13051317 (P.T.A.B. Aug. 16, 2016)

Ex Parte Hansen et al

Patent Trial and Appeal BoardAug 16, 2016

13051317 (P.T.A.B. Aug. 16, 2016)

UNITED STA TES p A TENT AND TRADEMARK OFFICE APPLICATION NO. FILING DATE 13/051,317 03/18/2011 27495 7590 08/18/2016 Agilent Technologies, Inc, in care of: CPA Global P. 0. Box 52050 Minneapolis, MN 55402 FIRST NAMED INVENTOR Connie Hansen UNITED STATES DEPARTMENT OF COMMERCE United States Patent and Trademark Office Address: COMMISSIONER FOR PATENTS P.O. Box 1450 Alexandria, Virginia 22313-1450 www .uspto.gov ATTORNEY DOCKET NO. CONFIRMATION NO. 10070431-11-US 4289 EXAMINER RAMIREZ, DELIA M ART UNIT PAPER NUMBER 1652 NOTIFICATION DATE DELIVERY MODE 08/18/2016 ELECTRONIC Please find below and/or attached an Office communication concerning this application or proceeding. The time period for reply, if any, is set in the attached communication. Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the following e-mail address( es): IPOPS.LEGAL@agilent.com Agilentdocketing@cpaglobal.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte CONNIE HANSEN, HOLLY HOGREFE, MICHAEL BORNS, and MICHAEL MUHICH Appeal2014-000733 Application 13/051,317 Technology Center 1600 Before DONALD E. ADAMS, JEFFREY N. FREDMAN, and TIMOTHY G. MAJORS, Administrative Patent Judges. ADAMS, Administrative Patent Judge. DECISION ON APPEAL 1 This appeal under 35 U.S.C. Â§ 134(a) involves claims 96-98 and 101- 114 (Br. 6). Examiner entered rejections under the enablement and written description provisions of 35 U.S.C. Â§ 112, first paragraph, 35 U.S.C. Â§ 112, second paragraph, and obviousness-type double patenting. We have jurisdiction under 35 U.S.C. Â§ 6(b ). We AFFIRM. 1 Appellants identify the Real Party in Interest as "Agilent Technologies, Inc." (Br. 4 ). Appeal2014-000733 Application 13/051,317 STATEMENT OF THE CASE Appellants' disclosed "invention relates to the fields of nucleic acid polymerases and nucleic acid polymerization reactions" (Spec.2 1 ). Independent claim 96 is representative and reproduced below: 96. A composition of matter comprising: at least one DNA polymerase; and an in vitro produced thermostable nucleic acid polymerase enhancing factor (PEP) having dUTPase activity, wherein the PEP includes a uridine binding domain that is encoded by a nucleotide sequence that hybridizes to a nucleic acid comprising a sequence encoding anyone of SEQ ID NOs:73-81 under hybridization conditions of 5xSSC and 50% formamide at 42Â°C, and under washing conditions of O.lxSSC and 0.1 % sodium dodecyl sulfate at 60Â°C. Claim 101, the only remaining independent claim before this panel for review, is drawn to a kit for replicating nucleic acids in vitro, wherein the kit comprises the composition of claim 96. GROUNDS OF REJECTION Claims 96, 101, 104--108, and 110-114 stand rejected under 35 U.S.C. Â§ 112, second paragraph. Claims 96, 101, 105-108, and 111-114 stand rejected under the written description provision of 35 U.S.C. Â§ 112, first paragraph. Claims 96, 97, 101, 105-108, and 111-114 stand rejected under the written description provision of 35 U.S.C. Â§ 112, first paragraph. Claims 96, 97, 101, 105-108, and 111-114 stand rejected under the enablement provision of 35 U.S.C. Â§ 112, first paragraph. 2 All reference to Appellants' Specification refers to Appellants' June 6, 2011 Specification. 2 Appeal2014-000733 Application 13/051,317 Claims 96-98 and 101-114 stand rejected under the judicially created doctrine of obviousness-type double patenting as being unpatentable over one or more claims of Hogrefe '997,3 Hogrefe '2164, Hogrefe '070,5 Hansen,6 Borns'100,7 Borns '645,8 and Borns' 157.9 Obviousness-type Double Patenting: Appellants do not contest the obviousness-type double patenting rejections (see Ans. 28). Therefore, these rejections are summarily affirmed. See MANUAL OF PATENT EXAMINING PROCEDUREÂ§ 1205.02 ("If a ground of rejection stated by the examiner is not addressed in the appellant's brief, that ground of rejection will be summarily sustained by the Board."). Definiteness: ISSUE Does the preponderance of evidence support Examiner's conclusion that the phrases "nucleotide sequence that hybridizes to a nucleic acid" and "nucleotide sequence that hybridizes to the complete complement of a nucleic acid," as set forth in Appellants' claims 96, 101, 104, and 110, are indefinite? 3 Hogrefe, US 6,183,997 Bl, issued Feb. 6, 2001. 4 Hogrefe et al., US 6,803,216 B2, issued Oct. 12, 2004. 5 Hogrefe et al., US 7,932,070 B2, issued Apr. 26, 2011. 6 Hansen et al., US 7,943,358 B2, issued May 17, 2011. 7 Borns et al., US 7,659,100 B2, issued Feb. 9, 2010. 8 Borns, US 7,939,645 B2, issued May 10, 2011. 9 Borns, US 7,960,157 B2, issued June 14, 2011. 