Ryo Kubota et al.

Patent Trials and Appeals Board

Jan 14, 2022

2021002410 (P.T.A.B. Jan. 14, 2022)

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. 13/805,578 03/07/2013 Ryo Kubota 140110.00101 4327 109330 7590 01/14/2022 Pepper Hamilton LLP/Diagenetix 400 Berwyn Park 899 Cassatt Road Berwyn, PA 19312 EXAMINER CHUNDURU, SURYAPRABHA ART UNIT PAPER NUMBER 1637 NOTIFICATION DATE DELIVERY MODE 01/14/2022 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): bwdocket@pepperlaw.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte RYO KUBOTO and DANIEL M. JENKINS Appeal 2021-002410 Application 13/805,578 Technology Center 1600 BEFORE JEFFREY N. FREDMAN, JOHN E. SCHNEIDER, and RACHEL H. TOWNSEND, Administrative Patent Judges. SCHNEIDER, Administrative Patent Judge. DECISION ON APPEAL STATEMENT OF THE CASE Pursuant to 35 U.S.C. § 134(a), Appellant1 appeals from the Examiner’s decision to reject claims 1-4, 6, 7, 9 and 17-23. We have jurisdiction under 35 U.S.C. § 6(b). We AFFIRM. 1 We use the word Appellant to refer to “applicant” as defined in 37 C.F.R. § 1.42(a). Appellant identifies the real parties in interest as the University of Hawaii and Diagenetix, Inc. Appeal Br. 2. Appeal 2021-002410 Application 13/805,578 2 CLAIMED SUBJECT MATTER The claims are directed to sequence specific real-time monitoring or LOOP-mediated isothermal amplification (LAMP). Claim 1, reproduced below, is illustrative of the claimed subject matter: 1. A method of monitoring LOOP-mediated isothermal amplification (LAMP) of a target DNA, comprising: contacting an assimilating probe and a DNA polymerase with a LAMP reaction mixture under conditions sufficient to amplify the target DNA, wherein the LAMP reaction mixture comprises the target DNA and one or more LAMP primers that hybridize with the target DNA, wherein the assimilating probe comprises a pair of labeled oligonucleotide probes, wherein the pair of labeled oligonucleotide probes comprises a first oligonucleotide strand and a second oligonucleotide strand, wherein the first oligonucleotide strand comprises a quencher probe at a 3' end, wherein the second oligonucleotide strand of the assimilating probe comprises a fluorophore at a 5' end; wherein the ratio of the amount of the second oligonucleotide strand to the amount of the first oligonucleotide strand is less than 1:1; and measuring fluorescence emitted by the LAMP reaction mixture that has been contacted with the assimilating probe and the DNA polymerase, wherein the concentration of the DNA polymerase is greater than or equal to 8U. REFERENCES The prior art relied upon by the Examiner is: Appeal 2021-002410 Application 13/805,578 3 Name Reference Date Nadeau US 2012/0276538 A1 Nov. 1, 2012 Uematsu et al. EP 2071041 A1 June 17, 2009 Li et al., A new class of homogeneous nucleic acid probes based on specific displacement hybridization, 30 Nucleic Acids Research 1 (2002) REJECTIONS The Examiner has rejected the pending claims as follows: Claims 1-4, 6, 7, 9, and 17-23 have been rejected under 35 U.S.C. § 103(a) as unpatentable over Uematsu in view of Li. Claims 1-4, 6, 7, 9, and 17-23 have been rejected under 35 U.S.C. § 103(a) as unpatentable over Nadeau in view of Li. OPINION Uematsu Combined with Li Issue The issue with respect to this rejection is whether a preponderance of the evidence supports the Examiner’s conclusion that the subject matter of claims 1-4, 6, 7, 9, and 17-23 would have been obvious to one of ordinary skill in the art at the time the invention was made over Uematsu combined with Li. The Examiner finds Uematsu et al. teach a method of claim 1, 19-21, monitoring loop-mediated isothermal amplification (LAMP) of a target DNA and detecting the presence or absence of the target comprising: contacting one or more assimilating probes and a DNA polymerase with a LAMP reaction mixture comprising the target and one or more LAMP primers, wherein the assimilating probe comprises a pair of labeled probes wherein the probes comprise a first oligonucleotide strand and a Appeal 2021-002410 Application 13/805,578 4 second strand, wherein the first oligonucleotide comprises a quencher at 3' end and the second oligonucleotide strand comprises a fluorophore at 5 ' end, measuring fluorescence emitted by the LAMP reaction mixture that has been contacted with the assimilating probe and 8U of DNA polymerase and detecting the presence or absence of the target (see entire document, at least para 0007-0013, 0016, 0019, 0023-0033, 0035-0045; indicating loop mediated isothermal amplification using one or more primer