Amgen Inc. v. F. Hoffmann-LaRoche LTD et al

Filing 821

MEMORANDUM in Support re #820 MOTION in Limine to Invoke Issue Preclusion as to Findings from Prior Litigation filed by F. Hoffmann-LaRoche LTD, Roche Diagnostics GmbH, Hoffmann LaRoche Inc.. (Attachments: #1 Exhibit A#2 Exhibit B#3 Exhibit C#4 Exhibit D#5 Exhibit E)(Brooks, Kregg)

Amgen Inc. v. F. Hoffmann-LaRoche LTD et al

Doc. 821 Att. 4

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Exhibit D
927 F. 2d 1200 927 F. 2d 1200, 59 USLW 2575, 18 U.S.P.Q.2d 1016 (Cite as: 927 F.2d 1200) Page 1

Amgen, Inc. v. Ch ugai Pharmaceutical Co., Ltd. C. A.Fed. (Mass. ),199 1. Un ited States Court of Appeals,Federal Circuit. AMGEN, INC., Plain tiff/Cross-Appellan t, v. CHUGAI PHARMACEUTICAL CO., LT D., an d Gen etics Institute, In c., Defen dants-Appellan ts. Nos. 90-1273, 90-1275. March 5, 1991. Suggestion for Rehearing In Ban c Declined May 20, 1991. Owner of paten t for DNA sequen ces encodin g Erythropoietin (EPO) brough t suit against owner of paten t for method for purification of E PO and E PO composition s, claimin g patent infrin gement, an d seekin g declaration that defen dant's paten t was in valid or, in th e altern ative, that plaintiff did not in fringe claims of th e paten t, and declaration that defen dants' future activities in the production and sale of E PO would infringe plain tiff's paten t. Defen dan ts counter claimed, allegin g paten t in frin gement an d un fair composition, an d seekin g declar atory judg ment that plain tiff's paten t was invalid an d not in fringed. The United States District Court for th e District of Massach usetts, William G. Youn g, J., ruled that some claims of plain tiff's patent were valid an d in fringed, th at oth er claims were in valid, but if valid, were infr inged, and that some claims of defen dant's patent were valid and infrin ged, that some claim s were n ot infrin ged an d that oth er claims were in valid for in definiten ess. Both parties appealed. The Court of Appeals, Lourie, Circuit Judge, h eld th at: (1) plaintiff's in vention had priority; (2) claim s for plaintiff's paten t wer e not obvious; (3) plain tiff's paten t satisfied best mod e requirement; (4) generic DNA sequen ce claim s of plaintiff's patent did n ot satisfy enablement requirement; (5) there was n o in equitable con duct in prosecution of plain tiff's paten t; (6) claims for defen dan t's paten t were not adequately en abled; and (7) oth er claim s for defen dant's patent wer e indefin ite. Affirmed in part, reversed in part and vacated in part. West Headn otes [1] Patents 291 90(1)

291 Paten ts 291III Person s Entitled to Paten ts 291k90 Original In ventors and Priority Between In ventors 291k90(1) k. In Gen eral. Most Cited Cases " Conception ," in determining priority of in vention , is th e formation in th e min d of th e in ventor of a definite an d perman ent idea of the complete an d operative in ven tion , as it is h ereafter to be applied in practice; con ception requires both th e idea of th e in ven tion 's structure and possession of an operative m eth od of making it. 35 U.S.C.A. § 102(g). [2] Patents 291 90(1)

291 Paten ts 291III Person s Entitled to Paten ts 291k90 Original In ventors and Priority Between In ventors 291k90(1) k. In Gen eral. Most Cited Cases Th e con ception for purified an d isolated DNA sequen ces encodin g human erythropoietin (E PO) did n ot occur, for purposes of determinin g pr iority of in ven tion , until gen e had been isolated; before th e gen e was clon ed, th e amin o acid sequen ce for EPO was un certain, an d in some positions th e sequen ce en vision ed was in corr ect. 35 U.S.C. A. § 102(g). [3] Patents 291 90(1)

291 Paten ts 291III Person s Entitled to Paten ts 291k90 Original In ventors and Priority Between In ventors 291k90(1) k. In Gen eral. Most Cited Cases Conception of chemical compoun d, for purposes of prior ity of in ven tion, requires that in ventor be able to define it so as to distin guish from oth er materials, and to describe how to obta in it; conception does n ot occur un less on e has a mental picture of th e structure of th e chemical, or is able to defin e it by its meth od of pr eparation, its physical or ch emical properties, or whatever characteristics sufficiently distinguish it. [4] Patents 291 90(5)

291 Paten ts 291III Person s Entitled to Paten ts 291k90 Original In ventors

and

Priority

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927 F. 2d 1200 927 F. 2d 1200, 59 USLW 2575, 18 U.S.P.Q.2d 1016 (Cite as: 927 F.2d 1200) Bet ween In ven tors 291k90(5) k. Reduction of Inven tion to Practice in Gen eral. Most Cited Cases When in ventor is unable to en vision detailed con stitution of gene so as to distinguish it from other materials, as well as meth od for obtain ing it, con ception, for purposes of priority of in ven tion, h as n ot been ach ieved until reduction to practice has occurred, i.e., until after gene h as been isolated. 35 U. S. C.A. § 102(g). [5] Patents 291 17(3)

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291 Paten ts 291IV Application s and Proceedin gs Ther eon 291k99 k. Description of In ven tion Specification. Most Cited Cases Patents 291 167(1)

in

291 Patents 291II Patentability 291II(A) Inven tion ; Obviousn ess 291k17 Nature an d Degree of Skill In volved 291k17(3) k. Particular Devices or Processes. Most Cited Cases Un ique probing an d screening meth od employed b y in ven tor in isolating human erythropoietin (EPO) gene was n ot obvious. 35 U. S. C. A. § 103. [6] Patents 291 99

291 Paten ts 291IX Con struction and Operation of Letters Patent 291IX(B) Lim itation of Claims 291k167 Specification s, Drawings, an d Models 291k167(1) k. In General. Most Cited Cases Applicant for paten t for DNA sequence en codin g er ythr opoietin (E PO), an organism created by in ser tion of genetic material into cell obtain ed from gen erally availa ble sources, was not requir ed to place cell samples in public depository, where best mode of preparin g cells had been disclosed, and cells could be prepared by on e skilled in th e art from kn own m aterials usin g description in th e specification . 35 U.S.C. A. § 112. [9] Patents 291 99

291 Patents 291IV Applications and Proceedin gs Th ereon 291k99 k. Description of Inven tion in Specification . Most Cited Cases Absen t in equitable con duct, best mode defen se only affects th ose claims coverin g subject matter the practice of wh ich has n ot been disclosed in complian ce with best mode requirement. 35 U.S.C. A. § 112. [7] Patents 291 99

291 Patents 291IV Applications and Proceedin gs Th ereon 291k99 k. Description of Inven tion in Specification . Most Cited Cases In determin in g wh eth er paten t application sets forth best mode con templated by in ventor of carryin g out his in ven tion, court inquires wh eth er, at time in ventor filed his patent application, he con templated a best mode of practicin g h is in vention, an d if h e did, wh eth er his disclosure is adequate to en able on e skilled in th e art to practice th e best mode, or, in oth er words, whether best mode had been con cealed from the public. 35 U.S.C. A. § 112. [8] Patents 291 99

291 Paten ts 291IV Application s and Proceedin gs Ther eon 291k99 k. Description of In ven tion in Specification. Most Cited Cases Wh en organism is created by insertion of genetic m aterial into cell obtained from generally availa ble sources, best mode requiremen t is satisfied by description of the best mode and adequate description of means of carrying out the in ven tion, n ot a deposit of th e cells; if the cells can be prepared with out undue experimentation from known materials, based on the description in the patent specification, a deposit is n ot required. 35 U. S. C.A. § 112. [10] Patents 291 113(6)

291 Paten ts 291IV Application s and Proceedin gs Ther eon 291k113 Appeals from Decisions of Commission er of Paten ts 291k113(6) k. Review on Appeal in General. Most Cited Cases Wh eth er wr itten description of in vention is sufficient to en able per son skilled in th e art to make and use th e

