Gregory Lohman et al.Download PDFPatent Trials and Appeals BoardOct 21, 201913829489 - (D) (P.T.A.B. Oct. 21, 2019) Copy Citation UNITED STATES PATENT AND TRADEMARK OFFICE 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 APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO. 13/829,489 03/14/2013 Gregory Lohman NEB-365-US 1953 28986 7590 10/21/2019 HARRIET M. STRIMPEL, D. Phil. New England Biolabs, Inc. 240 COUNTY ROAD IPSWICH, MA 01938-2723 EXAMINER BROWN, MINDY G ART UNIT PAPER NUMBER 1636 NOTIFICATION DATE DELIVERY MODE 10/21/2019 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): STRIMPEL@NEB.COM mcgrane@neb.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE ____________ BEFORE THE PATENT TRIAL AND APPEAL BOARD ____________ Ex parte GREGORY LOHMAN, THOMAS C. EVANS, and LARRY A. MCREYNOLDS ____________ Appeal 2018-006629 Application 13/829,4891 Technology Center 1600 ____________ Before JEFFREY N. FREDMAN, TAWEN CHANG, and DAVID COTTA, Administrative Patent Judges. COTTA, Administrative Patent Judge. DECISION ON APPEAL This is an appeal under 35 U.S.C. § 134(a) involving claims to a method of ligating DNA polynucleotide sequences. The Examiner rejected the claims on appeal as obvious under 35 U.S.C. § 103(a). We have jurisdiction under 35 U.S.C. § 6(b). We reverse. 1 We use the word “Appellant” to refer to “applicant” as defined in 37 C.F.R. § 1.42. According to Appellant, the real party in interest is New England Biolabs, Inc. App. Br. 3. Appeal 2018-006629 Application 13/829,489 2 STATEMENT OF THE CASE The Specification discloses that “[l]igation of single stranded (ss) DNA oligonucleotides splinted by complementary RNA is an essential step in techniques such as RNA mediated annealing, selection, and ligation (RASL).” Spec. 1. According to the Specification, T4 DNA ligase has been used for RASL, but “works poorly requiring, for example, long incubation times, high concentrations of ligase, and low ATP concentrations to overcome the preferential formation of adenylated DNA side products.” Id. Various other ligases have been tested but proved unsuccessful including, T4 RNA ligase, NAT+ dependent ligase from Melanoplus sanguinipes entomopoxvirus, PBCV-1 DNA ligase from Chlorella, NAD-dependent E. Coli DNA ligase, and human DNA ligase 1, “leading to a conclusion that these ligases could not accept RNA-splinted DNA as ligation substrates.” Id. at 2. The Specification discloses a ligase that “surprisingly ligates ssDNA oligonucleotides splinted by a ssRNA with high efficiency.” Id. at 9. The Specification reports: Contrary to the publication describing PBCV-1 ligase as inactive in ligating DNA oligonucleotides together on an RNA splint (Sriskanda, et al., (1998)), it has here been shown here that ssDNA oligonucleotides of a size greater than 8 nucleotides can surprisingly be ligated together to form a single oligonucleotide of at least 16 nucleotides when splinted by a complementary RNA with an efficiency that is greater than 10 fold to 1000 fold over T4 DNA ligase. Id. at 10. Claims 16, 20, 21, 23–31, 33, and 34 are on appeal. Claim 16 is illustrative and reads as follows: Appeal 2018-006629 Application 13/829,489 3 16. A method for ligating DNA polynucleotide sequences, comprising: (a) obtaining RNA from a sample that comprises cells or a bodily fluid to produce an RNA sample comprising naturally- occurring RNAs; (b) hybridizing at least two DNA polynucleotide sequences to a naturally occurring RNA in the RNA sample; (c) ligating the at least two DNA polynucleotide sequences to one another using a ligase that has an amino acid sequence that is at least 90% identical to the Chlorella virus PBCV-1 ligase of SEQ ID N0:1: and (d) detecting the product of step (b). App. Br. 15. The claims stand rejected as follows. Claims 16, 20, 21, 23–28, and 34 were rejected under 35 U.S.C. § 103(a) as obvious over the combination of Sriskanda,2 Ho,3 and Namsaraev.4 Claims 29–31 and 33 were rejected under 35 U.S.C. § 103(a) as obvious over the combination of Sriskanda, Ho, Namsaraev, Nilsson,5 and Nilsson 2.6 2 Sriskanda et al., Specificity and Fidelity of Strand Joining by Chlorella Virus DNA Ligase, 26(15) Nucleic Acids Research 3536–3541 (1998) (“Sriskanda”). 