pairs and a probe set comprising a first and a second probe strands having , each strand comprising quencher or fluorophore). Final Act. 4. The Examiner finds that Uematsu does not teach a ratio of first strand to second strand of less than 1:1 but that Li teaches this limitation. Id. at 5-6. The Examiner concludes It would be a prima facie obvious to one of the ordinary person skilled in the art at the time the invention was made, to modify the method as taught by Uematsu et al. with the amount of double-stranded probes as taught by Li et al. to develop an improved method for sequence specific detection of target nucleic acid. The ordinary person skilled in the art would have motivated to combine the references to have a reasonable expectation of success that the combination would result in enhancing the specificity of discriminating sequence variation in a target nucleic acid because both references teach use of double stranded probes having fluorophore and quencher labels and Li et al. specifically taught use of an amount of the second strand to the first strand less than 1 :1 would enhance the specificity of the probes in discriminating perfectly matched and mismatched target nucleic acid and such a combination is considered obvious over the cited prior art. . Further, As noted in In re Aller, 105 USPQ 233 at 235. More particularly, where the general conditions of a claim are disclosed in the prior art (Li et al.), it is not inventive to discover the optimum or workable ranges by routine experimentation. Routine optimization is not considered inventive and no evidence has Appeal 2021-002410 Application 13/805,578 5 been presented that the selection of hybridization conditions performed was other than routine, that the products resulting from the optimization have any unexpected properties, or that the results should be considered unexpected in any way as compared to the closest prior art. Id. at 6. Appellant contends that the Examiner has not established that one skilled in the art would have been motivated to combine the teachings of the references. Appeal Br. 8. Appellant contends that Uematsu teaches that not all probes are equivalent and that certain probes used in PCR cannot be used in LAMP. Id. at 9. Appellant contends that one probe cannot be easily substituted for another. Id. Appellant contends that Li teaches that the probe taught therein is for a PCR process and not LAMP. Id. Appellant contends that Li teaches that the probes can only hybridize at certain temperatures and that one skilled in the art would not expect them to work at the temperatures of the LAMP process. Id. Appellant contends that the Examiner has failed to adequately explain why one skilled in the art would have had a reasonable expectation of success in performing the presently claimed method. Appellant also contends that there is evidence of unexpected results sufficient to rebut the Examiner’s prima facie case of obviousness. Id. at 10- 11. Appellant contends that the data in the Specification shows that at ratio of first to second stands of less than 1:1 produces better results. Id. at 10. Analysis We adopt the Examiner’s findings of fact, reasoning on scope and content of the prior art, and conclusions set out in the Final Action and Answer regarding this rejection. We find the Examiner has established a Appeal 2021-002410 Application 13/805,578 6 prima facie showing that the subject matter of the claims would have been obvious over Uematsu combined with Li to a person of ordinary skill in the art. Appellant has not produced evidence showing, or persuasively argued, that the Examiner’s determinations on obviousness are incorrect. Only those arguments made by Appellant in the Brief have been considered in this Decision. Arguments not presented in the Brief are waived. See 37 C.F.R. § 41.37(c)(1)(iv) (2015). We have identified claim 1 as representative; therefore, all claims fall with claim 1. We address Appellant’s arguments below. Appellant contends that the Examiner has not establish a proper motivation to combine the teachings of Li with those of Uematsu nor has the Examiner shown that one skilled in the art would have had a reasonable expectation of success in combining the references. Appeal Br. 8-10. Appellant contends that Uematsu makes it clear that not all probes are equivalent and that they cannot always work in all systems. Id. at 9, Appellant points to the passage in Uematsu where it teaches that probes useful in the “TaqMan” system are not suitable for use in a LAMP system. Id. (quoting Uematsu ¶ 3). Appellant