*1 CONCLUSION (Fed.Cir.1994)). rea Our 394, 400 F.3d pres to the inapposite is soning SciMed reasons, we vacate For above-stated SciMed, using specifi case. ent summary judg- grant of district court’s way claim in to define cation of Dis- in favor non-infringement of ment matter, subject certain clearly excluded proceedings for further and remand ney matter subject disclaimed patentee opinion. consistent asserting thereby barred was and REMANDED. AND VACATED equiva of the doctrine under infringement case, paten In this Id. at 1346. lents. COSTS explicitly dis implicitly has tee costs. No by using the subject matter any claimed locator” resource “uniform expression construed. correctly is
Therefore, application conclude we not barred equivalents doctrine reason. for that
simply B and CORPORATION GENZYME analyses of insub Although Medicine Mount Sinai School similar, a court are difference stantial University, Plaintiffs-Ap- York New infringement separate conduct must pellants, equivalents the doctrine of analysis under in of literal analysis conducting after THERAPIES, TRANSKARYOTIC written for claim limitations
fringement INC., Defendant-Appellee. literal format if both means-plus-function under infringement infringement No. 02-1312. Apex are asserted. equivalents doctrine Appeals, Court United States Inc., F.3d Computer, v. Raritan
Inc. Federal Circuit. limita (Fed.Cir.2003). For form, means-plus-function written in tion 9, 2003. Oct. concerning equiv arguments
evidence ¶ substantially may § under
alents the doctrine concerning those
overlap with However, evidence equivalents. “types” concerning two
arguments analyses, respective their
equivalents, coextensive. perfectly by no
are means Sales,
See, e.g., Kemco
1364-65. remand, should the district court
On literal in- allegations ACTV’s
entertain under infringement
fringement with this equivalents, consistent
doctrine court. of this precedents
opinion and the *2 Coruzzi,
Laura A. Pennie & Edmonds LLP, York, NY, New argued plain- for tiffs-appellants. With her on the brief Rabinowitz; Stephen were S. and Stanton Lawrence, T. III and Wagner, Todd A. a- producing A method LLP, Washington, Edmonds, Pennie & comprising: galactosidase DC. contain- (a) mammalian cell culturing a Rogers Ben-Ami, Chance Clifford Leora nu- chromosomally integrated ing a York, NY, argued LLP, of New & Wells *3 a- human encoding sequence cleotide her on With defendant-appellee. for reg- by a A controlled galactosidase and Vladimir A. Carson Patricia were brief ulatory promotes that sequence Drozdoff. and a selectable gene expression or by same marker controlled LINN, SCHALL, RADER, Before so sequence, regulatory different Judges. Circuit A nucleotide a-galactosidase stably overexpressed is sequence by Circuit court filed Opinion a-galac- active enzymatically an concurring-in- Opinion Judge RADER. by the secreted enzyme A is tosidase by Circuit filed dissenting-in-part part and cell; and mammalian Judge LINN. a-ga- (b) enzymatically active isolating mam- enzyme from the RADER, Judge. lactosidase A Circuit cell culture. malian for the District Court States The United comprising a mammalian cell A10. on sum- determined Delaware District chromosomally integrated nucleo- Transkaryotic Thera- mary judgment human a- encoding sequence tide (TKT) infringe Genzyme did not pies, Inc. reg- by a A controlled galactosidase School Sinai and Mount Corporation’s sequence ulatory promotes Genzyme) patent (collectively, Medicine’s and a selectable gene the human en- producing on methods or by the same marker controlled Genzyme Because A. zyme agalactosidase so regulatory sequence, different properly infringement cannot prove A nucleo- a-galactosidase claims, affirms. this court construed stably overex- is tide active enzymatically an pressed and I. enzyme is secret- A ¥-galaetosidase cell. ed the mammalian the exclusive is Genzyme Corporation (the 5,356,804 Patent No. of U.S. licensee TKT, alleging Genzyme against filed suit 1994, issued October patent), '804 TKT’s patent. '804 infringement School Mount Sinai its face assigned on infringing product involves allegedly University. The of New York of Medicine Un- gene activation. technique known as producing claims a method sequence acting a DNA technique, der this (a-Gal-A) and A a-galactosidase human into a human inserted promoter is as a and secrete express engineered cells hu- cell, endogenous whereupon host Administration a-Gal-A. active human A encoding is gene a-Gal cellular man patients suffer- treats protein A a-Gal hu- express activated disease, trig- a condition Fabry ing from undisputed It A is protein. a-Gal man enzyme. deficiency gered by not introduce technique does that TKT’s appeal are in this at issue The claims cells. and 10 of the '804 1 independent claims independent construed district court (emphases follows read
patent, which
in a
the '804
1 and
added):
hearing.