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927 F. 2d 1200 927 F. 2d 1200, 59 USLW 2575, 18 U.S.P.Q.2d 1016 (Cite as: 927 F.2d 1200) same is a question of law, which Court of Appeals reviews de novo. 35 U.S.C. A. § 112. [11] Patents 291 99

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best mode and enablemen t requiremen ts. 35 U.S.C.A. § 112. [15] Patents 291 97

291 Patents 291IV Applications and Proceedin gs Th ereon 291k99 k. Description of Inven tion in Specification . Most Cited Cases That some experimentation is n ecessary to make or use claim ed in ven tion does not constitute lack of en ablement; amoun t of experim entation , however, must not be un duly excessive. 35 U.S.C. A. § 112. [12] Patents 291 99

291 Paten ts 291IV Application s and Proceedin gs Ther eon 291k97 k. Patent Office an d Proceedin gs Th erein in General. Most Cited Cases Central elements of proof of in equitable conduct by paten t applicant include inten t to deceive an d m ateriality; after finding thresh old levels of m ateriality an d intent, trial court must balan ce th e two and determin e, in its discretion, wh eth er in equitable conduct has occurred. [16] Patents 291 324.5

291 Patents 291IV Applications and Proceedin gs Th ereon 291k99 k. Description of Inven tion in Specification . Most Cited Cases Gen eric claim, coverin g all possible DNA sequen ces th at would en code an y polypeptide h aving amin o acid sequen ce " sufficien tly dup licative" of erythropoietin (E PO) to possess the property of in creasing production of red blood cells failed to disclose h ow to make an d use enough sequences to justify gr an t of claim sough t; paten t claimed ever y possible analog of a gen e con taining about 4,000 n ucleotides, with disclosure of h ow to make EPO and a very few analogs. 35 U. S. C.A. § 112. [13] Patents 291 99

291 Paten ts 291 XII Infringement 291XII(C) Suits in Equity 291k324 Appeal 291k324.5 k. Scope an d E xten t of Review in Gen eral. Most Cited Cases Court of Appeals reviews ultimate con clusion of in equitable con duct by paten t applican t under abuse of discretion stan dar d, but underlyin g factual threshold findin gs are reviewed un der clearly erron eous stan dard. [17] Patents 291 97

291 Patents 291IV Applications and Proceedin gs Th ereon 291k99 k. Description of Inven tion in Specification . Most Cited Cases It is not n ecessary th at paten t applicant test all embodim ents of his in vention; what is n ecessary is th at h e provide disclosure sufficien t to enable one skilled in the art to carry out th e in vention commen surate with th e scope of h is claims. 35 U. S. C.A. § 112. [14] Patents 291 101(1)

291 Patents 291IV Applications and Proceedin gs Th ereon 291k101 Claims 291k101(1) k. In General. Most Cited Cases Patent applican t is en titled to claim h is in vention generically, wh en h e describes it sufficiently to meet

291 Paten ts 291IV Application s and Proceedin gs Ther eon 291k97 k. Patent Office an d Proceedin gs Th erein in General. Most Cited Cases Th ere was n o in equitable con duct in prosecutin g paten t for DNA sequen ces en coding erythropoietin (EPO); that in ven tor did n ot recall wh eth er h e first used screen ed mon key cDNA library with full set of probes or subset of pr obes, an d his an swer that " it looks like" he used th e subset, were n ot clear admissions that he used on ly a su bset, and even if th er e h ad been an erron eous statement, it was n ot m aterial, as in ventor succeed ed en codin g th e E PO gen e first with his use of full y-degen erate probes. [18] Patents 291 101(5)

291 Paten ts 291IV Application s and Proceedin gs Ther eon

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927 F. 2d 1200 927 F. 2d 1200, 59 USLW 2575, 18 U.S.P.Q.2d 1016 (Cite as: 927 F.2d 1200) 291k101 Claims 291k101(5) k. Requisites an d Sufficiency. Most Cited Cases Claims for paten t for method for purification of th e erythropoietin (E PO) an d EPO composition s, requirin g 160,000 IU/AU by in vivo measurement, were n ot adequately enabled; in vivo data did not support claims contain ing an in vivo limitation . 35 U. S. C.A. § 112. [19] Patents 291 101(5)

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291IV Application s and Proceedin gs Ther eon 291k97 k. Patent Office an d Proceedin gs Th erein in General. Most Cited Cases T o establish in equita ble conduct with respect to paten t, intent to deceive is r equired. [23] Patents 291 97

291 Patents 291IV Applications and Proceedin gs Th ereon 291k101 Claims 291k101(5) k. Requisites an d Sufficiency. Most Cited Cases Whether patent claim satisfies requirement th at " [t]he specification shall conclude with on e or mor e claims particularly poin ting out and distin ctly claimin g th e subject matter which the applican t regards as his invention" requires determination wh eth er th ose skilled in th e art would un derstan d wh at is claimed. 35 U. S. C.A. § 112. [20] Patents 291 101(6)

291 Paten ts 291IV Application s and Proceedin gs Ther eon 291k97 k. Patent Office an d Proceedin gs Th erein in General. Most Cited Cases Findin g of intent to deceive, required to esta blish in equitable con duct with respect to paten t, may follow from assessment of materiality, kn owledge, an d surroun din g circumstances, including eviden ce of good faith . [24] Patents 291 97

291 Patents 291IV Applications and Proceedin gs Th ereon 291k101 Claims 291k101(6) k. Ambiguity, Un cer tainty or In defin iten ess. Most Cited Cases Claims of paten t for meth od of pur ification of erythropoietin (EPO) and EPO composition s were in valid because th eir specific activity limitation of " at least about 160, 000" was indefin ite. 35 U.S.C. A. § 112. [21] Patents 291 101(6)

291 Paten ts 291IV Application s and Proceedin gs Ther eon 291k97 k. Patent Office an d Proceedin gs Th erein in General. Most Cited Cases Th ere was n o inequitable conduct with respect to paten t for method for purification of er ythropoietin (EPO) an d EPO composition s, despite con tention that paten t own er displayed in tent to mislead by withh olding data showing in vivo specific activity of h omogen eous EPO and withholding in formation on range of error in EPO bioassa ys. Patents 291 328(2)

291 Patents 291IV Applications and Proceedin gs Th ereon 291k101 Claims 291k101(6) k. Ambiguity, Un cer tainty or In defin iten ess. Most Cited Cases When meanin g of paten t claim s is in doubt, especially wh en th ere is close prior art, th ey are properly declared in valid. 35 U.S.C.A. § 112. [22] Patents 291 291 Patents 97

291 Paten ts 291 XIII Decision s on th e Validity, Con struction, and Infringemen t of Particular Patents 291k328 Patents Enumerated 291k328(2) k. Origin al Utility. Most Cited Cases 4, 677,195. Claims 1, 3, 4, 6 invalid. Patents 291 328(2)

291 Paten ts 291 XIII Decision s on th e Validity, Con struction, and Infringemen t of Particular Patents 291k328 Patents Enumerated 291k328(2) k. Origin al Utility. Most Cited Cases 4, 703,008. Claims 2, 4, 6, valid and infrin ged claim s 7, 8, 23-27, 29 invalid.