3 Ho et al., Characterization of an ATP-Dependent DNA Ligase Encoded by Chlorella Virus PBCV-1, 71(3) Journal of Virology 1931–1937 (1997) (“Ho”). 4 Namsaraev et al., US Patent Publication No. 2010/0184618 A1, published July 22, 2010 (“Namsaraev”). 5 Nilsson et al., RNA-Templated DNA Ligation for Transcript Analysis, 29(2) Nucleic Acids Research 578–581 (2001) (“Nilsson 1”). 6 Nilsson et al., Enhanced Detection and Distinction of RNA by Enzymatic Probe Ligation, 18 Nature Biotechnology 791–793 (2000) (“Nilsson 2”). Appeal 2018-006629 Application 13/829,489 4 Claims 16, 20, 21, 23–30, and 34 were rejected under 35 U.S.C. § 103(a) as obvious over the combination of Namsaraev and Ho. Claims 30 and 31 were rejected under 35 U.S.C. § 103(a) as obvious over the combination of Namsaraev, Ho, Nilsson, and Nilsson 2. OBVIOUSNESS OVER SRISKANDA, HO, AND NAMSARAEV In finding claims 16, 20, 21, 23–28, and 34 obvious, the Examiner found that Sriskanda disclosed all of the “active method steps” recited in independent claim 16 and, in addition, taught “the same reaction conditions as provided by applicant in the examples of the . . . [S]pecification.” Ans. 4. The Examiner acknowledged, however, that Sriskanda did not disclose “obtaining RNA from a sample to produce an RNA sample comprising naturally-occurring RNAs.” Ans. 6. The Examiner found that Namsaraev supplied this element and thus rendered the claimed method obvious. Id. at 6–7. As stated in In re Oetiker, 977 F.2d 1443, 1445 (Fed. Cir. 1992): “[T]he examiner bears the initial burden . . . of presenting a prima facie case of unpatentability.” We have reviewed the arguments in Appellant’s Brief and Reply Brief, as well as the Examiner’s position as set forth in the Examiner’s Answer and Office Action.7 Based on our review, we have determined that the Examiner has not carried the burden of establishing that the claimed invention would have been obvious over the cited art. This case turns on whether the ordinary artisan would reasonably have expected success in practicing the method recited in the pending claims. Appellant argues that “in order to satisfy the expectation of success prong of 7 Office Action mailed June 13, 2017 (“Office Action.”). Appeal 2018-006629 Application 13/829,489 5 the analysis, one of ordinary skill in the art would have to recognize that PBCV-1 ligase could splint DNA molecules together using an RNA splint.” App. Br. 7. Appellant contends that the ordinary artisan would not have expected to be able to use PBCV-1 ligase to splint DNA molecules together using an RNA splint because Sriskanda discloses that “PBCV-1 DNA ligase . . . cannot ligate a nicked duplex composed of two DNAs annealed on an RNA template.” Id. at Abstract; see also, id. at 3549 (“PBCV-1 ligase . . . cannot ligate DNA molecules annealed to an RNA template.”). The Examiner finds a reasonable expectation of success based on the principle that prior art references are presumed enabled. Ans. 13–14. The Examiner concludes that because Sriskanda is practicing the same active method steps as claimed, and Sriskanda’s method is presumed to be enabled, the claimed invention would have been obvious. Id. The Examiner further asserts that “[i]f Sriskanda’s teachings indicate it is impossible to ligate DNA using an RNA-splint then applicant’s own claimed invention is not enabled.” Ans. 14. Although the Examiner’s logic would ordinarily be sound, in this case it does not sufficiently account for the unusual fact that the claimed method is taught in the prior art not to work. See, Sriskanda Abstract (“PBCV-1 DNA ligase . . . cannot ligate a nicked duplex composed of two DNAs annealed on an RNA template”). We find that the legal presumption of enablement for Sriskanda’s method of ligating DNA on an RNA template using PBCV-1 DNA ligase, see, In re Antor Media Corp., 689 F.3d 1282, 1287–88 (Fed. Cir. 2012), is rebutted by Sriskanda’s express