in the claims. However, while the court erred in holding the claims of the ’270 patent invalid under Gentry Gallery , we agree with Roche t hat the claims are nonetheless invalid under Eli Lilly under the same rationale discussed above. The claims of the ’270 patent suffer the same defects as the appealed clai ms of the ’708 and ’745 patents. Indeed, the claims of the ’270 patent are also generic ally directed to plasmids encompassing the polA gene from any bacterial source. Thus , for the reasons set forth above, we conclude that there is no genuine issue of material fact as to whether the claims of the ’270 patent are invalid for lack of written description under Eli Lilly

. Accordingly, because the specifications of the ’708, ’745, and ’270 patents fail to provide adequate written description support for the appealed claims, all of which

2007-1266, -1267 21encompass a genus of recombinant plasmi ds containing gene coding sequences from any bacterial source, we affirm the distri ct court’s grant of summary judgment of invalidity. B. Noninfringement In view of our affirmance of the district court’s invalidity dec ision, the issue of infringement with respect to the asserted claims of the ’708 patent has become moot and will not be considered. We will, however, consider appellant’s argument with regard to the district court’s grant of summary j udgment of noninfringement of claims 4, 5, and 7 of the ’745 patent, as the validity of those claims has not been challenged and thus presumptively they remain valid. Claims 4, 5, and 7 of the ’745 patent are all dependent claims and they incorporate the claim limitati ons of claim 1. Those claims, however, are narrower in scope as they require E. coli as the bacterial source. Those claims read as follows: 1. A recombinant plasmid contai ning a DNA coding sequence for the expression of DNA polymerase acti vity, wherein said DNA coding sequence is derived from a source that encodes a bacterial DNA Polymerase , said source not containing an amber mutation affecting expression of said DNA polymerase acti vity, such that when said plasmid is transformed into a bacterial host system the host system can grow and divide thereby replicating said plasmid. 4. The recombinant plasmid of clai m 3 wherein the bacterial host system and the bacterial source are each E. coli ; and wherein the Nick-translation activity includes polymerase and 5'-3' exonuclease activities. 5. The recombinant plasmid of claim 4 wherein said foreign promoter is a negatively regulated promoter. 7. The recombinant plasmid of clai m 5 wherein said negatively regulated promoter is the leftward promoter of phage lambda. ’745 patent claims 1, 4, 5, & 7 (emphases added).

2007-1266, -1267 22On appeal, appellants argue that the district court err ed in concluding that the Roche’s pLSG5 product does not infringe the ’745 patent under the doctrine of equivalents. According to appe llants, the substitution of Taq for E. coli was an insubstantial and unimportant change that resulted in an infringing equivalent. Roche responds that the court correctly gr anted summary judgment of noninfringement because appellants’ infringement theory would vitiate the E. coli claim limitation of the appealed claims, which is impermissible under Warner-Jenkinson Co. v. Hilton Davis Chemical Co. , 520 U.S. 17 (1997). In addition, Ro che contends that, contrary to appellants’ assertion, the differences between Taq and E. coli are not insubstantial. We agree with Roche that the district court properly granted summary judgment of noninfringement under the doctrine of equivalent s. Under that doctr ine, “a product or process that does not litera lly infringe upon the express terms of a patent claim may nonetheless be found to infringe if there is ‘equivalence’ between the elements of the accused product or process and the claim ed elements of the pat ented invention.” Id. at 21 (citation omitted). Howeve r, the “all limitations rule ” restricts the doctrine of equivalents by preventing its application when doing so would vitiate a claim limitation. Id. at 29 (stating that the doc trine of equivalents cannot be applied broadly so as to “effectively eliminate that [claim] element in its entirety”). In determining whether a finding of infringement under the doctrine of equivalents would vitiate a claim limitation, we must consider “the totality of the circ umstances of each case and determine whether the alleged equivalent can be fa irly characterized as an insubstantial change from the claimed subject matter without rendering the pertinent limitat ion meaningless.” Freedman Seating Co. v. Am. Seating Co. , 420 F.3d 1350, 1359 (Fed. Cir. 2005).

2007-1266, -1267 232007-1266, -1267 24 We agree with Roche and the distri ct court that a finding that Taq is an equivalent of E. coli would essentially render t he “bacterial source [is] E. coli ” claim limitation meaningless, and would thus vitiate that limitation of the claims. Indeed, in drafting the claims, the patentees specifically chose to limit claim 4 to a recombinant plasmid where the bacterial source is E. coli . Appellants cannot now argue that any bacterial source, including Taq , would infringe that claim. Accordingly, summary judgment of noninfringem ent was appropriate. 4
CONCLUSION For the foregoing reasons, we affirm the district court’s grant of summary judgment of invalidity with r egard to claims 1-19, 22-40, and 43-45 of the ’708 patent, claims 1-2, 11-12, 14-15, 17-18, 20-21, 23-24, 26-27, 29-30, and 32-36 of the ’270 patent, and claims 3, 14, 23-28, and 30-32 of the ’745 patent. In addition, we affirm the court’s grant of summary judgment of noninfri ngement with respect to claims 4, 5, and 7 of the ’745 patent. AFFIRMED

4 We note, as Roche states in its briefs, that Taq DNA polymerase was and continues to be integral to the success of polymerase chain reaction (“PCR”), a widely used technique in molecular biology that was invented by Kary Mullis in 1983. Indeed, in 1993, Mullis won the Nobel Prize in Chemistry for his development of PCR and the journal Science named Taq DNA polymerase the “Molecule of the Year.” While we reach our decision irrespective of those fa cts, we readily can see why appellants have attempted to broaden the scope of their claims beyond the E. coli species disclosed.