Markman
See
mosomally
Markman
integrated,” Genzyme conceded
Instruments,
Westview
these disputed important most decision, court’s arguing that the district “chromosomally integrated,” court in defining erred the claim terms district court defined to mean “the combin “chromosomally integrated,” “regulatory bringing together merging sequence,” “stably,” “comprising.” elements,” separate specifically the “chro This court has *4 jurisdiction exclusive to a mosome of host cell” “an exogenous Genzyme’s hear appeal. 28 U.S.C. sequence encoding nucleotide a- human 1295(a)(1)(2000). § galaetosidase A promoter awith and se lectable marker.” Genzyme v. Corp. II. Inc., Transkaryotic Therapies, No. 00- Claim construction is a matter of
677-GMS, (D.Del. 1530375, 2001 WL at *1 law, which this court reviews without deference. 2001) Nov.28, Cy Techs., Corp. Inc., v. FAS bor Following the Markman proceedings, 1448, 138 (Fed.Cir.1998) (en F.3d 1456 both Genzyme banc). and TKT moved for sum- This court also grants reviews mary judgment on infringement. In its summary judgment without deference. summary judgment motion for nonin- Johns Hopkins Univ. v. Cellpro, 152 fringement, TKT explained that it pro- 1342, 1353(Fed.Cir.1998). F.3d duces human A genetical- ot-Gal from cells “Chromosomally Integrated” ly engineered overproduce to enzyme this gene gene via activation. TKT’s activation dispute in case on turns process permits controlled the meaning of “chromosomally integrat endogenous human target a-Gal A in cells. Essentially, ed.” does the term “chromo argued TKT it practice does not somally integrated” require the action of claimed method because the “chromosom- inserting a human a A gene into the host ally integrated” requires limitation exoge- chromosome, TKT, as argued by can it nously introduced gene sequences, step a cover a gene technique activation in which gene protocol activation uti- does not only a promoter sequence inserted into a lize. human cell in order to the a activate cell, A already present in the host fifing A week after its motion for sum- argued Genzyme. mary judgment infringement, Genzyme asked the district clarify court its inter- The district court construed “chromo- pretation of the claim term somally “chromosomal- integrated” to mean “the combin ly integrated,” particularly respect with to ing or bringing together merging meaning of the phrase “exogenous nu- separate elements.” Further the district cleotide.” The complied district court with case, court “In reasoned: the separate Genzyme’s request, stating that the term elements that are combined are the chro “exogenous” referred se- mosome exogenous nucleotide the host cell an quences “exogenous cell, to the host sequence encoding nucleotide human a- to the chromosomal site.” galactosidase A a promoter and se Based on this meaning of term “chro- lectable marker.” 2001 Genzyme, WL
1098 added). 299 Corp., v. N. Am. F.3d flex, Inc. Ficosa
1530375, (emphasis Gen at *1 (Fed.Cir.2002)). In other 1325-26 specify the claims do argues that zyme words, consistently patent applicant may to be origin of nucleotide clearly in a term a manner either use cell’s chromosome. target into a inserted general expansive more or than its less “chromo- term According Genzyme, community, and thus usage the relevant that “a requires only integrated” somally term in or limit the expand contain cell must chromosome claims. Ballard the context of the that encodes nucleotide Allegiance Healthcare Med. Prods. words, enzyme.” In other Gen- A ¥-Gal (Fed.Cir.2001) Corp., F.3d “requires claim term argues, this zyme disclaim (noting applicant may that an be located coding sequence A ¥-Gal scope during prosecution); Middle chromosome,” of whether regardless Co., ton, Mining Mfg. Inc. v. & Minn. within the sequence originated coding (Fed.Cir.2002) (explaining F.3d Thus, as Genzyme the cell. or outside scope, disavow claim order to impermissibly court district serts applicant clearly must and unam preferred embodi limited the claim to subject biguously surrender of express coding integrating *5 ment during In ascertain prosecution). matter exoge host cell an a from usage of the relevant accustomed nous source. time, community the relevant dictionar at expressly does not patent may inform ies and treatises serve to Rath “chromosomally integrated.” define Sys., Telege Digital courts. Tex. Inc. court, court, must er, (Fed.Cir. like district 1193, nix, F.3d 1202-03 308 of the from its meaning derive the term 2002). princi A fundamental usage context. alone, Standing “chromosom words usage a is the discerning term’s ple for integrated” suggest uniting sepa two ally ordinary meaning and accustomed to form portions genetic rate material a amongst ordinary skill in artisans
words complete purposeful more whole. To at the of invention. the relevant art time biology, one skilled in the art molecular Corp., Corp. v. Laitram 274 See Rexnord “integration” generally means “insertion (Fed.Cir.2001). Indeed, 1336, F.3d 1342 a DNA sequence] genome into a host [of “heavy usage rules a suggest normal region covalently a linked side on either their carry claim presumption” that terms Lewin, Benjamin host sequences.” com meaning accustomed relevant (1990). Thus, IV 812 lan Genes Fitness, at the time. munity relevant CCS suggests incorporation exogenous guage 1359, Corp., Inc. v. Brunswick genetic into the chromosomal materi code (Fed.Cir.2002) (citing Johnson 1366 context, al of the cell. In the asserted 175 Corp., Inc. v. Zebco Worldwide Assocs. explain exogenous that se course, 985, (Fed.Cir.1999)). F.3d Of quence regulatory sequence a has acknowledged a patent law has stably overexpress causes the host cell to applicant may presumption overcome this A. then ¥-Gal The cell secretes excess clearly words in the using specifica “integrated” sug ¥-Gal A. the word Again tion, history, “in exogenous or both nucleotide gests putting se ordinary manner inconsistent with its quences into the host cell’s chromosome to word, Boehringer Ingelheim meaning.” process. Vetmed facilitate this This howev er, ica, conclusively Schering-Plough Corp., Inc. v. does evince whether 1339, 1347(Fed.Cir.2003) Tele- one of skill in the art at time of (citing F.3d invention would understand the exogenous that viruses lack a cellular structure of sequences to come from own, outside the host their and must infect a “host cell” to cell, i.e., vector, within the host effect replication); see also