contends that the probes in Li are designed for use in a PCR system where the temperature cycled is from high to low. Id. Appellant contends that one skilled in the art would not use such a probe in a LAMP system where the temperature is constant. Id. We are not persuaded by this argument. As the Examiner points out, Uematsu teaches the use of a double-stranded probe in a LAMP system. Ans. 10. The Examiner also points out that Li tested the disclosed probes under isothermal conditions. Ans. 10. Moreover, Li teaches the probes Appeal 2021-002410 Application 13/805,578 7 taught therein “exhibit potentially greater specificity and sensitivity than molecular beacons and may extend their use in single mutation detection to both PCR and isothermal amplification systems.” Li 7. We agree with the Examiner that one skilled in the art would have been motivated to combine the teachings of the references and would have had a reasonable expectation of success in applying these probes to the isothermal LAMP system based on the express teaching of Li that the probes may be used in isothermal amplification systems. Appellant contends that there is evidence of unexpected results in the record to support a finding of non-obviousness. Appellant contends that the data in the Specification shows that the use of a ratio of fluorescent probes to quencher probes of less than 1:1 prevents inhibition of the LAMP reaction and reduces “background fluorescence confounding detection.” Appeal Br. 11 citing Spec. ¶ 76. Appellant contends that this result is unexpected. Id. We have considered Appellant’s argument and the data in the Specification and are not persuaded that there is evidence of unexpected results that when considered together with the evidence of obviousness is sufficient to overcome the Examiner’s prima facie case of obviousness. We discern nothing in the present Specification or the present record, other than the argument in the Brief that the results reported in the Specification are unexpected. “[B]y definition, any superior property must be unexpected to be considered evidence of non-obviousness. Thus, in order to properly evaluate whether a superior property was unexpected, the [fact-finder] should have considered what properties were expected. Here, [the] evidence must fail because the record is devoid of any evidence of what the skilled artisan would have expected.” Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348, Appeal 2021-002410 Application 13/805,578 8 1371 (Fed. Cir. 2007). Attorney argument is not evidence. Johnston v. IVAC Corp., 885 F.2d 1574, 1581 (Fed. Cir. 1989). Moreover, as the Examiner points out, the ratio of the amount of the second oligonucleotide strand to the amount of the first oligonucleotide strand is less than 1:1 whereas the data cited by Appellant is based on a ratio of approximately 1:1. Ans. 11. Thus, the results are not commensurate with the claims. “The evidence presented to rebut a prima facie case of obviousness must be commensurate in scope with the claims to which it pertains.” In re Dill, 604 F.2d 1356, 1361 (CCPA 1979). Indeed, the data is not related to the claim scope and therefore fails to establish unexpected results. Conclusion Based on the foregoing we conclude that a preponderance of the evidence supports the Examiner’s conclusion that the subject matter of claims 1-4, 6, 7, 9, and 17-23 would have been obvious to one of ordinary skill in the art at the time the invention was made over Uematsu combined with Li. We also find that the asserted unexpected results, when balanced with the prima facie case of obviousness, are not sufficient to demonstrate non-obviousness of the claims. Nadeau Combined with Li Appellant has offered no arguments with respect to this rejection. See Appeal Br. 6-11; Ans. 12-13. Therefore, we summarily affirm this rejection. CONCLUSION The Examiner’s rejections are affirmed. More specifically, The rejection of claims 1-4, 6, 7, 9, and 17-23 under 35 U.S.C. Appeal 2021-002410 Application 13/805,578 9 § 103(a) as unpatentable over Uematsu in view of Li is affirmed. The rejection of claims 1-4, 6, 7, 9, and 17-23 under 35 U.S.C. § 103(a) as unpatentable over Nadeau in view of Li is affirmed. DECISION SUMMARY In summary: Claims Rejected 35 U.S.C. § Reference(s)/Basis Affirmed Reversed 1-4, 6, 7, 9, 17-23 103(a) Uematsu, Li 1-4, 6, 7, 9, 17-23 1-4, 6, 7, 9, 17-23 103(a) Nadeau, Li 1-4, 6, 7, 9, 17-23 Overall Outcome 1-4, 6, 7, 9, 17-23 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. § 1.136(a). See 37 C.F.R. § 1.136(a)(1)(iv). AFFIRMED