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927 F. 2d 1200 927 F. 2d 1200, 59 USLW 2575, 18 U.S.P.Q.2d 1016 (Cite as: 927 F.2d 1200)

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*1202 E dward M. O'Toole,Marsh all, O'Toole, Gerstein , Murray & Bicknall, Chicago, Ill., argued, for plaintiff/cross-appellant. With him on the brief were Mich ael F. Borun, Rich ard A. Schnurr an d Christin e A. Dudzik. Also on the brief were Steven M. Odre an d Robert D. Weist, Amgen, In c. , Thousan d Oaks, Cal. , of counsel. Kurt E. Richter, Morgan & Finnegan , New York City, and William F. Lee, Hale & Dorr, Bost on , Mass., argued for defendan ts-appellants. Of coun sel were Eugene Moroz, Michael P. Dougher ty an d William S. Feiler, Morgan & Finn egan, New York City. Before MARKE Y, LOURIE an d CLEVE NGER, Circuit Judges. LOURIE , Cir cuit Judge. This appeal an d cross appeal are from th e Mar ch 4, 1990, judgmen t of th e United States District Court for th e District of Massach usetts, A mgen, Inc. v. Chugai Pharmaceutical Co ., 13 USPQ2d 1737, 1989 WL 169006 (1990), and involve issues of paten t validity, in fringemen t, an d in equitable con duct with respect to two patents: U. S. Patent 4, 703,008 ('008), own ed by Kirin-Amgen In c. (Amgen ), and U.S. Patent 4,677,195 ('195), own ed by Gen etics In stitute, In c. (GI). *1203 Chugai Pharmaceutical Co., Ltd. (Ch ugai) an d Gen etics In stitute, Inc. (collectively defendan ts) assert on appeal that the district court erred in h oldin g th at: 1) Amgen's '008 paten t is n ot invalid under 35 U. S. C. §§ 102(g) an d 103; 2) th e '008 patent is en forceable; 3) th e failure of Amgen to deposit th e best mode host cells was n ot a violation of the best mode requiremen t under 35 U.S.C. § 112; and 4) claims 4 an d 6 of GI's '195 paten t are invalid for in defin iteness un der 35 U.S. C. § 112. On cross appeal, Amgen ch allenges th e district court's h oldin gs that: 1) claims 1 an d 3 of th e '195 paten t are enabled; 2) th e '195 patent is enforceable; 3) this is n ot an exceptional case warranting an award of attorney fees to Amgen ; an d 4) claims 7, 8, 23-27 an d 29 of th e '008 patent are not en abled by th e specification. We affirm th e district court's h oldin gs in all respects, except th at we reverse th e court's rulin g that claims 1 an d 3 of th e '195 paten t are en abled. We also vacate th at part of the district court's judgmen t relating to in fringement of th ose claims.

BACKGROUND FN1 FN1. Th e district court, in a detailed opin ion , fully sets out th e scien tific an d historical backgroun d relating to th e patents at issue. See Amgen, 13 USPQ2d at 1741-58. Familiarity with that opin ion is presumed. Erythropoietin (E PO) is a protein con sisting of 165 amino acids wh ich stim ulates th e production of red blood cells. It is th erefore a useful th erapeutic agent in th e treatment of an emias or blood disorders ch aracterized by l ow or defective bone m arrow production of r ed blood cells. Th e preparation of EPO products gen erally has been accomplish ed through th e concen tration an d purification of urine from both h ealthy in dividuals an d th ose exhibitin g high EPO levels. A n ew techn ique for producin g E PO is recombinant DNA techn olog y in which EPO is produced from cell cultures into wh ich genetically-en gin eered vectors con tainin g th e E PO gen e have been introduced. Th e production of EPO by recombin ant technolog y in volves expressin g an EPO gen e through th e same processes that occur in a natur al cell. THE PATE NT S On June 30, 1987, the Un ited States Paten t an d Trademark Offic e (PT O) issued to Dr. Rodn ey Hewick U. S. Patent 4,677,195, entitled " Meth od for th e Purification of E r yth ropoietin and Erythropoietin Composition s" (th e '195 patent). The paten t claim s both homogeneous EPO an d composition s th ereof an d a method for purifyin g h uman EPO using r everse phase high perfor mance liquid chromatograph y. Th e m eth od claims are n ot before us. Th e relevan t claim s of th e '195 paten t ar e: 1. Homog eneous er ythropoietin ch aracterized by a m olecular weight of about 34,000 dalton s on SDS PAGE, m ovemen t as a single peak on reverse phase high performan ce liquid chr omatograph y an d a specific activity of at least 160,000 IU per absorbance unit at 280 nanometer s. ****** 3. A pharmaceutical composition for th e treatm ent of an emia comprisin g a th erapeutically effective amount of the h omogen eous er ythropoietin of claim 1 in a pharmaceutically acceptable veh icle.

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927 F. 2d 1200 927 F. 2d 1200, 59 USLW 2575, 18 U.S.P.Q.2d 1016 (Cite as: 927 F.2d 1200) 4. Homogen eous er ythropoietin characterized by a molecular weigh t of about 34,000 dalton s on SDS PAGE, movement as a sin gle peak on reverse phase high perfor mance liquid chromatograph y an d a specific activity of at least about 160, 000 IU per absorban ce un it at 280 n anometers. ****** 6. A phar maceutical composition for the treatmen t of an emia comprising a th erapeutically effective amount of th e h omogen eous er ythropoietin of claim 4 in a pharmaceutically acceptable veh icle. Dr. Hewick assigned the paten t to GI. The oth er paten t in this litigation is U.S. Paten t 4,703,008, entitled " DNA Sequen ces En codin g Erythropoietin" (th e '008 paten t), issued on October 27, 1987, to Dr. Fu-Kuen Lin, an employee of Amgen. The claims of *1204 the '008 paten t cover purified an d isolated DNA sequen ces en codin g erythropoietin an d h ost cells transformed or tr an sfected with a DNA sequen ce. Th e r elevan t claims are as follows: 2. A purified and isolated DNA sequen ce con sistin g essen tially of a DNA sequen ce en codin g h uman erythropoietin. ****** 4. A procaryotic or eucaryotic h ost cell transformed or tran sfected with a DNA sequen ce accordin g to claim 1, 2 or 3 in a mann er allowin g th e host cell to express erythropoietin . ****** 6. A procaryotic or eucaryotic host cell sta bl y tr an sformed or transfected with a DNA vector accordin g to claim 5. 7. A purified and isolated DNA sequen ce con sistin g essen tially of a DNA sequen ce en coding a polypeptide havin g an amino acid sequen ce sufficiently duplicative of th at of er ythropoietin to allow possession of the biological property of causin g bone marrow cells to in crease production of reticulocytes an d red blood cells, and to in crease h emoglobin syn th esis or iron uptake. 8. A cDNA sequen ce according to claim 7. ****** 23. A pr ocaryotic or eucaryotic host cell transformed or tran sfected with a DNA sequen ce accordin g to claim 7, 8, or 11 in a mann er allowing th e h ost cell to express said polypeptide. PROCE DURA L HIST ORY

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24. A tran sformed or tran sfected h ost cell accordin g to claim 23 which h ost cell is capable of glycosylating said polyp eptide. 25. A tran sformed or transfected mammalian h ost cell according to claim 24. 26. A tran sformed or transfected COS cell accordin g to claim 25. 27. A tr an sformed or tran sfected CHO cell accordin g to claim 25. ****** 29. A procaryotic h ost cell stably transform ed or tran sfected with a DNA vector according to claim 28.

On October 27, 1987, th e same day that the '008 paten t was issued, Amgen filed suit again st Ch ugai an d GI. It alleged th at GI infrin ged th e '008 paten t by th e production of r ecombin an t EPO (rE PO) and by use of transfor med mammalian host cells con tainin g vectors with DNA codin g for th e production of h uman E PO, an d that Chugai, as a result of a collaborative relation ship with GI, had induced an d/or contributed to th e direct in fringemen t of th e '008 paten t by GI. Amgen furth er sought a declaration that GI's '195 patent is in valid under 35 U.S.C. §§ 102, 103, an d 112, or, in th e alternative, th at Amgen does n ot in fringe the claims of th e '195 paten t, an d a declaration th at GI and Chugai's future activities in th e production and sale of rEPO will in fringe th e '008 paten t. FN2 FN2. Amgen subsequently filed a complaint with th e Un ited States Internation al Trade Commission alleging that Chugai's importation of r EPO, manufactured in Japan using genetically en gin eer ed h ost cells, violated Section 337 of th e Tariff Act of 1930 (19 U.S.C. § 1337, 1337a). Th e Commission en ter ed an order terminatin g th e investigation for lack of su bject matter jurisdiction. Th is court vacated an d remanded, h oldin g th at the Commission should have treated the complain t on th e merits and n ot on jurisdictional groun ds, and th at th e claims of Amgen 's patent did n ot cover a process for producing r EPO. A mgen, Inc. v. United States Int'l Trade Comm'n, 902 F. 2d 1532, 14 USPQ2d 1734 (Fed.Cir. 1990).