Bernard R. cell but outside chromosome, the critical Glick and Jack Pasternak, J. Biotechnolo- i.e., a transposable (2003) gy element. this re- (defining a “host” to be “[a] gard, perhaps the best put microorganism, tool to organism, or cell claims in proper temporal and maintains a vector)”; technical cloning Chambers context is the patent Dictionary specification itself. Science and Technology 570 (Peter Walker, 1999) ed., M.B. (defining a Throughout the '804 patent specifica- “host” as meaning “in biology molecular tion, the applicant consistently uses the that in which plasmid or virus can repli- term “integrated” refer to a foreign cate”). Thus, the invention involves “clon- gene inserted into a host cell chromosome. ing and expressing the a-Gal A coding See, e.g., 14, col. 11.14-19 sequence in eukaryotic host (stable integration plasmid DNA into systems,” explanation one of skill in the chromosomes); 24, host cell col. 11.42-46 art would read as introducing exogenous (transfection of human sequences into Af- cloned sequences into a host cell for ex- green (COS) rican monkey cells); kidney pression. This definition of the invention (transfection col. 11. 60-64 of human does not embrace targeting or activation of sequences into Chinese Ovary Hamster an endogenous gene. (CHO) cells); col. (amplification 1-2 In reading integrated specification plasmid cells); DNA CHO teach “ehromosomally integrated” and col. 11.59-66 means intro- (transcription of sta- ducing genetic bly material integrated cells). vector DNA CHO *6 cell, just host not Indeed, chromosome, the multitude of this court working exam- is aware that ples, various drawings, portions diagrams patent and of the '804 refer patent vaguely to using less show the than the full foreign insertion a- endogenous coding Gal-A coding sequence for sequences express- into host cells to 5.1, a-Gal A. In generate section expression excessive entitled “The of the pro- ¥-Gal SEQUENCE,” tein. A CODING the pat- ent recites: Notably, the “Summary of the Inven Although portions of the coding se- tion” explicitly states “present quences may utilized, be full length invention,” merely not a preferred embodi clones, i.e., those containing the entire ment, production “involves the of large coding region A, for may a-Gal pref- be quantities of human A by cloning a-Gal erable for expression. and expressing the A coding a-Gal se patent, 10, ll. ’804 61-63; also, col. see quence in col. eukaryotic expression host cell ll;. place, 51-52. the first this systems.” pas '804 patent, col. 11.22-30. sage does not expressly refer Likewise, to activation the abstract patent of the '804 endogenous genes at all. Rather in describes recovery in “good yield” of “re context, passage merely explains that combinant A” a-Gal from “engineered host less than the entire coding sequence may cells.” patent thus specifically uses be express used to a functional A “host a-Gal cells” to express large quantities of protein. ¥-Gal A. The term “host cell” means that
the cell or genetic “hosts” Indeed, “receives” mate this passage in explains context rial other than its own perform to its ser potential coding abbreviated se- Lewin, vice. See supra at 41 (explaining quence would come from outside the host etc.), sites, and nators, polyadenylation to proceeds Specifically, cell. The selectable marker. order a selectable “[i]n 5.2 that in section explain A, con- plasmid a-Gal in the recombinant active marker biologically express a func- enzyme, al- and for selection resistance coding fers sequence, a modified plasmid integrate the equivalent, stably tional cells to lows 5.1., in- supra, is in Section grow described and chromosomes their into eukaryotic ex- appropriate into serted cloned can be in turn foci which form contains vector, a vector i.e. pression (Emphasis cell lines. into expanded transcription for necessary elements added.) coding se- the inserted translation un- 11.4-19. col. patent, ’804 eukaryotic host appropriate in quence from column fragment sentence derlined 12, 11.35-42 at col. '804 cells.” context, suggest does 14, when read added). specifi- again, Once (emphasis coding targeting of gene exoge- introduction emphasizes cation cell. a host within possible cells. into host material nous genetic may cells Rather, host states passage fragment taken Similarly, one sentence (i.e. A” with the be “transformed 10-14, 14, lines column context in out of con- with “DNA entirety) or in its cell with transforming a host mentions control expression by appropriate trolled DNA, than the entire rather controllable As a selectable marker.” elements cells can “[H]ost sequence: A ¥-Gal above, the DNA type in bold noted DNA the a-Gal transformed introduced foreign 14 is DNA column con- expression by appropriate controlled teach- passage via vectors. cells host ...), (e.g. promoter trol elements viral containing expression vectors reference, es how- This marker.” selectable to facili- used replication are origins heading “Construction ever, falls under Instead, A. of a-Gal expression Preparation of stable tate Vectors Expression of recombinant the use section refers teaches This entire column Transfeetants.” a- con- “expression containing other plasmids a vector creating elements, cell.” and en- promoters such as [chosen] Gal A trol *7 also, 11-13; col. expres- see the hancers, continuously drive patent, col. preceding the sentence the Indeed 11.55-58. A DNA located of the a-Gal sion express- refers context of fragment the out produc- high-yield “long-term, for plasmids DNA,” foreign of “introduction ly to the '804 proteins.” of recombinant tion DNA: of targeting 14, II. 4-19. at col. of yield production high long-term, For in col- Therefore, fragment the sentence expression stable proteins, recombinant context, teaches read when umn following example, For is preferred. of into host cells introduction DNA, engi- foreign introduction A, pro- encoding together a-Gal DNA for grow bemay allowed cells neered plas- recombinant enhancers in moters media, and then days 1-2 an enriched suggest does This passage mids. Rather media. selective to a switched con- expression a cell introduction which con- vectors using expression than coding of a portion and a elements trol cells replication, origins tain viral genes expression to drive sequence A or a-Gal with the can transformed cell. the host located within endogenously expres- appropriate by DNA controlled in columns Thus, passages the