3 Appeal2014-000733 Application 13/051,317 ANALYSIS Examiner finds that "a nucleotide sequence is a graphical representation of the order in which nucleotides are arranged in a nucleic acid molecule" and "hybridization occurs among nucleic acid molecules" (Ans. 2). "Therefore," Examiner finds "it [] unclear as to how a sequence can hybridize to a molecule" (id.). We are not persuaded. Instead, we find that Appellants' claims are clear and unambiguous, to those of ordinary skill in this art, when read in context and as a whole. Therefore, we agree with Appellants' contention: "Because the skilled artisan would understand the metes and bounds of independent claims 96 and 101, those claims, and their dependent claims, do not lack clarity" (Br. 17). CONCLUSION OF LAW The preponderance of evidence fails to support Examiner's conclusion that the phrases "nucleotide sequence that hybridizes to a nucleic acid" and "nucleotide sequence that hybridizes to the complete complement of a nucleic acid," as set forth in Appellants' claims 96, 101, 104, and 110, are indefinite. The rejection of claims 96, 101, 104--108, and 110-114 under 35 U.S.C. Â§ 112, second paragraph is reversed. Written Description: ISSUE Does the preponderance of evidence on this record support Examiner's finding that Appellants' Specification fails to provide written descriptive support for the claimed invention? 4 Appeal2014-000733 Application 13/051,317 FACTUAL FINDINGS (FF) FF 1. Examiner finds that Appellants' Specification "discloses the structure of a single species of the [] genus [recited in Appellants' claim 96] of thermostable proteins which ha[ ve] [both] polymerase enhancing and dUTPase activity (i.e., the polypeptide of SEQ ID NO: 71 which is disclosed as a dUTPase)" (Ans. 5). FF 2. Examiner finds that while Appellants' claim 96 "require[s] uridine binding domains which are [] structural homologues of the uridine binding domains of SEQ ID NO: 73-81, it is noted that the presence of such uridine binding domains [are] not necessarily associated with thermostable dUTPase activity as other enzymes also comprise uridine binding domains" (id.). FF 3. Examiner finds that "the uridine binding domains of SEQ ID NO: 74-77[, which fall within the genus ofuridine binding domains recited in Appellants' claim 96,] do not belong to dUTPases but rather to dCTP deaminases" (id.). FF 4. Examiner finds that "the uridine binding domains of SEQ ID NO: 78-81 [,which fall within the genus of uridine binding domains recited in Appellants' claim 96,] belong to dUTPases from non-thermophilic organisms" (id.). FF 5. Examiner finds that neither [Appellants'] [S]pecification nor the prior art at the time of the invention provide [] information as to the structural elements required in any thermostable protein[, within the scope of Appellants' claim 96, that] hav[ e] [both] the desired polymerase enhancing and dUTPase activity, nor do they teach 5 Appeal2014-000733 Application 13/051,317 which fragments of SEQ ID N 0: 71 need to be present for that protein to have the desired thermostable activity. (id.; see also id. at 6 ("neither [Appellants'] [S]pecification nor the prior art at the time of filing provides any information as to how to recognize which variants having the[] amino acid modifications [encompassed by Appellants' claim 96] have the desired thermostable activity" or what "structural features [are] required in any dUTPase for that dUTPase to be thermostable")). FF 6. Examiner finds that neither Appellants' "[Specification] [n]or the [prior] art [provide] an art-recognized correlation between structure and thermostable dUTPase activity or thermostable polymerase enhancing activity" (Ans. 6; see id. at 7). FF 7. Examiner relies on Witkowski10 and Seffemick11 to establish that "small changes in [protein] structure can lead to changes in activity" (Ans. 7). ANALYSIS We vacate, and will not further discuss, the first rejection of claims 96, 101, 105-108, and 111-114 under the written description provision of 3 5 U.S.C. Â§ 112, first paragraph, new matter (Ans. 2--4), as cumulative to the second rejection of claims 96, 97, 101, 105-108, and 111-114 under the written description provision of 35 U.S.C. Â§ 112, first paragraph (Ans. 4--8). 10 Witkowski et al., Conversion of a fJ-Ketoacyl Synthase to a Malonyl Decarboxylase by Replacement of the Active-Site Cysteine with Glutamine, 38 Biochemistry 11643-11650 (1999). Cited on Appellants' June 21, 2011 Information Disclosure Statement. 11 Seffemick et al., Melamine Deaminase and Atrazine Chlorohydrolase: 98 Percent Identical but Functionally Different, 183 J. Bacteriol. 2405-2410 (2001 ). Cited on Appellants' June 21, 2011 Information Disclosure Statement. 