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927 F. 2d 1200 927 F. 2d 1200, 59 USLW 2575, 18 U.S.P.Q.2d 1016 (Cite as: 927 F.2d 1200) GI an d Chugai an swered an d counterclaimed, asserting several affirmative defen ses, in cludin g in validity under 35 U.S.C. §§ 101, 102, 103, and 112; n on-in frin gement; failure to make deposits at a public depositor y of biological materials allegedly n ecessar y for enablin g the best mode of practicin g the in ven tion ; and unen forceability of th e paten t because of Amgen's alleged inequitable con duct before the PTO. GI also coun terclaimed, allegin g th at Amgen in fringed th e '195 patent, assertin g un fair competition, and seekin g a declaratory judgment that th e '008 paten t was invalid and not in fringed. GI and Chugai then filed a join t motion for a partial summary judgment that Amgen *1205 in frin ged the claims of th e '195 patent. Chugai also filed its own motion for summary judgment. On February 24, 1988, th e district court granted GI's and Ch ugai's motion for partial summary judgmen t an d, on Januar y 31, 1989, th e court gran ted Ch ugai's motion for partial summary judgment on ly to th e exten t of ruling that th e '008 paten t does n ot contain a process claim, an issue that is n ot n ow before us. In respon se to Am gen's motion for a preliminary in jun ction, the district court, on February 7, 1989, issued an order finding that " Amgen had sh own a reasonable likelihood of success on the merits of the validity of its patent; th at it would suffer irreparable in jury due to th e n eeds of an in cipient market and the attendan t burden s on a n ew compan y; .. ." an d that, as to th e public interest, " recombinan t E PO is an extraordin arily valuable medicin e that promises marked relief from renal failure." Because of th is public interest finding, the court determin ed that it would n ot en ter an order to delay or preven t production or sh ipping of EPO, but would require th e defen dant GI to place with th e court all profits fr om th e sale of EPO. In order to expedite trial, th e parties con sen ted to trial before a magistrate. The judge enter ed judgmen t upon fin dings of fact and con clusions of law set forth by the magistrate. With respect to Amgen's '008 paten t, th e cour t h eld that claims 2, 4, and 6 ar e valid, en forceable an d h ave been in frin ged by GI; that in fringement was n ot willful; that claims 7, 8, 23-27, an d 29 are in valid for lack of en ablement under 35 U. S. C. § 112 but, if valid, were infringed by GI; that th e '008 paten t does n ot con tain a process claim; an d th at Ch ugai h as n ot infrin ged, contributorily in fringed, or in duced in fringemen t of any claim of th e '008 patent. Th e court also dismissed Amgen 's complain t again st Chugai.

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With respect to GI's '195 paten t, th e court concluded th at claims 1 and 3 are valid, en forceable, an d have been in fringed by Amgen ; that Amgen has n ot in fringed claim s 2 an d 5; that Amgen's in frin gement was not willful; an d th at claims 4 an d 6 are in valid for indefin iten ess under 35 U. S.C. § 112, but, if valid, were in frin ged by Amgen. Th e court also concluded th at Amgen did n ot misuse the '008 paten t an d that th is was n ot an " exception al" case un der 35 U.S.C. § 285. DISCUSSION I. AMGE N's '008 PATENT (Lin ) A. A lleged prior invention under 35 U. S.C. § 102(g) Th e fir st issue we review is wh eth er the district court erred in fin din g that the claims directed to a purified an d isolated DNA sequence encodin g h uman E PO were n ot in validated by th e work of GI's Dr. Fritsch. Section 102(g) provides in r elevan t par t that: A person is entitled to a paten t un less(g) before the applicant's in vention th ereof th e in ven tion was made . .. by an other wh o had n ot abandon ed, suppr essed, or con cealed it. In determin ing pr iority of in ven tion there shall be con sidered n ot on ly th e respective dates of con ception and reduction to practice of th e in vention, but also the reason able diligen ce of on e wh o was first to conceive and last to reduce to practice, from a time prior to con ception by the other. Defendants assert error in th e district court's legal con clusion that in th is case Lin 's conception occurred simultan eously with reduction to practice. See e.g., Hybritech Inc. v. Monoclonal A ntibodies, Inc., 802 F.2d 1367, 137 6, 231 USPQ 81, 87 (Fed.Cir.1986), cert. denied, 480 U. S. 947, 107 S.Ct. 1606, 94 L.E d.2d 792 (1987) . Th ey claim that Fritsch was first to con ceive a probin g strategy of usin g two sets of fully-degen erate cDNA probes of two different r egion s of the E PO gen e to screen a gDNA libr ar y, which was th e strateg y wh ich th e district court foun d even tually resulted in th e successful iden tification an d isolation of th e E PO gen e. Defen dants fur th er claim th at Fritsch con ceived this strategy in 1981, was diligen t until h e reduced th e in vention to practice in May of 1984, an d th us should be held to be a § 102(g) prior *1206 in ventor over Lin, wh o reduced

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Case 1:05-cv-12237-WGY

Document 821-5

Filed 08/16/2007

Page 8 of 19

927 F. 2d 1200 927 F. 2d 1200, 59 USLW 2575, 18 U.S.P.Q.2d 1016 (Cite as: 927 F.2d 1200) th e invention to practice in September of 1983. [1] Conception is th e " formation in the mind of the in ven tor, of a defin ite and perman ent idea of the complete an d operative in vention, as it is h ereafter to be applied in practice." Hybritech, 802 F. 2d at 1376, 231 USPQ at 87 (citin g 1 R obinson on Patents 532 (1890)); Coleman v. Dines, 754 F.2d 353, 359, 224 USP Q 857, 862 (Fed. Cir.1985) (citing Gunter v. Stream, 573 F.2d 77, 80, 197 USPQ 482, 484 (CCPA 1978)). Con ception r equir es both th e idea of th e in ven tion 's structure and possession of an operative meth od of makin g it. Oka v. Youssefyeh, 849 F.2d 581, 583, 7 USPQ2d 1169, 1171 (Fed. Cir.1988). [2] In some in stan ces, an in ventor is un able to establish a conception un til h e has reduced the in ven tion to pr actice through a successful exper iment. This situation results in a simultan eous con ception an d reduction to practice. See 3 D. Chisum, Patents § 10. 04[5] (1990). We agree with th e district court th at th at is what occurr ed in th is case. The inven tion recited in claim 2 is a " purified an d isolated DNA sequence" encoding h uman E PO. The structure of this DNA sequence was un known until 1983, wh en th e gen e was cloned by Lin; Fritsch was unaware of it un til 1984. As Dr. Sadler, an expert for GI, testified in his deposition : " You h ave to clon e it first to get th e sequen ce." In order to design a set of degen erate pr obes, one of wh ich will hybridize with a particular gene, th e amin o acid sequen ce, or a portion th ereof, of th e protein of in terest must be known . Prior to 1983, th e amino acid sequence for EPO was un certain, an d in some position s th e sequen ce en vision ed was incorrect. Thus, until Fritsch h ad a complete mental conception of a purified and isolated DNA sequen ce encodin g EPO and a meth od for its preparation, in wh ich the precise iden tity of the sequence is en vision ed, or in terms of other ch aracteristics sufficien t to distin guish it from other genes, all h e h ad was an objective to make an in ven tion wh ich he could not th en adequately describe or define. [3][4] A gen e is a ch emical compound , albeit a complex one, an d it is well establish ed in our law that con ception of a chemical compoun d requires th at the in ven tor be able to defin e it so as to distinguish it from other materials, and to describe h ow to obtain it. See Oka, 849 F. 2d at 583, 7 USPQ2d at 1171. Con ception does n ot occur unless on e has a men tal