isolated en- promoter, (e.g. control elements sion remotely suggest not even do termi- hancer, transcription sequences, “chromosomally integrated” target- means claimed vector. The examiner considered ing sequences encoding a-Gal A that the deposit “essential” to the in- claimed endogenous to a host are cell. vention. applicant conceded, The made the deposit without arguing against if, arguendo, Even passages the cited Thus, the requirement. during prosecu- example gene did teach an targeting, tion, applicant agreed that the pending gene targeting require such would still required claims a recombinant vector en- introduction of exogenous nucleotide se- coding Later, a-Gal A. the applicant quences encoding human a-Gal A. Gene amended the claims to remove the term targeting involves typically the transfec- vector,” “recombinant but neither the ex- of a containing gene tion vector aminer nor the applicant suggested that into a cell containing an endogenous form the amendment rendered the deposit un- transfection, the gene. Upon the exoge- Thus, necessary. prosecution history nous vector targets the endogenous gene, shows necessity deposited ex- homologous occurs, recombination and ex- ogenous vector pat- the '804 ogenous sequences part become of the ge- ent claims. nome.1 This process requires the intro- duction of at foreign gene least some DNA prosecution, During applicant also cell,
into the host and is not the same as arguments made to overcome prior art transposable elements rearranging genes that are inconsistent with a broad inter- a cell. within No record suggests evidence pretation of the claim term “chromosomal- specification that the contemplates, much ly integrated.” rejected The examiner defines, integration less expression claims §§ under 35 U.S.C. 102 and 103 in genes chromosome, outside a chosen but view of prior art that allegedly taught the within a cell via transposable elements. assembly vectors containing human a-Gal A sequences. history, like specifi- Specifically, cation, rejected permit does not examiner pending a broad interpreta- genomic over tion the claim term “the clone “chromosomally containing in- tegrated.” promoter original the human gene claims of a-Gal A recited by Quinn, a method of disclosed producing hu- or the a-GalA cDNAs protein man a-Gal A disclosed produc- Tsuji, Bishop, cells for Coppola or Cal- enzyme transformed houn.” art, with a re- Based on prior according combinant vector encoding examiner, “it A. would have been obvi- rejected examiner these claims 35 ous to under assemble other expression vectors 112(1) § U.S.C. for lack of containing enablement be- full length a-GalA se- cause the applicant had not deposited quences.” *8 targeting Gene is described in a quences-provides 1987 Cell a systematically means for (Kirk article Thomas and Mario Capecchi, altering genome.... the mammalian A de- by Site-Directed.Mutageneis Targeting Gene in sired alteration would first introduced be into Cells, Embryo-Derived Mouse Stem 51Cell sequence, a DNA gene cloned targeting (1987)) 503-12 (Oliver Smithies, 1985 Nature article would then transfer the into alteration the al., et Insertion DNA Se- of genome.” The Smithies article states: "[t]he quences Into the |3-glo- Human Chromosomal experiments reported here establish that the by Recombination, Homologous bin Locus planned specific modification of human (1985)), 317 Nature 230-34 both of gene accomplished be can in mammalian are of record. The Thomas article notes: by homologous cells recombination without targeting-the homologous "Gene recombina- detectably affecting parts ge- other of the sequences tion of DNA residing in the chro- nome.” newly mosome with introduced se- DNA not natu is protein recombinant pressed distinguish- by responded applicant particular aby normally expressed rally or appli- particular, art. prior
ing the pro “heterologoous A type. cell references tissue art prior noted cant skill by those of recognized transient, tein” is level, expres- only low achieved “whose protein recombinant being art as full-length when A human a-Gal of sion by is encoded acid amino introduced were cDNA 725; Glick, supra at gene.” cloned applicant, to the According cells. COS Dow, The T. J.A. Lackie and also J.M. see Tsuji and of systems expression transient Biology, Dictionary Cell Molecular a- produce utilized Bishop “could not of mean heterologous to (1999) (defining not could protein A, recombinant since Gal aof or DNA the tissues from “[d]erived ap- system.” The from be recovered Mi Encyclopedia species”); different contrast to “In of further stated: plicant ed., (Joshua Lederberg, crobiology, 1012 Applicants’ failures, to the art prior mean 2000) “heterologous” to (defining product, gene a-GalA human surprise, spe source a different from cell “derived in mammalian expressed stably when host”). Dr. Mell- cies; to the native not at remark- expressed only not is systems, ex the claimed suggest that did not selectively man actually levels, is but high ably of expression embraced method pression the host of levels out very high at secreted genes. of active recovery facile cell so finally possible.” made product is amendment, Moreover, clarifying in its of recovery then stressed applicant prior again that the stressed applicant of an A was element active expression the “stable art did teach method claims.2 pending A and isolation a-galaetosidase a-galactosidase active enzymatically persuade did arguments These sys- engineered mammalian an re- same issued the examiner, again who sys- expression Eukaryotic host tem.” “The selec- noted: The examiner jections. in tems, systems delineated such as promot- plasmids, appropriate tion of long have patent, the '804 5.2.1 of for lines section and cell ers, markers selectable the art of skill by those understood gene been is of the inserted expression proper facilitate selection, systems vector expression judicious merely a matter genes. See eukaryotic expression one ordi- ability of within the al., Biolo- Watson, Molecular et D. James further art.” Without narily skilled (“The (1987) more Gene, 614, 615 gy an recourse, submitted applicant expression how we learn about rejection under final after amendment more intelli- eucaryotes, clarify controlled amendment § 1.116. This C.F.R. vector expression develop we can gently the exam- disagreement points already en- Several factors systems.... IraDr. a declaration iner also included eucaryotie sys- development