Eiken Kagaku Kabushiki KaishaDownload PDFPatent Trials and Appeals BoardDec 3, 20212021000598 (P.T.A.B. Dec. 3, 2021) 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. 15/537,121 06/16/2017 Satoru Michiyuki 046124-5451 8226 9629 7590 12/03/2021 Morgan, Lewis & Bockius LLP (WA) 1111 Pennsylvania Avenue, N.W. Washington, DC 20004 EXAMINER SISSON, BRADLEY L ART UNIT PAPER NUMBER 1634 NOTIFICATION DATE DELIVERY MODE 12/03/2021 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): karen.catalano@morganlewis.com patents@morganlewis.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte SATORU MICHIYUKI Appeal 2021-000598 Application 15/537,121 Technology Center 1600 Before JEFFREY N. FREDMAN, TIMOTHY G. MAJORS, and RACHEL H. TOWNSEND, Administrative Patent Judges. TOWNSEND, Administrative Patent Judge. DECISION ON APPEAL Pursuant to 35 U.S.C. § 134(a), Appellant1 appeals from the Examiner’s decision to reject claims to a probe for single nucleotide polymorphism detection and a method of its use. We have jurisdiction under 35 U.S.C. § 6(b). We Affirm In Part. 1 We use the word Appellant to refer to “applicant” as defined in 37 C.F.R. § 1.42. Appellant identifies the real party in interest as Eiken Kagaku Kabushiki Kaisha. (Appeal Br. 1.) Appeal 2021-000598 Application 15/537,121 2 STATEMENT OF THE CASE Appellant’s Specification explains that “a polymorphism caused by replacement of one base in a [nucleotide] sequence is particularly designated as a single nucleotide polymorphism [SNP].” (Spec. ¶ 3.) The appearance frequency of SNPs “is the highest among those of mutations found in the human genome.” (Id.) Appellant’s Specification explains that “[v]arious detection methods and detection probes for the SNP have been developed so far,” including “a fluorescence labeled probe method.” (Id. ¶ 5.) “In this method, it is determined whether or not the SNP is present in a sequence of a target nucleic acid depending on a difference in the hybridization efficiency attained when a fluorescence labeled probe is perfectly matched or mismatched with the target nucleic acid.” (Id.) “[F]luorescence labeled probe[s] comprising a region for detecting the SNP, a region for recognizing a sequence in the vicinity of the SNP and a region for connecting these two regions to each other ha[ve] been developed.” (Id.) For example, the Specification describes the following prior art probes: an oligonucleotide comprising: a switch domain comprising (a) a nucleic acid region complementary to a first sequence of nucleic acid residues of a target nucleic acid and (b) at least one cross-linking domain and at least one binding domain, in which the switch domain is capable of distinguishing (i) a second sequence of the nucleic acid residues of the target nucleic acid complementary to the binding domain from (ii) a second sequence of the nucleic acid residues of the target nucleic acid comprising at least one nucleic acid residue not complementary to the binding domain under a condition where the region (a) forms a stable double strand together with the first sequence of the nucleic acid residues of the target nucleic acid. Appeal 2021-000598 Application 15/537,121 3 (Id. ¶¶ 6, 8 (citing Japanese Unexamined Patent Publication No. 2006- 525027).) The “cross-linking domain comprises a universal base, a non- hydrogen bonding natural base or an analog of any of these, or a mixture of a universal base and a non-hydrogen bonding natural base or an analog of any of these.” (Id.) The Specification also describes the following prior art probes: a detectably labeled probe, comprising an anchor nucleic acid domain and a reporter nucleic acid domain, in which the anchor and reporter domains are linked to each other via a non- nucleoside linker, neither the anchor domain nor the reporter domain forms a stem loop in the absence of a target nucleic acid, (i) the probe is not extended by polymerase, (ii) the linker is bound to the anchor domain within two nucleotides at the 3'- end of the anchor domain, and is bound to the reporter domain within two nucleotides at the 5'-end of reporter domain, and the anchor domain is not bound to a detectable label. (Id. ¶¶ 