Page 8

picture of th e structure of the chemical, or is able to define it by its meth od of preparation, its physical or ch emical properties, or whatever characteristics sufficien tly distin guish it. It is not sufficien t to defin e it solely by its prin cipal biological property, e.g., en codin g h uman erythropoietin, because an alleged con ception havin g n o more specificity th an that is simply a wish to know the iden tity of an y material with that biological property. We hold that when an in ven tor is unable to en vision the detailed con stitution of a gene so as to distin guish it from other materials, as well as a meth od for obtain ing it, con ception has n ot been ach ieved until reduction to practice h as occurr ed, i.e., un til after th e gene h as been isolated. Fritsch had a goal of obtaining th e isolated E PO gen e, whatever its identity, and even had an idea of a possible meth od of obtain in g it, but he did n ot con ceive a purified and isolated DNA sequen ce en codin g E PO and a viable meth od for obtaining it until after Lin . It is important to recogn ize that n eith er Fritsch n or Lin in vented E PO or th e E PO gen e. The subject matter of claim 2 was the n ovel purified and isolated sequen ce wh ich codes for E PO, an d neith er Fritsch n or Lin knew the structure or ph ysical ch aracteristics of it an d h ad a viable method of obtaining that subject matter until it was actually obtained and characterized. Defendants further ar gue that because th e trial cour t foun d that th e probin g and screenin g method employed by Lin is what distinguish ed th e inven tion of th e '008 patent over th e prior art, Fritsch's strategy in 1981 had priority over Lin 's use of th at strategy. We disagree. The trial court foun d that Fritsch 's alleged con ception in 1981 of an approach that might r esult in clonin g the gen e was mere speculation. *1207 Con ception of a gen eralized approach for scr een in g a DNA library th at might be used to identify and clon e the E PO gen e of then unkn own con stitution is not conception of a " purified an d isolated DNA sequen ce" en coding h uman EPO. It is n ot " a defin ite and perman ent idea of th e complete an d operative in vention." Fritsch's conception of a process h ad to be sufficien tly specific that on e skilled in th e relevant art would succeed in cloning the E PO gen e. See Coleman, 754 F.2d at 359, 224 USPQ at 862 . Clearly, h e did n ot h ave th at con ception because h e did not kn ow th e structure of EPO or th e E PO gen e.

© 2007 Thomson/West. No Claim to Orig. U.S. Govt. Works.

Case 1:05-cv-12237-WGY

Document 821-5

Filed 08/16/2007

Page 9 of 19

927 F. 2d 1200 927 F. 2d 1200, 59 USLW 2575, 18 U.S.P.Q.2d 1016 (Cite as: 927 F.2d 1200) The record indicates that sever al companies, as well as Amgen and GI, wer e un successful using Fritsch 's approach. As the trial cour t correctly summarized: Given th e utter lack of experien ce in probin g genomic libraries with fully degen erate probes an d th e crudeness of th e techniques available in 1981, it would h ave been mere speculation or at most a probable deduction from facts th en kn own by Dr. Fritsch that his generalized approach would result in clon in g th e E PO gene. 13 USPQ2d at 176 0. As expert testimon y from both sides indicated, success in clon in g th e E PO gen e was n ot assured until th e gene was in fact isolated an d its sequence known . Based on th e un certain ties of th e meth od an d lack of information con cerning the amin o acid sequence of the EPO protein , th e trial court was correct in con cluding that neith er party h ad an adequate con ception of the DNA sequen ce un til reduction to practice h ad been achieved; Lin was first to accomplish that goal. Defen dants also argue that th e cour t failed to con sider that 1983, just prior to Lin's con ception, was th e r elevan t time for determin ing the completen ess of Fritsch's con ception, n ot 1981. However, th e record sh ows th at th e court did con sider what occurred in 1983. Moreover, Fritsch had n o mor e of a con ception in 1983 than he did in 1981, because h e did not th en kn ow th e sequence of the gen e en codin g E PO. B. Alle ged obviousness of the inventions of claims 2, 4, and 6 Claim 2, as n oted above, recites a purified an d isolated DNA sequ en ce, and claims 4 an d 6 are directed to h ost cells tran sformed with such a DNA sequence. Th e district court determin ed that claims 2, 4, an d 6 are n ot invalid un der 35 U.S.C. § 103, con cluding that th e un ique probin g an d screenin g meth od employed by Lin in isola tin g th e EPO gene an d th e exten sive effort r equired to employ that meth od made the in ven tion n on obvious over the prior art. FN3 FN3. We n ote that both the district court and the parties have focused on the obviousness of a process for making the EPO gen e, despite the fact that it is products (gen es an d h ost cells) that are claimed in th e patent, n ot processes. We have directed our attention accordin gly, an d do not consider independen tly wh eth er th e products would

Page 9

have been obvious aside from the alleged obviousness of a method of making th em. Obviousn ess under Section 103 is a question of law. Panduit Corp. v. Dennison Mfg. Co., 810 F. 2d 1561, 1568, 1 USPQ2d 1593, 1597 (Fed.Cir.), cert. denied, 481 U.S. 105 2, 107 S.Ct. 2187, 95 L. Ed.2d 843 (1987). Th e district court stated that on e must in quire whether th e prior art would h ave suggested to on e of ordinary skill in th e art that Lin's probing an d scr een in g meth od sh ould be carried out and would have a reasonable expectation of success, viewed in light of th e prior art. See In re Dow Chemical Co., 837 F.2d 469, 473, 5 USPQ2d 1529, 1531 (Fed.Cir.1988). " Both th e suggestion and th e expectation of success must be foun ded in th e prior ar t, not in applicant's disclosure. " Id. Th e district court specifically found that, as of 1983, n on e of th e prior art references " suggest[s] that th e probin g strategy of usin g two fully-redun dant [sic] sets of probes, of relatively h igh degen eracy [sic], to scr een a h um an gen omic library would be likely to succeed in pullin g out th e gen e of in terest." FN4 13 USP Q2d at 1768. While *1208 it foun d that defen dants had sh own th at th ese pr ocedures were " obvious t o try," th e refer ences did n ot sh ow th at th er e was a reasonable expectation of success. See In re O'Farrell, 853 F.2d 894, 903-04, 7 USPQ2d 1673, 1680-81 (Fed.Cir. 1988). FN4. At this point, some explanation of th e in volved tech n olog y may be useful, con sistent with that expr essed in th e district court opinion. DNA con sists of two complemen tary strands of nucleotides, which in clude th e four basic compoun ds adenin e(A), guanin e(G), cytosin e(C), an d th ymine(T), orien ted so th at bases from on e stran d weakly bond to th e bases of th e oppo site stran d. A bon ds with T, and G bon ds with C to form complemen tary base pair s. This bondin g process is called hybridization an d results in the for mation of a stable duplex m olecule. Th e structure also in cludes 5-carbon sugar moieties with ph osphate groups. Th e gen etic code for a particular protein depen ds upon sequen tial gr oupin gs of three nucleotides, called cod on s. Each codon cod es for a particular amino acid. Sin ce th ere are four n ucleotide bases and three bases p er cod on , th ere are 64 (4x4x4 )

© 2007 Thomson/West. No Claim to Orig. U.S. Govt. Works.