courage the declaration, Dr. Mellman In his Mellman. eucaryotie ex- tems the inventive surprise his asserted al., Labo- From Bright, et genes.”); Susan in the denied disclosed scheme pression Development ratory to Clinic: difficulty purifying claims, noting the *9 Immunology Reagent, Immunological pro- expressed recombinant heterologously (1991) (discussing “eukaryot- Today 130-31 ex- definition, heterologously a By teins. method of all enzyme is an element a-galacto- active active enzymatically 2. Secretion patent. the of the '804 claims of all claims A is an element sidase this patent, isolation of issued in the '804 H03 expression systems,” ic including CHO More important, the examiner cells transfected with an plas- could not accept second (supplemental) production mid for the of recombinant an- after-final amendment broadening the tibodies); (describ- Glick, supra, at 181-87 scope of rejected the claims without formal cell expression systems” “mammalian comment from applicant. the Under the being lines, composed of cell such as applicable Patent rules, Office amend cells, COS CHO engineered with patent ments to claims after rejection final mammalian expression vectors to express cannot alter the substantive scope of the heterologous proteins). words, In other claims explanation without about the ne applicant the expressly confined the inven- cessity of the amendment and without rea production tion to proteins by introduc- sons the delay in proposing the ing vectors into a mammalian host cell. change.3 1.116(b) (1992) § See 37 C.F.R. (“If persisted examiner in the re amendments touching the merits of jection until applicant submitted a sup application ... presented are after plemental amendment under 87 C.F.R. rejection final ... they may be admitted § 1.116. The replaced amendment upon showing good and sufficient rea phrase “transformed with a recombinant why they sons are necessary and were not vector which includes a nucleotide se presented.”). earlier If this amendment quence encoding a-galactosidase A” with markedly claims, broadened the it satisfied phrase “ehromosomally integrated nu neither of requirements. those The record sequence cleotide encoding a-galac supplies no explanation from applicant A.” tosidase The examiner applicant or the examiner that changes these were agreed on language during an after- “necessary” both and justifiably “not earli rejection final examiner interview. The presented.” Thus, er according to PTO record does not explain the reasons the rules, the examiner could not have allowed examiner finally accepted this language. this amendment if changed it at all the Contrary Genzyme’s position, scope of the claims set forth in deposit eleventh-hour amendment did not operate requirement, specification, the argu to broaden the claims to eliminate the ments of the applicant, and Dr. Mellman’s requirement of insertion of exogenous an declaration. gene into a host cell. place, the first The record suggests instead deposit requirement, specification, examiner felt this last-minute change did applicant’s arguments distinguish not alter the scope of the claims.
prior art, responses, examiner’s examiner’s comments did not distinguish Dr. Mellman’s declaration repeatedly newly these stressed that the amended claims the pri invention envisioned in- art, sertion of an but noted that simply a host cell. A clarifying had to recite that the a-Gal A amendment overex- was last moment negate could not pressed exten- Likewise, secreted. the appli public sive record. any cant did not change address 3. The Co., Inc., dissent contends that non-compliance Corp. Kelley awith Patent procedural (Fed.Cir.1987) Office rule is of no ("Kelley provided has neither consequence Dissent, once issues. evidence nor pre- inference to overcome However, slip. op. at presumes sumption this court complied PTO with its own complies rules.”). Therefore, Office Patent with its own support, without record rules, presumption only upon argument alleging overcome duty by dereliction of presentation contrary Rite-Hite evidence. examiner is without merit. *10 (Fed. Roussel, Inc., F.3d 1313 event, the Marion any In the claims.
scope reading Cir.2003), a broad any accorded which permitted have not could examiner Amgen the did expanded court in that This claims. 116 amendment to similar Rule exoge- introduction history the and prosecution make claims confront optional. into a host DNA the conclusively nous limits that specification In this claim terms. disputed of the indicates history Thus, prosecution the prose case, specification and integrated” “ehromosomally both the term that patentee exogenous a-Gal history indicate introduction requires cution cell. “chromosomally into the host inte sequences A term employed exogenous- these recited of the awith in a manner inconsistent grated” af- until sequences A a-Gal ly introduced envelopes meaning that broad textbook closed. was the merits on prosecution ter exogenous sources and endogenous both not show that simply does The record cell. in a host encoding genes sequences rules, vastly examiner, to PTO contrary al., Alberts, Biolo Molecular et Bruce See entering upon these claims broadened (1983) (discussing Cell, 247-50 gy to em- amendment after final supplemental into elements transposable integration of A a-Gal overexpression of brace Lewin, cells); supra at genomes of to a host cell. endogenous sequences (discussing the introduction 697-702 this only understand could public informed DNA into exogenous donor integration specifi- well as history, as prosecution stably ex generating cells in recipient itself, to language cation and transgenic ani cell lines pressing throughout as reflected Genzyme limit mals). Therefore, court did not district prosecution. term re construing this claim err if court reads TKT argues a host cell the introduction quire they Genzyme, suggested claims as encoding a-Gal A. sequences