7, 8 (citing Japanese Unexamined Patent Publication No. 2013- 501508).) The Specification identifies the following problems with the prior art probes just described. (Id. ¶ 9.) In particular, it is stated that where the cross-linking domain is required to have a universal base of the like for forming a prescribed structure, the problem is “that it lacks flexibility with respect to probe design, and in addition, . . . it is more expensive than a case where usual bases alone are used in the oligonucleotide synthesis.” (Id.) And, where the probe includes a non-nucleotide linker, the problem is that “it is necessary to prepare the linker separately from the anchor nucleic acid domain and the reporter nucleic acid domain, and to synthesize these thereafter,. . . [which] synthesis of the probe is troublesome.” (Id.) Appellant’s invention is directed to a probe for detecting SNPs that is different from the foregoing designs. (Id. ¶¶ 10–11.) Appeal 2021-000598 Application 15/537,121 4 Claims 1–13 and 20–29 are on appeal. Claim 1, reproduced below, is illustrative of the claimed subject matter: 1. A probe for single nucleotide polymorphism detection to be used for a target nucleic acid sequence where a single nucleotide polymorphism is present, wherein the target nucleic acid sequence comprises a first target sequence corresponding to a region comprising the single nucleotide polymorphism, and a second target sequence positioned on a 3' or 5' side of the first target sequence and corresponding to a region without the single nucleotide polymorphism, the probe comprises a reporter region for detecting the single nucleotide polymorphism, an anchor region, and a linker region, the reporter region comprises nucleotides consisting of a sequence perfectly matching with the first target sequence when a nucleotide of the single nucleotide polymorphism is a first nucleotide, and mismatching with the first target sequence when the nucleotide is a nucleotide other than the first nucleotide; and a fluorescent dye quenching when the first target sequence and the reporter region hybridize, the anchor region comprises nucleotides consisting of a sequence complementary to the second target sequence, and the linker region links the reporter region and the anchor region to each other, and comprises nucleotides consisting of a sequence non-complementary to a sequence between the first target sequence and the second target sequence in the target nucleic acid sequence. (Appeal Br. Appendix A: Claims, A1) Appeal 2021-000598 Application 15/537,121 5 The prior art relied upon by the Examiner is: Name Reference Date Hirai et al. US 2009/0176231 A1 July 9, 2009 Chun et al. US 2012/0220468 A1 Aug. 30, 2012 Wangh et al. US 2013/0295570 A1 Nov. 7, 2013 Cobb US 2014/0227683 A1 Aug. 14, 2014 DISCUSSION The Examiner found that Cobb teaches probes and methods for their use in detecting polymorphisms, and that in one embodiment, the probe includes a reporter and an anchor sequence which are separated from each other by a linker sequence. (Final Action 31 (citing Cobb Abstr.).) The Examiner found that polymorphism “is deemed to fairly suggest detection of single nucleotide polymorphisms.” (Id.) The Examiner found that, in fact, Cobb teaches that a probe with a reporter “is used to report the presence of a specific sequence or sequence variants (eg, SNPs, insertions, deletions, etc.).” (Ans. 14 (citing Cobb ¶ 80).) The Examiner further found that Cobb teaches the reporter sequence includes a label, such as a fluorescent label. (Final Action 31 (citing Cobb ¶ 17).) The Examiner found that Cobb does not specifically teach using a fluorescent label that is quenched upon binding/hybridization (id.), but “is deemed to provide a variety of options as to how the probe can be designed and used” (Ans. 14). In particular, the Examiner noted that Cobb teaches that nucleic acid probes that include first and second regions where a quencher molecule is included in one of the regions and the other region includes a reporter molecule were known in the art. (Ans. 6 (citing Cobb Appeal 2021-000598 Application 15/537,121 6 ¶ 6).) The Examiner further found that Cobb includes