Case 1:05-cv-12237-WGY

Document 821-5

Filed 08/16/2007

Page 10 of 19

927 F. 2d 1200 927 F. 2d 1200, 59 USLW 2575, 18 U.S.P.Q.2d 1016 (Cite as: 927 F.2d 1200) possible codon s. Because there are only 20 natural amin o acids, most amin o acids are specifi ed by mor e than one cod on. Th is is referr ed to as a " redun dan cy" or " degeneracy" in the gen etic code, a fact that complicates an d ren ders more difficult th e techn iques of recom bin ant DNA. In or der to pr epare a protein usin g recombin ant DNA techn olog y, th e gene for the pr otein must first be isolated from a cell's total DNA by screen in g a library of that cell's DNA. The DNA library is screen ed by use of a probe, a syn th etic radiolabelled n ucleic acid sequen ce which can be used to detect an d isolate complemen tary base sequen ces by h ybridization . T o design a pr obe wh en the gen e h as not yet been isolated, a scientist must kn ow th e amino acid sequen ce, or a portion th ereof, of the protein of interest. Because some amino acids have several possible codon s an d th e research er cannot kn ow wh ich of th e possible codon s will actually cod e for an amin o acid, h e or she may decide to design a set of probes that cover s all possible cod on s for each amin o acid compr ising th e protein, known as a " full y-degen erate" set of probes. A library to be screen ed can be a gen omic libr ary (gDNA), wh ich con tain s a set of all th e DNA sequences foun d in an organism's cells or a complementar y DNA (cDNA) library, wh ich is much smaller an d less complex than a gDNA library, and is used frequently wh en th e tissue source for a given gen e is kn own. [5] Defendants ch allenge the district court's determination, arguing th at, as of September 1983, on e of ordin ary skill in th e ar t would h ave h ad a reasonable expectation of success in screening a gDNA library by Lin 's method in order to obtain EPO. We agree with the district court's conclusion , wh ich was supp orted by convin cin g testimony. On e witn ess, Dr. Davies of Biogen , another biotechn olog y compan y th at had worked on E PO, stated th at he could not say wheth er Biogen scientists would h ave succeeded in isolating the E PO gen e if Biogen had th e EPO fragments that were available to Lin in 1983. Dr. Wall, a pr ofessor at UCLA, testified that it would have been " difficult" to fin d th e gen e in 1983, and that th ere would h ave been n o more than a fifty p ercen t chan ce of su ccess. He said, " you

Page 10

couldn 't be certain wh ere in th e genomic DNA your probe might fall." Th e court found th at n o on e had successfull y scr een ed a gen omic library using fullydegen erate probes of such high redundan cy as th e probes used by Lin. In th e face of th is and oth er eviden ce on both sides of th e issue, it con cluded that defen dants had n ot shown by clear an d convin cin g eviden ce th at the pr ocedures used by Lin would h ave been obvious in September 1983. We are n ot persuaded that the court erred in its decision. Defendants assert th at wh eth er or n ot it would have been obvi ous to isolate th e h uman EPO gene from a gDNA library with fully-deg enerate probes is immaterial because it was obvious to use th e already kn own mon key E PO gen e as a probe. Defen dants poin t out that, in th e early 1980s, Biogen did significan t work with an E PO cDNA obtained from a baboon , and that th ey used it as a probe to h ybridize with the correspon ding gene in a human gDNA library. However, this technique did n ot succeed un til after Lin isolated th e E PO gene with his fullydegen erate set of probes. T o support its obviousn ess assertion, defen dants rely upon th e testimon y of th eir expert, Dr. Flavell, wh o testified that th e overall homolog y of baboon DNA an d h uman DNA was " rough ly 90 percen t" . While th is testimon y in dicates th at it might have been feasible, perh aps obvi ous to try, to su ccessfully probe a human gDNA library with a mon key cDNA probe, it does n ot in dicate th at th e gene could h ave been identified an d isolated with a reasonable likelih ood of success. Neith er the DNA nucleotide sequen ce of th e h uman EPO gene n or its exact degree of h omolog y with *1209 the mon key EPO gen e was known at th e time. Indeed, th e district court found th at Lin was un successful at probin g a human gDNA library with m on key cDNA until after he had isolated th e E PO gen e by using the fully-degen erate probes. Based on th e eviden ce in the record, th e district court foun d th er e was n o r easonable expectation of success in obtaining th e E PO gene by th e method that Lin even tually used. Wh ile the idea of usin g th e monkey gen e to probe for a h omologous h uman gene may have been obvious to try, th e realization of th at idea would not have been obvious. Th ere were man y pitfalls. Hindsight is n ot a justifiable basis on wh ich to fin d that ultimate achievement of a lon g sought an d difficult scien tific goal was obvious. T h e district court th oroughly examin ed th e eviden ce and th e

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Case 1:05-cv-12237-WGY

Document 821-5

Filed 08/16/2007

Page 11 of 19

927 F. 2d 1200 927 F. 2d 1200, 59 USLW 2575, 18 U.S.P.Q.2d 1016 (Cite as: 927 F.2d 1200) testimon y. W e see n o error in its result. Moreover, if th e DNA sequence was n ot obvi ous, h ost cells con tainin g such sequen ce, as claimed in claim s 4 an d 6, could n ot have been obvious. We conclude that the district court did not err in h olding that th e claims of th e patent are n ot invalid under Section 103. C. B est Mode Defen dants argue th at th e district court erred in failin g to h old the '008 paten t invalid under 35 U. S.C. § 112, assertin g that Lin failed to disclose th e best mammalian host cells kn own to him as of November 30, 1984, the date h e filed h is fourth paten t application . [6] Th e district court foun d that th e " best mode" of practicing th e cla imed inven tion was by use of a specific gen etically-heter ogen eous strain of Ch in ese hamster ovary (CHO) cells, wh ich produced EPO at a rate greater than that of other cells. It furth er foun d th at th is strain was disclosed in E xample 10 an d that Lin knew of n o better mode. GI argues th at Lin's best mode was not adequately disclosed in Example 10 because one skilled in th e art could n ot duplicate Lin's best mode without his havin g fir st deposited a sample of th e specific cells in a public depository. The issue before us th erefore is wheth er the district court erred in concludin g th at Example 10 of the '008 paten t satisfied th e best mode r equirement as to th e in ven tion of th e challenged cla ims FN5 an d that a deposit of the preferred CHO cells was n ot n ecessar y. FN5. Defen dants assert that all th e claims sh ould be invalid for failure to disclose th e best mode. W e perceive that th e best m ode issue on ly relates to th e h ost cell claims, 4, 6, 23-27, and 29. Absent inequitable con duct, a best mode defen se on ly affects those claim s coverin g subject matter the practice of which has n ot been disclosed in complian ce with th e best mode requirement. See Northern Telecom, Inc. v. Datapoint Corp., 908 F. 2d 931, 940, 15 USPQ2d 1321, 1328 (Fed.Cir.), cert. denied, 498 U. S. 920, 111 S. Ct. 296, 112 L.Ed.2d 250 (1990). A determination wh eth er th e best mode requiremen t is satisfied is a question of fact, DeGeorge v. Bernier, 768 F.2d 1318, 132 4, 226 USPQ 758, 763 (Fed.Cir.1985); we th erefore review the district court's fin din g un der a clearly err oneous stan dard.

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35 U.S.C. § 112 provides in relevan t part: Th e specification shall con tain a written description of the invention, an d of th e m ann er an d process of making and usin g it, in such full, clear, concise, an d exact terms as to en able an y person skilled in the art to wh ich it pertains, or with wh ich it is most n early con n ected, to make an d use th e same, and shall set forth the best mode contemplated by the inventor of carrying out his invention. (Emphasis added). [7][8] This court has recently discussed the best m ode requiremen t, poin ting out that its analysis h as two componen ts. Chemcast Corp. v. A rco Indus. Co rp., 913 F.2d 923, 927 , 16 USPQ2d 1033, 1036 (Fed.Cir.1990). The first is a subjective on e, askin g whether, at the time th e in ventor filed h is paten t application, he contemplated a best mode of practicin g his inven tion . If h e did, the secon d in quiry is wh eth er his disclosure is adequate to en able on e skilled in th e art to practice the best mode or, in other words, wh ether the best mode h as been con cealed from th e public. Th e best mode requir ement th us is in tended to ensure that a patent applican t *1210 plays " fair and square" with the paten t system. It is a r equirement that the quid pro quo of th e patent grant be satisfied. On e must not receive the righ t to exclude others unless at th e time of filin g h e h as provided an adequate disclosure of th e best mode kn own to him of carryin g out h is in vention. Our case law h as in terpreted th e best mode requirement to mean that th er e must be no concealm ent of a mode kn own b y th e in ven tor to be better than that wh ich is disclosed. Hybritech Inc. v. Monoclonal A ntibodies, Inc., 802 F.2d 1367, 1384-85, 231 USPQ 81, 94 (Fed.Cir.1986), cert. denied, 480 U.S. 947, 107 S.Ct. 1606, 94 L.Ed. 2d 792 (1987). Section 282 imposes on those attemptin g to prove in validity the burden of proof. We agree th at the district court did n ot err in fin ding that defendan ts h ave not met th eir burden of provin g a best mode violation. As n oted above, the district court found that th e best m ode of making the CHO cells was set forth in E xample 10. As th e district court stated, wh ile it was n ot clear wh ich of two possible strains Lin con sidered to be th e best, the cell strain subjected to 1000 nanomolar MTX (methotrexate) or that subjected to 100 nan omolar MT X, the best mode was disclosed because both were disclosed. FN6 Defendants argue that th is disclosur e is n ot enough,

© 2007 Thomson/West. No Claim to Orig. U.S. Govt. Works.