H05 term, trict court erred in construing this “Stably” but the error is given harmless the proper The district court construed construction of the claim term “chromo- in “stably” “stably claim term the phrase somally integrated.” require overexpressed” to that “the nu sequence encoding a-galac- cleotide human III. stays place A in integrated tosidase once chromosome, i.e. into the the chromosomal After construing the claims of the change During is not transient.” prosecu patent, '804 granted district court tion, rejected the examiner the claims for summary judgment of noninfringement to 112(2). § under In re indefiniteness Summary judgment TKT. is appropriate gave sponse, applicant the examiner “if pleadings, depositions, answers to “stably,” namely definition “stable lev interrogatories, file, and admissions on to expression el and duration of the human affidavits, gether with any, if that show definition, ¥-galaetosidase gene.” A This genuine there is no any issue toas materi noted, applicant persistent as the “denotes al and that party fact the moving is enti expression, distinguished as from the tled to a judgment as a matter of law.” expression systems of short-term transient 56(c); Fed.R.Civ.P. Corp. Celotex Ca prior art.” trett, 317, 322, 2548, 477 U.S. S.Ct. 106 91 (1986). L.Ed.2d 265 In deciding whether a specification Indeed the discloses several genuine exists, issue of material fact working examples show stable justifiable court expression of human A draws all a-galactosidase inferences in the nonmovant’s gene. Liberty favor. Anderson v. specification particularly points 255, Lobby, out that the U.S. applicant high disclosed levels 106 S.Ct. L.Ed,2d (1986). expression can be achieved with not integrate vectors do into the above, noted As the TKT method Instead, host’s chromosome. these vectors overexpression gene involves activation. expres- achieve stable extra-chromosomal method, Under this TKT promot- inserts in transcription sion via pres- cDNA the ers into human host cells that on” “switch ence of a selectable marker. See '804 en- gene, cellular Thus, col. 63-67. coding protocol a-Gal A. TKT’s does not specification in invention as described exogenous genes introduce into host cells. expression by stable achieves chromosomal Genzyme hinged its claim of infringement integration and gene extra-chromosomal on a interpretation enough broad expression. applicant surrendered encompass TKT gene targeting. provided the extra-chromosomal embodiment of sta- declaratory showing evidence expression during prosecution. ble patent did not teach one art of skill
Thus, correctly the district court dis- method of ex- introducing workable an only ogenous gene sequence cerned that the claims embrace stable re- gene sequences integrated endogenous gene residing combine However, into a host’s chromosome. (gene targeting) chromosome specification history gene do facilitate activation. district stability validity issue, discuss terms dura- court did not decide this but instead, Rather, claims, change. tion of chromosomal construing after credit- applicant explicitly declaratory the term ed TKT’s its described evidence “stably” referring gene infringe the level and dura- activation method does Therefore, expression. tion Genzyme’s process. Genzyme the dis- it concedes *12 customary ordinary and of its scope full if the by TKT infringement show cannot meaning. the introduction require claims '804 sequences exogenous of cell
into a host CONSTRUCTION CLAIM I. re- the claims A. Because encoding a-Gal Meaning Customary element, Ordinary and A. exogenous quire finding precludes concession Genzyme’s jurisprudence in our settled is well It of the asserted infringes TKT their given are to be claim terms Therefore, district the patent. of meaning the to one customary and ordinary summary judgment granted properly court World art. Johnson in the relevant skill noninfringement TKT. 175 F.3d Assocs., Corp., of Inc. v. Zebco wide (Fed.Cir.1999). Determining the
985, 989 meaning of the customary CONCLUSION ordinary and step the first is of the claims terms construed properly court The district of the construction, and consultation claim “chromosomally integrat- term the claim history description written disputed construing the ed,” but erred the ordi ascertain attempting to before “stably.” sequence” “regulatory terms the lan meaning of customary nary of the the construction However, because Tex. premature. of the claims guage “chromosomally integrated” claim term Inc., 308 Telegenix, v. Sys., Inc. Digital infringe- showing from Genzyme precludes (Fed.Cir.2002). Where 1193, 1204 F.3d are harmless. ment, latter errors these “de- a claim term of choice patentee’s the district Therefore, affirms this court ” clarity,’ CCS Fit the claim privets] summary judgment. grant court’s ness, Corp., Inc. Brunswick however, (Fed.Cir.2002), 1359, 1367 COSTS intrinsic to the other must court “resort its own costs. shall bear party Each meaning of evidence,” id., to determine the claim terms. AFFIRMED. view, majority hastens too my In concurring-in-part LINN, Judge, Circuit of deter- step past the fundamental quickly dissenting-in-part. customary mean- ordinary and mining the con- majority’s It re- “chromosomally integrated.” I concur
While “regulato- “integration,” the claim limitations single on a definition struction lies I another “stably overexpressed,” in the of “viral context ry sequence” defined concept of from its conclu- import dissent sequence,” to respectfully must DNA 1098; at slip op. Genzyme, genome.” construction regarding sion “host (1990). In Lewin, integrated” Benjamin limitation. Genes IV “chromosomally a “host concept of this imported view, my light the restriction ambiguity as majority perceives into a cell,” introduction require the limitation art at the encoding one of skill sequences to “whether “exogenous host 1105, unad- would understand of the invention A,” op. time slip Genzyme, ¥-Gal outside to come from the specifi- limitations visedly reads vector, cell, or from within i.e., a no discern the host I can claims. cation chro- cell but outside critical the host give would do so and proper basis i.e., element.”4 mosome, transposable limitation “chromosomally integrated” "chromosom- as whether question analysis frames construction majority’s 4. The Genzyme, slip op. at 1098. It then turns to copies [viral] DNA become integrated into the specification to perceived resolve this genome.”), and the transposition ambiguity. yeast transposable elements from one site to another within all genome,