a dependent claim (claim 6) that states as its only further limitation of independent claim 1 that “the probe does not comprise a quencher moiety.” (Id. at 13.) Thus, the Examiner concluded that claim 1 of Cobb necessarily embodies a probe that includes a quencher moiety or that does not include a quencher moiety. (Id.) In addition, the Examiner found that Hirai teaches using labeled quenching probes, including guanine quenching probes, which “is known as so-called QProbe.” (Final Action 33 (citing Hirai ¶ 32).) The Examiner also found that Hirai teaches the advantage of using such a guanine quenching probe: “The use of such a probe makes it possible to verify hybridization and dissociation easily according to a change in the signal.” (Id.) The Examiner further found that Hirai teaches using labeled probes for detection of single nucleotide polymorphisms. (Id. (citing Hirai ¶¶ 2, 21).) Lastly, the Examiner found that Applicant’s Specification admits to a number of specific examples of fluorescent dyes that are “comprised in the QProbe.” (Final Action 34 (citing Spec. ¶ 34).) The Examiner concluded from the foregoing teachings that it would have been obvious to modify the Cobb probe label with the commercially-available fluorescent dyes that are quenched upon hybridization of probe to target for in using same, one only has to use one label, not both fluorophore and quencher. By using only one, and that which is commercially available, the amount of time and resources involved in producing labeled probes is effectively cut in half. (Final Action 34.) With respect to the linker required by dependent claims 3, 4, 7–9, 11, and 12, the Examiner stated Cobb “has not been found to teach that the linker does not comprise a universal base, or that it can be but only one kind Appeal 2021-000598 Application 15/537,121 7 of base.” (Final Action 32.) However, the Examiner concluded that such would have been obvious from the teachings of Chun. (Id.) In particular, the Examiner found that Chun teaches a linker “which serves to link two probe sequences” “can be a poly(T)7 sequence.” (Id.) Obviousness: Claims 1, 5, 22, 25, 26, and 27 Appellant does not address the method claims separately from the composition claims. We select the composition of claim 1 as representative. We agree with the Examiner’s conclusion that claim 1 would have been obvious from the teachings of Cobb, Hirai, and the admitted prior art. In affirming a multiple reference rejection under 35 U.S.C. § 103, the Board may rely on fewer than all of the references relied on by the Examiner in an obviousness rationale without designating it as a new ground of rejection. In re Bush, 296 F.2d 491, 496 (CCPA 1961). Thus, that we do not rely on the teachings of Chun to affirm the Examiner does not require that we designate the rejection as a new ground. Appellant argues that “[a] critical feature of the claims is fluorescence dye quenching when the first target sequence and the reporter region hybridize to the target nucleic acid” and that Cobb teaches away from quenching. (Appeal Br. 14 (citing Cobb ¶ 17).) We do not find this argument persuasive for the reasons articulated by the Examiner in the Answer. (Ans. 13–14.) As the Examiner explained, paragraph 17 of Cobb merely indicates a preference to not use a quencher. There is no discussion as to why the known quenchers of the prior art (see Cobb ¶ 6) and the well- known technique of using quenching in target sequence detection would not work in the Cobb system. “[A] patentee preferably omits from the Appeal 2021-000598 Application 15/537,121 8 disclosure any routine technology that is well known at the time of application.” Chiron Corp. v. Genentech Inc., 363 F.3d 1247, 1254 (Fed. Cir. 2004). And Hirai, a reference that predates Cobb, demonstrates that fluorescent quenching probes, indeed QProbes, were known in the art well prior to Cobb’s filing date. Thus, we do not find persuasive of error, Appellant’s argument that Cobb does not provide an exemplification of a probe with a quencher (Reply Br. 2). Moreover, we agree with the Examiner’s claim differentiation argument in light of the foregoing, and we do not find persuasive Appellant’s argument that the Examiner has improperly “expand[ed] the scope and contents of the prior art” (Reply Br. 2) or suggested a modification that is unintended (Appeal Br. 18). Dependent claim 6 of Cobb recites that the probe does not include a quencher and that is the only difference from claim 1. Thus, claim 1 is reasonably understood to embrace a probe that includes a quencher. For the foregoing reasons, we affirm the Examiner’s rejection of claims 1, 6, and 25 as being obvious from Cobb and Hirai. Appellant does not argue claims 5, 22, or 27 separately. Thus, these claims fall with claim 1. 