teaching that this method does not work. Absent evidence that the skilled artisan would have an alternative basis for expecting success, or reason to doubt Appeal 2018-006629 Application 13/829,489 6 Sriskanda’s teaching that its method didn’t work, we find that the cited references do not provide the ordinary artisan a reasonable expectation that the claimed method would be successful. Accordingly, we reverse the Examiner’s rejection of claims 16, 20, 21, 23–28, and 34 as obvious over Sriskanda, Ho, and Namsaraev. OBVIOUSNESS OVER SRISKANDA, HO, NAMSARAEV, NILSSON, AND NILSSON 2 In rejecting claims 29–31 and 33 over the combination of Sriskanda, Ho, Namsaraev, Nilsson, and Nilsson 2, the Examiner applied the art as discussed above. Ans. 8. The Examiner relied upon Nilsson and Nilsson 2 to address the additional elements recited in dependent claim 29–31 and 33 rather than to address the concern that Sriskanda suggests the claimed method does not work. Accordingly, we reverse the Examiner’s rejection of claims 29–31 and 33 for the reasons discussed in above. OBVIOUSNESS OVER NAMSARAEV AND HO In rejecting claims 16, 20, 21, 23–30, and 34 as obvious over the combination of Namsaraev and Ho, the Examiner found that Namasaraev disclosed ligation of DNA to an RNA strand. Ans. 9. The Examiner acknowledged that Namsaraev did not disclose the use of PBCV-1 ligase, but found that Ho characterized PBCV-1 and disclosed its use in ligating two DNA polynucleotides using a DNA splint. Id. at 10. The Examiner concluded that it would have been obvious to use PBCV-1 ligase in Namsaraev’s method of ligating DNA to an RNA splint based on the desire to “try and not only utilize but optimize other ligases for use with an RNA splint.” Id. at 11. Appeal 2018-006629 Application 13/829,489 7 We have reviewed the arguments in Appellant’s Brief and Reply Brief, as well as the Examiner’s position as set forth in the Examiner’s Answer and Office Action. Based on our review, we have determined that the Examiner has not carried the burden of establishing that the claimed invention would have been obvious over the cited art. As the Examiner appears to acknowledge (Ans. 17–19), that the Examiner did not include Sriskanda in this rejection does not change the fact that the ordinary artisan would have been aware of its teachings. For the reasons discussed above, we find that the disclosure in Sriskanda that “PBCV-1 DNA ligase . . . cannot ligate a nicked duplex composed of two DNAs annealed on an RNA template” (Sriskanda Abstract), would have deprived the ordinary artisan of a reasonable expectation of success in arriving at the claimed invention based on the cited prior art. The Examiner does not identify in Namsaraev or Ho, and we do not find, a basis for expecting that PBCV-1 DNA ligase could be used successfully as claimed notwithstanding Sriskanda’s teaching that the claimed method didn’t work. Accordingly, we reverse the Examiner’s rejection of claims 16, 20, 21, 23– 30, and 34 as obvious over the combination of Namsaraev and Ho. OBVIOUSNESS OVER NAMSARAEV, HO, NILSSON, AND NILSSON2 In rejecting claims 30 and 31 over the combination of Namsaraev, Ho, Nilsson, and Nilsson 2, the Examiner applied the art as discussed above. Ans. 12. The Examiner relied upon Nilsson and Nilsson 2 to address the additional elements recited in dependent claim 30 and 31 rather than to address the concern that Sriskanda suggests the claimed method does not Appeal 2018-006629 Application 13/829,489 8 work. Accordingly, we reverse the Examiner’s rejection of claims 30 and 31 for the reasons discussed in above. CONCLUSION In summary: Claims Rejected 35 U.S.C. § Basis Affirmed Reversed 16, 20, 21, 23– 28, 34 103(a) Sriskanda, Ho, and Namsaraev 16, 20, 21, 23–28, 34 29–31, 33 103(a) Sriskanda, Ho, Namsaraev, Nilsson, and Nilsson 2 29–31, 33 16, 20, 21, 23– 30, 34 103(a) Namsaraev and Ho 16, 20, 21, 23–30, 34 30, 31 103(a) Namsaraev, Ho, Nilsson, and Nilsson 2 30, 31 Overall Outcome 16, 20, 21, 23–31, 33, 34 REVERSED Copy with citationCopy as parenthetical citation