With due same respect my colleagues, id. at 681 (describing yeast there is no ambiguity Ty transposa- here to be resolved. *13 ble elements majority subject as opinion establishes that “reverse tran- scription term “chromosomally integration”). integrated” could Transposable elements, used in reference to the such incorporation as retroposons, into were un- a chromosome of derstood at either endogenous or time ex- to be a part of an ogenous DNA, organism’s is to say, own genome. (“[W]e DNA se- Id. at 672 quences that have their origin think of either retroposons inside genomic as (duplex or outside DNA) the cell to which chromo- that occasionally trans- some is native. The ordinary and custom- within pose genome; they do not migrate ary meaning of the broadly term cells.”). encom- between Another contemporane- passes both possibilities. It is incorrect to leading ous text similarly describes both perceive a claim term ambiguous as mere- viral DNA and transposable element DNA ly because of its breadth and to require as integrating into the chromosome. that the term be redefined to encompass al., Bruce Alberts et Molecular Biology of only a portion of its ordinary meaning in (1989) (“[T]he the Cell 255 DNA circle [of clarity. name of transposable integrates element] into a randomly
Technical treatises selected publicly site on available at the chromo- some.”) the time a patent is may issued The term be consult “chromosomally inte- as ed grated” “reliable sources of was thus commonly information that by understood would have been attributed to those in terms of skill the art at the time to refer the claims by those of skill in the art.” incorporation chromosome Digital Tex. Sys., 308 F.3d at DNA 1202-03. that either came from another site in also See Inverness Med. Switz. v. GmbH genome the same or from outside the cell. Princeton Corp., Biomeditech 309 F.3d This is the ordinary and customary mean- 1365, (Fed.Cir.2002) (‘We 1370 look, may ing of the claim term.
therefore, to the dictionary definition of the claim term mobility of the date the B.The Intrinsic Record issued.”). patents A review of the relevant technical The next step in treatises the claim contemporaneous construction with case, process issuance the '804 as in case, every shows that is to “chromosomally integrated” examine the evidence, intrinsic had a broad comprising meaning, claims, encompassing integration the written description, and the both and endogenous prosecution history if evidence, DNA. The to deter Genes IV text that the majority mine cites whether patentee uses has rebutted term “integrated” to describe both the the presumption that “chromosomally inte incorporation of viral DNA of extracellular grated” has its ordinary and customary origin, (1990) (“One Genes IV 674 or more meaning. See Brookhill-Wilk LLC v. ally integrated” can be construed to "cover a allegedly infringing technique. I believe the gene activation technique only question which is precedent misdirected. Our in- promoter sequence is inserted into a human forms that "claims [should] not be construed
host cell in order to activate the geneA by ct-Gal reference to the accused device.” Neo- already present cell,” in the host Genzyme, Magic Corp. Inc., Microsys., v. Trident 287 slip op. at which description is a of TKT’s (Fed.Cir.2002). F.3d 1074
1108 embodi- to the limited regularly be 1294, would F.3d 334 Surgical, Intuitive But it specification. disclosed Digital Sys., ments Tex. (Fed.Cir.2003); embodi- may language, rebut the claim patentee 1204. A F.3d claim terminol PLC “defin[ing] Renishaw ments, See by control. presumption its ordi Azioni, with F.3d inconsistent per manner ogy in a Marposs Societa’ v. Corp. Int’l ([T]he meaning,” Biovail nary (Fed.Cir.1998) 1243, 1248 1297, 1301 Pharms., Inc., F.3d exclude; Andrx right to of the define particu disclaiming (Fed.Cir.2001), or therefore, inquiry, claim construction during term aof interpretation lar the actual in all cases and ends begins v. Loredan Corp. Biodex prosecution, claim.). words (Fed. 850, 863 Biomedical, Inc., 946 F.2d *14 of “Summary the majority also cites the of Cir.1991). no redefinition I find evidence, section, present do where “the nor Invention” in the term the claim intrinsic the cell ex coverage “host to involve any disclaimer is said invention” I discern abstract, DNA. endogenous the integration and systems,” pression '804 host cells.” “engineered refers to “integration” or “integrated” The word 22-25; 6, Abstract. 11 col. sixty-page patent, in the nine times appears cell” “host in that the term majority contends None these description. written “special of ex introduction amounts the necessarily implies its on own stances in the clearly material, amounts ... stated and this definition genetic ogenous Concep Corp. v. Vitronics specification.” Gen- invention.” a “definition the (Fed.Cir. 1576, Inc., 1582 tronic, 90 F.3d (cid:127) In other 1099-1100. at slip op. zyme, that correctly notes 1996). majority a redefinition words, sees majority the term uses the consistently applicant “the “chromosomally integrat claim term the in foreign gene ato to refer ‘integrated’ of a specification in in the use the ed” Gen cell chromosome.” into a host serted in cell,” term, appears nowhere that “host However, this use of op. at zyme, slip view, majority my the In claims. the [its] not “inconsistent “integrated” of a redefini in far afield search roams too ' 90 Corp., meaning,” Vitronics ordinary our clear from It is claim term. tion used 1582, cannot therefore F.3d focus must any redefinition that precedent has redefined patentee to show employed actually term on the clarity, deliber reasonable “with the term N. Ficosa v. Teleflex, Inc. See claims. Paulsen, 30 re ateness, precision,” (Fed.Cir. 1313, 1324 F.3d Corp., 299 Am. (Fed.Cir.1994). theAs 1475, 1480 F.3d (“The 2002) defines language claim demonstrates, ordinary majority Interactive scope.”); of claim bounds Gift em “integrated” meaning of customary Inc., F.3d 256 Compuserve Express, Inc. both incorporation braces (“In construing (Fed.Cir.2001) 1823, 1331 immaterial It is DNA. begin must claims, analytical focus “integrated” construction proper language on the centered remain consistently employ embodiments language themselves, it is that redefinition Absent a exogenous DNA. ‘particu use to patentee chose term, consis relating to a claim disclaimer distinctly claim[ ] out and larly point[ ] of a description in written tent use regards patentee which the subject matter trump meaning cannot term a narrower ”); Inc. v. Thermalloy, his invention.’ customary mean ordinary and a broader (Fed. 691, Inc., 121 F.3d 693 Eng’g, Aavid claim. Were as used in ing the term Cir.1997) interpretation (“[throughout terms claim otherwise, scope of it
1109
process, the focus
on the meaning
remains
prosecution and does not appear in the
of claim language.”).