6 Appeal2014-000733 Application 13/051,317 Examiner finds that because Appellants' [S]pecification only discloses a single species of the genus, i.e., the polypeptide of SEQ ID NO: 71, and the lack of description of any additional species by any relevant, identifying characteristics or properties, one of skill in the art would not recognize from [Appellants'] disclosure that [Appellants] w[ ere] in possession of the [subject matter encompassed by Appellants'] claimed invention. (Ans. 8.) In this regard, Examiner finds that because "minor structural changes to a polypeptide may result in changes affecting function, and no additional information correlating structure with the desired thermostable dUTPase activity has been provided, one cannot reasonably conclude that SEQ ID NO: 71 is representative of the structure of all the proteins [encompassed] by [Appellants'] claim[] [96]" (Ans. 7). Appellants' claim 96 requires, inter alia, "an in vitro produced thermostable nucleic acid polymerase enhancing factor (PEP) having dUTPase activity" (see Appellants' claim 1 ). Therefore, we are not persuaded by Appellants' contention that "the structure of a given dUTPase as it relates to dUTPase activity is not a relevant consideration for the present claims" (App. Br. 18; see id. at 21-22). We recognize, but are not persuaded by, Appellants' contention that "Appellants [] clearly considered PEP proteins comprising the recited sequences as part of their invention at the time of filing," because Appellants' so state in their "original claim 85" and at various portions of their Specification (App. Br. 18). "[A] patentee of a biotechnological invention cannot necessarily claim a genus after only describing a limited number of species because there may be unpredictability in the results obtained from species other than those specifically enumerated." In re 7 Appeal2014-000733 Application 13/051,317 Alonso, 545 F.3d 1015, 1020 (Fed. Cir. 2008) (citing Noelle v. Lederman, 355 F.3d 1343, 1350 (Fed. Cir. 2004). The question, therefore, is not, as Appellants' contend, whether "the activity of different DNA polymerases, can be improved by the inclusion of a PEP in the reaction mixture" (App. Br. 19). To the contrary, the question is whether Appellants' provided written descriptive support for the genus of thermostable nucleic acid polymerase enhancing factor (PEP) having dUTPase activity, wherein the PEP includes a uridine binding domain that is encoded by a nucleotide sequence that hybridizes to a nucleic acid comprising a sequence encoding anyone of SEQ ID NOs: 73-81 under hybridization conditions of 5xSSC and 50% formamide at 42Â°C, and under washing conditions of O. lxSSC and 0.1 % sodium dodecyl sulfate at 60Â°C encompassed by Appellants' claim 96 (see Appellants' claim 96; cf FF 1- 7). We recognize, but are not persuaded by, Appellants' contention that Appellants' substitute specification, at page 20, first full paragraph, [] discloses that the crystal structure of at least one dUTPase was known at the time of filing of the application, and that those of skill in the art could use publicly available information to guide them in targeting residues (or avoiding residues) for mutation/ alteration. (App. Br. 19.) On this record, Appellants' claim 96 requires the PEP to have: (1) a modicum of structure, i.e., "a uridine binding domain that is encoded by a nucleotide sequence that hybridizes to a nucleic acid comprising a sequence encoding anyone of SEQ ID NOs: 73-81 under [the specified] hybridization conditions" and (2) dUTPase activity. As Examiner explains, the limited structural requirements set forth in Appellants' claim 96 8 Appeal2014-000733 Application 13/051,317 do not allow the ordinary artisan to identify the genus of PEF structures that can satisfy the recited activity even though the crystal structure of at least one dUTPase is known in the art (see FF 1-7). Appellants failed to provide persuasive evidence or argument to rebut Examiner's findings. In this regard, we note that, notwithstanding Appellants' contention to the contrary, the written description requirement "requires a description of an invention, not an indication of a result that one might achieve if one made that invention." Regents of the University of California v. Eli Lilly & Co., 119 F.3d 1559, 1568 (Fed. Cir. 1997). Stated differently, to comply with the written description requirement, Appellants must "describe [] the invention, with all its claimed limitations, not that which makes it obvious." Id. at 1566 (citation omitted). We recognize, but are not persuaded by, Appellants' contention that their Specification discloses the full sequences of three dUTPases (specifically, "thermophilic P. furiosus PEP," "thermophilic Archaea Methanococcus jannaschii and Desulfurolobus ambivalens") (App. Br. 19). As Examiner explains, Appellants' Specification describes the Methanococcus jannaschii and Desulfurolobus ambivalens proteins