Case 1:05-cv-12237-WGY

Document 821-5

Filed 08/16/2007

Page 12 of 19

927 F. 2d 1200 927 F. 2d 1200, 59 USLW 2575, 18 U.S.P.Q.2d 1016 (Cite as: 927 F.2d 1200) th at a deposit of the cells was required. FN6. In its opin ion, th e district court stated that " the best wa y to express EPO was from mammalian cells ... and that a cell line derived from 11 possible clon es from th e CHO B11 3,. 1 cell strain was to be used for Amgen's master wor king cell bank, which was exp ected to be sta rted on November 26, 1984." 13 USPQ2d at 1772. At an other poin t, th e court stated th at Amgen " did disclose the best mode in Example 10 of the inven tion , wh en it described the production rates of th e 100 nanomolar-amplified cells (the B11 3,.1 cell strain ) and on e micr omolar -treated cells." Id. Defen dants con ten d that " [i]n th e field of livin g materials such as microorganisms an d cell cultures," we sh ould require a biological deposit so that the public has access to exactly th e best mode con templated by th e in ventor. Th is presen ts us with a question of first impression concern in g the best mode requirement for paten ts involvin g novel gen eticallyen gin eer ed biological subject matter. For man y years, it has been customary for paten t applican ts to pla ce microorganism samples in a public depositor y wh en such a sample is n ecessary to carry out a claimed in vention . This practice ar ose out of th e devel opmen t of an tibiotics, wh en micr oorgan isms obtain ed from soil samples uniquely syn th esized an tibiotics wh ich could n ot be readily prepared ch emically or otherwise. In re Argou delis, 434 F.2d 1390, 168 USPQ 99 (CCPA 1970). Such a deposit has been con sidered adequate to satisfy th e enablement requirement of 35 U.S.C. § 112, wh en a written description alon e would n ot place the in ven tion in the hands of the public and ph ysical possession of a unique biological material is required. See, e.g., In re Wands, 858 F.2d 731, 735-36, 8 USP Q2d 1400, 1403 (Fed.Cir.1988) (" Wh ere an in ven tion depen ds on th e use of living materials ... it may be impossible to en able th e public to make the in ven tion (i.e., to obtain these living materials) solely by means of written disclosure." ); In re Lundak, 773 F.2d 1216, 1220, 227 USPQ 90, 93 (Fed. Cir. 1985) (" When an invention relates to a n ew biol ogical material, the material may n ot be reproducible even wh en detailed procedures an d a complete taxonomic description are in cluded in th e specification." ); see generally Hampar, Patenting of Recombinant DNA Technology: The Deposit Requirement, 67 J. Pat. &

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Trademark Off. S oc' y 569, 607 (1985) (" Th e deposit r equirement is a n on statutory mech an ism for en suring complian ce with the ` enablin g' provision und er 35 U. S. C. § 112. " ). Th e district court foun d th at th e claims at issue r equire th e use of biological materials th at were capable of bein g prepared in th e laboratory from r eadily availa ble biological cells, usin g th e description in Example 10. Th e court also foun d that th er e were n o starting mater ials that were n ot publicl y available, that were not described, or that r equired un due experimen tation for th eir preparation in or der to carry out th e best mode. T he court n oted th at Lin testified *1211 th at th e isolation of th e preferred strain was a " routin e limited dilution cloning procedure[ ]" well known in th e ar t. Dr. Simon sen , GI's own expert, testified that th e disclosed procedures were " stan dard" and that: with the vectors and th e sequences shown in Example 10, I h ave no doubt that someon e even tually could r eproduce-well, could gen erate cell lin es [sic, strains] making some level of EPO, and they could be better, th ey could be worse in terms of EPO production . Th e district court relied on this testimony, and, upon r eview, we agree with its determination. Th e testimon y accurately reflects that th e in vention , as it r elates to th e best mode h ost cells, could be practiced by on e skilled in th e art followin g Example 10. Thus, th e best mode was disclosed an d it was adequately en abled. [9] Th ese mater ials ar e th erefore n ot analogous to th e biol ogical cells obtained from un ique soil samples. Wh en a biological sample required for the practice of an in vention is obtained from n ature, the in ven tion may be in capable of bein g practiced without access to that organ ism. Hence the deposit is required in that case. On the other h and, wh en, as is the case h ere, the organism is cr eated by in sertion of genetic material in to a cell obtained fr om gen erally availa ble sour ces, th en all that is required is a description of th e best m ode and an adequate descr iption of th e mean s of carr ying out th e in ven tion, n ot deposit of the cells. If th e cells can be prepared with out undue experimentation from known materials, based on th e description in the paten t specification , a deposit is n ot r equired. See Feldman v. A unstrup, 517 F.2d 1351, 1354, 186 USPQ 108, 111 (CCPA 1975), (" No problem exists wh en the microorganisms used are kn own and readily available to th e public." ), cert. denied, 424 U. S. 912, 96 S. Ct. 1109, 47 L.E d.2d 316

© 2007 Thomson/West. No Claim to Orig. U.S. Govt. Works.

Case 1:05-cv-12237-WGY

Document 821-5

Filed 08/16/2007

Page 13 of 19

927 F. 2d 1200 927 F. 2d 1200, 59 USLW 2575, 18 U.S.P.Q.2d 1016 (Cite as: 927 F.2d 1200) (1976). Since th e court foun d that that is th e case h ere, we th erefore hold th at th ere is n o failure to comply with th e best mode requirement for lack of a deposit of the CHO cells, wh en th e best mode of preparin g th e cells has been disclosed an d th e best mode cells h ave been enabled, i.e., th ey can be prepared by on e skilled in th e art from kn own materials using the descr iption in th e specification. Defen dants also con ten d that the examin er's rejection of the application that matured into the '008 paten t for failure to make a publicly accessible biol ogical deposit supports its argument. U. S. Paten t Application Serial No. 675, 298, Prosecution Histor y at 179 (First Rejection July 3, 1986). However, that rejection was with drawn after an oral interview and a written argument that the in vention did n ot r equire a deposit. Id. at 208. We also note th at the PTO has recently prescribed guidelin es concern in g th e deposit of biol ogical materials. See 37 C. F. R. § 1.802(b) (1990) (biological material n eed n ot be d eposited " if it is kn own and readily available to the public or can be made or isolated without un due experimen tation" ). The PT O, in response to a question as to whether th e deposit requirement is applicable to the best m ode requirement, as distin ct from enablemen t, said: The best mode requir ement is a safeguard against th e possible selfish desire on th e part of some people to obtain paten t protection without makin g a full disclosure. Th e requirement does n ot permit an in ven tor to disclose on ly wh at is known to be the second-best embodim ent, r etain ing the best.. .. Th e fun damental issue that sh ould be addressed is wh eth er there was eviden ce to sh ow th at the quality of an applicant's best mode discl osure is so p oor as to effectivel y result in concealment. In re Sherwood, 615 [613] F.2d 809, 204 USPQ 537 (CCPA 1980). If a deposit is th e on ly wa y to com ply with th e best mode requirement then the deposit must be made. 52 Fed.Reg. 34080, 34086 (Sept. 8, 1987). FN7 FN7. See also 53 Fed.Reg. 39420, 3942 5 (Oct. 6, 1989) (comment re " deposit [to] satisfy the best mode requirement" ); 52 Fed. Reg. 34080, 34080 an d 34084 (Sept. 8, 1987) (deposit may be required to satisfy en ablement, best mode, or distinct claim requirements of § 112). We see no incon sisten cy between th e district cour t's