issued claims. See
Snow,
Smith v.
294
1, 16,
U.S.
279,
55 S.Ct.
Despite the removal limitation, of that that if it were in fact broadening, however, the majority maintains that the amendment would been have a violation of deposited vector sequence remained 1.116(b), neces- 37 C.F.R. because the patentee sary to invention, the claimed and this made showing no good of and sufficient a mandates restriction of the scope of why reasons necessary [it was] [was] “chromosomally integrated.” I cannot not presented. 1.116(b) earlier 37 C.F.R. agree. The deposit (1992). of the recombinant A decision restricting scope of vector required was by the to Examiner an otherwise unambiguous claim term establish enablement then-pending of based an applicants on presumed noncom- claims explicitly that required its pliance use. with a procedural rule of the PTO When the use of a recombinant vector was strikes me as ill-founded. See Dethmers claims, eliminated from the predicate Co., Mfg. Inc. v. Automatic Equip. Mfg. for the Examiner’s deposition requirement Co., (Fed.Cir.2002) evaporated. There is (Linn, J., no reason to con- dissenting deny- the order clude in this case that an banc) ([0]nee action taken as rehearing en a patent result of the presence specific issues, of a term in non-compliance with procedural the claims should continue to bind the rule administered by the PTO within the patentee when term is removed scope dur- of the agency’s statutory authority integrated art references prior of the the grant found, virtue by chromo- a different DNA into own during pros- cell’s satisfied been to have
patent, at issue. itself, simply no conse- was somal site is, and of ecution quence.). arguments on relies majority also ENABLEMENT II. references art prior certain distinguishing record that “the majority notes “expressly patentee
to establish enable- questions of to raise appear would production invention confined “this ment,” it states although also into a introducing vectors proteins enablement not examine need court op. slip Genzyme, cell.” mammalian ‘chromo- claim term define properly or a disclaimer To establish at 1102-1103. specifica- in view somally integrated’ course, pat- scope, of claim disavowal history.” Genzyme, tion expressions must use “words entee that en- the extent To op. slip restriction, repre- exclusion manifest majority’s concerns underlie ablement scope.” a clear disavowal senting “chromosomally narrowing 1204. The F.3d at Digital Sys., Tex. however, suggest that such I integrated,” manifest exclusion finds such majority consideration. yet ripe are not issues DNA in a cell’s own the use of yet addressed court has district that the claimed assertions patentee’s brief the did not parties and the recovering validity, “re- capable was invention court has Although this appeal. “hetero- on and that such issue protein,” combinant interpreted so proteins” should recombinant stated expressed logously rea- slip op. validity whenever Genzyme, their purify. preserve are difficult *16 Mfg. referred Co. Unit- patentee also sonably possible, Modine at 1101-1102. Comm’n, engi- “an use invention’s Int’l the claimed ed Trade States Id., slip system.” (Fed.Cir.1996), wrong to it is cell mammalian neered disavowal yet no clear I see that have 1102-1103. issues op. at allow enablement in these endogenous DNA and the parties of the use of ventilated fully been em- Bishop Tsuji nor a claim construc- Neither remarks. influence district court essence of DNA. all validi- agree that ployed I tion determination. that, while was day. patentee’s argument left for another should ty concerns DNA to employed art prior expression, of transient a low level achieve first dem- “the was invention
the claimed stable, overexpression,
onstration secretion, subsequent iso-
selective a recombi- enzyme in lysosomal of a
lation system.” Whether
nant mammalian notes this court Indeed be invalid. would do figures Sequence” specification “Regulatory that the '804 activating en any methods not discuss “regu court construed The district sequences. A a-Gal dogenous occurrence to in the first sequence” latory does not discuss fact, specification required sequences all “any and mean sequences integrated” “ehromosomally a-galactosi the human gene expression the host genes A within one of at least consisting gene, A dase Thus, appear the record would all. cells at gene expres promotes See of enablement. questions to raise 9-14, of the '804 sion.” Column Int’l States Mfg. Co. Modine United regu examples several discloses (Fed. Comm’n, Trade ex are appropriate latory Cir.1996) “so (this interprets claims court elements. While pression control validity” whenever their preserve as to requiring process court, teaches specification The district possible”). “reasonably issues, these elements trans however, validity more of not decide did one DNA, it does enablement not examine with a-Gal this court need form cells term “chromo- required. the claim properly define them are that all of teach specifi view somally integrated” regard, in this but court erred district history. cation in view of trial is harmless error of the claim proper construction court’s case also notes This court “ehromosomally integrated.” term v. Hoechst Amgen Inc. different