as "dCTP deaminases []not dUTPases" (Ans. 21 (emphasis removed), citing Appellants' Specification 46 and 52: Table; see also Ans. 21 (Examiner notes that "DCD[, as it is used in Appellants' Specification,] is an abbreviation for dCTP deaminase")). In addition, Examiner finds that, notwithstanding Appellants' contention to the contrary, the Methanococcus jannaschii and Desulfurolobus ambivalens sequences disclosed by Appellants are not full length sequences, but are instead "14 amino acids each corresponding to SEQ ID NO: 74--76" (Ans. 21). Thus, for the reasons 9 Appeal2014-000733 Application 13/051,317 provided by Examiner and discussed above, we find that the limited examples of dUTPases disclosed by Appellants do not adequately describe the entire genus of PEP variants encompassed by Appellants' claim 96 because the structure of other members of the genus cannot be predicted based on the disclosure since common characteristics among members of the genus have not been described (see FF 1-7). In this regard, we recognize that "Appellants agree that the[ir] specification does not assert that the disclosed uridine binding domain is a structural feature found only in proteins having dUTPase activity" and concede that "the skilled artisan would recognize that the disclosed uridine binding domain is shared among proteins that bind uridine, including those showing dUTPase activity" and those that do not (App. Br. 21 ). In sum, we find that Examiner established that Appellants' Specification fails to provide written descriptive support for the genus of PEFs encompassed by Appellants' claim 96. Therefore, for the same reasons, Appellants' Specification fails to provide written descriptive support for a kit that comprises the composition of claim 96 (see Appellants' claim 101 ). CONCLUSION OF LAW The preponderance of evidence on this record supports Examiner's finding that Appellants' Specification fails to provide written descriptive support for the claimed invention. The rejection of claims 96 and 101 under the written description provision of 35 U.S.C. Â§ 112, first paragraph is affirmed. Claims 97 and 111-114 are not separately argued and fall with claim 96. Claims 105-108 are not separately argued and fall with claim 101. 10 Appeal2014-000733 Application 13/051,317 Enablement: Does the evidence of record support Examiner's conclusion that undue experimentation would be required to practice the claimed invention? ANALYSIS Examiner finds that Appellants' Specification provides an enabling disclosure of "a composition comprising the polypeptide of SEQ ID NO: 71, and a kit comprising [that] composition" (Ans. 9). Examiner, however, finds that Appellants' Specification fails to enable the full scope of Appellants' claimed invention (see id. at 8-9; see generally id. 8-11 ). In this regard, Examiner finds that "it was not routine in the art to screen by a trial and error process for any number of polypeptides and determine whether such polypeptide is a thermostable PEP having dUTPase activity (Ans. 10). Examiner, however, fails to provide an evidentiary basis on this record to support this assertion. To the contrary, the evidence relied upon by Examiner suggests that minor changes in protein structure may alter protein activity (see Ans. 10). Examiner's evidence does not establish that it would have required undue experimentation to screen PEP proteins that fall within the scope of Appellants' claimed invention for dUTPase activity. See, e.g., Johns Hopkins Univ. v. Cellpro, Inc., 152 F.3d 1342, 1360 (Fed. Cir. 1998), citing PPG Indus., Inc. v. Guardian Indus. Corp., 75 F.3d 1558, 1564 (Fed. Cir. 1996) ("The test [for undue experimentation] is not merely quantitative, since a considerable amount of experimentation is permissible, if it is merely routine" (alteration original)). Thus, on this record, Examiner failed to establish an evidentiary basis to support a finding that screening PEP proteins that fall within the scope of Appellants' claimed invention for dUTPase activity was not routine in this art. Therefore, we are compelled to 11 Appeal2014-000733 Application 13/051,317 agree with Appellants' contention that identifying and screening proteins that fall within the scope of Appellants' claimed invention required no more than routine experimentation in this art (see App. Br. 26). CONCLUSION OF LAW The evidence of record fails to support Examiner's conclusion that undue experimentation would be required to practice the claimed invention. The rejection of claims 96, 97, 101, 105-108, and 111-114 under the enablement provision of 35 U.S.C. Â§ 112, first paragraph is reversed. TIME PERIOD FOR RESPONSE No time period for taking any subsequent action in connection with this appeal may be extended under 37 C.F.R. Â§ 1.136(a). AFFIRMED 12