37 C.F.R. § 41.37(c)(1)(iv). Appellant also does not separately argue the rejection of claim 26, where the Examiner added Wangh to address the obviousness of the limitations recited in that claim. Thus, we summarily affirm the Examiner’s rejection of claim 26 as being obvious over Cobb, Hirai, and Wangh. Hyatt v. Dudas, 551 F.3d 1307, 1314 (Fed. Cir. 2008) (“When the appellant fails to contest a ground of rejection to the Board, . . . the Board may treat any argument with respect to that ground of rejection as waived.”) Appeal 2021-000598 Application 15/537,121 9 Obviousness: Claims 2, 10, and 13 Regarding claim 2’s requirement that the length of the nucleotide sequence of the reporter region is shorter than a length of the nucleotide sequence of the anchor region, the Examiner found that Cobb teaches a variety of nucleotide lengths for the anchor region, e.g., between 20 and 200 nucleotides, and a variety of lengths for the reporter region, e.g., between 15 and 200 nucleotides, and that a number of the identified anchor region lengths are longer than the identified reporter region lengths. (Final Action 32.) In particular, the Examiner noted the following teachings about the anchor length from Cobb: The anchor region is preferably at least 50 nt in length, more preferably at least 60, 70, 80, 90, 100, 125, 150 nt. The anchor region is preferably no more than 200 nt in length and no less than 20 nt in length. (Id. (citing Cobb ¶ 26).) The Examiner noted the following teachings about the reporter length from Cobb: The reporter region is preferably 15-200 nt in length, more preferably 15-150, more preferably still 15-100, or 20-100, 30- 80, 40-60, or around 50 nt in length. (Id. (citing Cobb ¶ 18).) Accordingly, the Examiner concluded that Cobb discloses the limitation that the anchor sequence is longer than the reporter sequence. (Id.) We agree with the Examiner’s conclusion of obviousness. The relevant paragraphs of Cobb are set forth above. Those paragraphs indicate, for example, an anchor length could be selected to be 125 or 150 nucleotides, and a reporter region could be a nucleotide length of “15-100, or 20-100, 30-80, 50-60 or around 50.” (Cobb ¶¶ 18, 26.) As such the anchor length being longer than the reporter region is a probe possibility Appeal 2021-000598 Application 15/537,121 10 reasonably suggested by Cobb’s teachings. And for this reason, we do not agree with Appellant that Cobb “does not disclose . . . the feature that reporter region is shorter than the anchor region.” (Appeal Br. 15.) Consequently, we affirm the Examiner’s rejection of claim 2 (and claim 13 which has the same requirements as claim 2) as being obvious from the teachings of Cobb and Hirai. Appellant does not argue claim 10, which depends from claim 2 separately. Thus, claim 10 falls with claim 2. 37 C.F.R. § 41.37(c)(1)(iv). Obviousness: Claims 23 and 24 Regarding the requirement that the fluorescent dye is selected from a particular group of dyes, the Examiner noted that Appellant’s Specification admits that the fluorescent dyes named in the claims that quench on hybridization were known and commercially available “in the QProbe” series manufactured by Nippon Steel & Sumikin Eco-Tech Corporation. (Final Action 34 (citing Spec. ¶ 34).) The Examiner concluded that it would have been obvious to use such commercially available dyes in the Cobb probe and in light of the teachings of Hirai. (Id.) The Examiner stated: It would have also been obvious to one off ordinary skill in the art to have employed the commercially-available