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decision, which we affirm h ere, and these guidelines. *1212 Defen dan ts also assert that the r ecord sh ows th at scientists were unable to duplicate Lin's gen etically-heterogen eous best mode cell strain. However, we have lon g held that the issue is whether th e disclosure is " adequate," n ot th at an exact dup lication is n ecessary. Indeed, th e district court stated that [t]h e testimon y is clear that n o scientist could ever dup licate exactly th e best mode used by Amgen, but th at th ose of ordinary skill in th e art could produce m am malian h ost cell strains or lin es with similar levels of production iden tified in Example 10. 13 USPQ2d at 1774. What is required is an adequate disclosure of th e best mod e, not a guarantee that ever y aspect of th e specification be precisely an d universally reproducible. See In re Gay, 309 F.2d 769 , 773, 135 USPQ 311, 316, 50 CCPA 725 (1962). Defendants finally argue that Lin's failure to deposit th e tran sfected cells n otwith stan ding the fact th at h e was willin g to deposit essentially worth less cell m aterial was evidence of deliberate con cealm ent. We have already stated th at deposit of the h ost cells con tainin g the rEPO gen e was not n ecessar y to satisfy th e best mode requirement of Section 112. Th e best mode was disclosed an d a deposit was n ot n ecessary to carry it out. Th erefore, th e fact that some cells wer e deposited, but n ot oth ers, is irrelevant. D. Enablement of claims 7, 8, 23-27, and 29 Amgen argues that th e distr ict court's h olding that GI " provided clear an d con vincing evidence th at th e paten t specification is in sufficien t to enable on e of ordinary skill in th e art to make an d use the inven tion claim ed in claim 7 of the '008 paten t with out undue experimentation" con stituted legal error. 13 USPQ2d at 1776. Amgen specifically argues that th e district court erred because it " did n ot properly address th e factors wh ich th is court has h eld must be con sidered in determinin g lack of en ablemen t based on asser tion of un due experimentation," citing this court's decision in In re Wands, 858 F.2d at 737, 8 USPQ2d at 1404. Claim 7 is a generic claim, covering all possible DNA sequen ces that will en code an y polyp eptide having an amin o acid sequen ce " su fficiently dup licative" of EPO to possess the property of in cr easing production of red blood cells. As claims 8,

© 2007 Thomson/West. No Claim to Orig. U.S. Govt. Works.

Case 1:05-cv-12237-WGY

Document 821-5

Filed 08/16/2007

Page 14 of 19

927 F. 2d 1200 927 F. 2d 1200, 59 USLW 2575, 18 U.S.P.Q.2d 1016 (Cite as: 927 F.2d 1200) 23-27, and 29, depen den t on claim 7, are not separately argued, and are of similar scope, th ey stan d or fall with claim 7. See In re Dillon, 919 F.2d 688, 692, 16 USPQ2d 1897, 1900 (Fed. Cir. 1990) (in banc). [10] Wh eth er a claimed invention is enabled un der 35 U. S. C. § 112 is a question of law, wh ich we review de novo. Moleculon Research Corp. v. CBS, Inc., 793 F.2d 1261, 1268, 229 USPQ 805, 811 (Fed.Cir. 1986), cert. denie d, 479 U.S. 1030, 107 S. Ct. 875, 93 L.E d.2d 829 (1987). " To be en ablin g un der § 112, a paten t must contain a description that enables on e skilled in the art to make and use th e claim ed in ven tion ." A tlas Powder Co. v. E. I. duPont De Nemours & Co., 750 F. 2d 1569, 1576, 224 USPQ 409, 413 (Fed. Cir.1984). [11] That some experimen tation is n ecessary d oes not con stitute a lack of en ablement; the amount of exper imentation, h owever, must n ot be un duly exten sive. Id. Th e essential question h ere is whether th e scope of en ablement of claim 7 is as br oad as the scope of the claim. See generally In re Fisher, 427 F.2d 833, 166 USPQ 18 (CCPA 1970); 2 D. Chisum, Patents § 7.03[7][b] (1990). The specification of th e '008 paten t provides that: on e may readily design and manufacture genes codin g for microbial expression of p olypeptides having primary conformations which differ from that h erein specified for mature E PO in terms of the identity or location of on e or more residues (e.g., substitutions, terminal an d intermediate addition s an d deletion s). ****** DNA sequ en ces provided by th e presen t in vention are th us seen to compr eh en d all DNA sequen ces suitable for use in securin g expression in a procaryotic*1213 or eucaryotic host cell of a polypeptide product h aving at least a part of th e primary structural conformation and on e or more of th e biological properties of er ythropoietin , an d selected from amon g: (a) th e DNA sequen ces set out in FIGS. 5 an d 6; (b) DNA sequ ences which h ybr idize to the DNA sequen ces defin ed in (a) or fragments th ereof; an d (c) DNA sequences wh ich , but for th e degeneracy of th e gen etic code, would h ybr idize to th e DNA sequences defin ed in (a) an d (b). The district court found that over 3,600 differen t EPO

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an alogs can be made by su bstituting at only a sin gle amino acid position, an d over a million different an alogs can be made by su bstituting three amin o acids. The patent in dicates that it embraces means for preparation of " n umer ous" polypeptide analogs of E PO. Thus, the n umber of claim ed DNA encodin g sequen ces that can produce an E PO-like product is poten tially en ormous. In a deposition, Dr. E lliott, wh o was h ead of Amgen 's EPO analog program, testified that h e did n ot kn ow whether th e fift y to eighty EPO analogs Amgen had made " had the biological property of causin g bon e m arrow cells to increase production of reticulocytes an d r ed blood cells, and to increase hemoglobin syn th esis or ir on uptake." Based on this evidence, th e trial cour t con cluded that " defendants had provided clear an d con vincing eviden ce that th e paten t specification is in sufficien t to enable on e of ordinary skill in th e art to make an d use the inven tion claim ed in claim 7 of the '008 paten t with out undue experimentation. " 13 USPQ at 1776. In making this determin ation , th e court relied in particular on th e la ck of predictability in th e art, as demon strated by th e testimon y of both Dr. Goldwasser, an oth er scientist wh o worked on procedures for purifyin g urinary EPO (uEPO), an d Dr. Elliott. After five years of experimentation, th e court n oted, " Amgen is still unable to specify wh ich an alogs have th e biological properties set forth in claim 7." Id. [12][13] We believe th e trial court arrived at th e correct decision, alth ough for th e wron g reason. By focusin g on th e biological properties of th e E PO an alogs, it failed to consider th e en ablemen t of th e DNA sequen ce an alogs, wh ich are th e subject of claim 7. Moreover, it is not n ecessary th at a patent applican t test all the embodim ents of h is in vention, In re Angstadt, 537 F. 2d 498, 502, 190 USPQ 214, 218 (CCPA 197 6); what is n ecessary is that h e provide a disclosure sufficien t to en able one skilled in th e art to carr y out th e in vention commen surate with the scope of his claims. For DNA sequen ces, that mean s disclosin g how to make an d use en ough sequen ces to justify grant of the claims sought. Amgen has n ot don e that h ere. In addition, it is n ot n ecessary that a court review all the Wands factors to find a disclosure en abling. Th ey are illustrative, n ot man datory. What is relevan t depen ds on th e facts, and the facts h ere are th at Amgen has n ot enabled preparation of DNA sequen ces su fficien t to support its all-encompassin g claim s.

© 2007 Thomson/West. No Claim to Orig. U.S. Govt. Works.

Case 1:05-cv-12237-WGY

Document 821-5

Filed 08/16/2007

Page 15 of 19

927 F. 2d 1200 927 F. 2d 1200, 59 USLW 2575, 18 U.S.P.Q.2d 1016 (Cite as: 927 F.2d 1200) [14] It is well establish ed that a patent applican t is en titled to claim his inven tion generically, wh en h e describes it sufficien tly to meet th e r equirements of S