fluorescent dyes that are quenched upon hybridization of probe to target for in using same, one only has to use one label, not both fluorophore and quencher. By using only one, and that which is commercially available, the amount of time and resources involved in producing labeled probes is effectively cut in half. (Id.) Appeal 2021-000598 Application 15/537,121 11 We agree with the Examiner’s conclusion that the Specification is an admission that the fluorescent dyes of claims 23 and 24 were commercially available and known to be used with the QProbe series. Appellant argues that the Specification statement is not an admission that the fluorescent dyes are commercially available, just that the QProbe reagent is commercially available. (Appeal Br. 4–5.) We do not find this argument persuasive. The attorney argument in the Appeal Brief that the Specification’s statement is not an admission that the fluorescent dyes are commercially available is not evidence. Icon Health & Fitness v. Strava Inc., 849 F.3d 1034, 1043 (Fed. Cir. 2017); see also, Gemtron Corp. v. Saint-Gobain Corp., 572 F.3d 1371, 1380 (Fed. Cir. 2009) (“[U]nsworn attorney argument . . . is not evidence and cannot rebut . . . other admitted evidence . . . .”) The Specification clearly states that “Examples of the fluorescent dye having such a characteristic [that quenches when the first target sequence and the reporter region hybridize] include QProbe series (manufactured by Nippon Steel & Sumikin Eco-Tech Corporation).” (Spec. ¶ 34.) In other words, the Specification states that a fluorescent dye is included in the QProbe series that are commercially available. And the Specification states “Specific examples of the fluorescent dye comprised in the QProbe include FITC, TMR, 6-joe, Bodipy-FL/C6 and Bodipy-FL/C3.” (Id.) Indeed, the Specification admission appears consistent with the teachings of Hirai. In particular, Hirai teaches a number of commercially available dyes that can be used with QProbe, including Bodipy-FL, TAMRA, and FAM. (Hirai ¶¶ 32–33). Appeal 2021-000598 Application 15/537,121 12 Thus, we affirm the Examiner’s rejection of claims 23 and 24 as being obvious from the teachings of Cobb, Hirai, and the admitted evidence at paragraph 34 of the Specification. Non-Obviousness: Claims 3, 4, 7, 8, 9, 11, 12, 20, 21, 28, and 29 The Examiner relied on the teachings of Chun to address the obviousness of the requirement of claim 3 that the linker region does not include a universal base, and claim 4, that the linker region consists of only one kind of base selected from adenine, guanine, cytosine, and thymine. (See Final Action 32; Ans. 15–16.) We do not affirm the Examiner’s rejection for the reasons expressly noted by Appellant in the Appeal Brief. (See Appeal Br. 15–16.) Chun’s specified linker sequence that can be a poly(T)7 sequence is not a linker between two probe sequences, but is used to link a probe to a substrate. (See, e.g., Chun Figures 5A–7, ¶¶ 156, 409.) The linker that separates hybridization portions of the probe from each other is the sequence Y’q. (Id. ¶ 36.) And Chun explains that the linker between probe sections is “at least three universal bases.” (Id.) Thus, given the art of record relied on by the Examiner, we cannot agree that a prima facie case of obviousness has been established with respect to the requirements of dependent claims 3 and 4, which are also requirements of claims 7, 8, 9, 11, 12, 20, 21, 28, and 29. Consequently, we reverse the Examiner’s rejection of claims 3, 4, 7, 8, 9, 11, 12, 20, 21, 28, and 29 as being obvious from the teachings of Cobb, Chun, Hirai, and the admitted prior art. Appeal 2021-000598 Application 15/537,121 13 DECISION SUMMARY In summary: Claims Rejected 35 U.S.C. § Reference(s)/Basis Affirmed Reversed 1–13, 20– 25, 27, 28 103 Cobb, Chun, Hirai, Admitted Prior Art 1, 2, 5, 6, 10, 13, 22, 23, 24, 25, 27 3, 4, 7–9, 11, 12, 20, 21, 28 26, 29 103 Cobb, Chun, Hirai, Admitted Prior Art, Wangh 26 29 Overall Outcome 1, 2, 5, 6, 10, 13, 22, 23, 24, 25– 27 3, 4, 7–9, 11, 12, 20, 21, 28, 29 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 IN PART Copy with citationCopy as parenthetical citation