Robert TerbrueggenDownload PDFPatent Trials and Appeals BoardApr 1, 202011801990 - (D) (P.T.A.B. Apr. 1, 2020) 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. 11/801,990 05/10/2007 Robert Terbrueggen 068433-5001-US 5506 67374 7590 04/01/2020 MORGAN, LEWIS & BOCKIUS LLP (SP) ONE MARKET, SPEAR STREET TOWER, SUITE 2800 SAN FRANCISCO, CA 94105 EXAMINER SISSON, BRADLEY L ART UNIT PAPER NUMBER 1634 NOTIFICATION DATE DELIVERY MODE 04/01/2020 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): DONALD.MIXON@MORGANLEWIS.COM SFIPDOCKETING@MORGANLEWIS.COM PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte ROBERT TERBRUEGGEN Appeal 2018-004820 Application 11/801,990 Technology Center 1600 Before RICHARD J. SMITH, TAWEN CHANG, and DEVON ZASTROW NEWMAN, Administrative Patent Judges. CHANG, Administrative Patent Judge. DECISION ON APPEAL Pursuant to 35 U.S.C. § 134(a), Appellant1 appeals from the Examiner’s decision to reject claims 51–60. 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. Appellant identifies the real party in interest as DxTerity Diagnostics Incorporated. Appeal Br. 4. Appeal 2018-004820 Application 11/801,990 2 BACKGROUND The Specification explains that gene probe assays are useful in “identifying infectious organisms,” “probing the expression of normal and mutant genes and identifying mutant genes,” “typing tissue for compatibility preceding tissue transplantation,” “matching tissue or blood samples for forensic medicine,” and “exploring homology among genes from different species.” Spec. ¶ 4. According to the Specification, “a gene probe assay should be sensitive, specific and easily automatable.” Id. ¶ 5. The Specification states that “[t]he requirement for sensitivity . . . has been greatly alleviated by the development of . . . amplification technologies” such as PCR but that “[t]he drawback to such . . . technologies is their dependence on particular reagents, such as enzymes, which result in a need for subsequent purification procedures prior to detection.” Spec. ¶ 5. The Specification likewise states that “[s]pecificity also remains a problem in many currently available . . . gene probe assays” and that “[m]any of the nucleic acid detection methods in current use have characteristics and/or limitations that hinder their broad applicability or make them unsuitable for a given application.” Spec. ¶¶ 6, 15. For instance, the Specification explains that it is “generally very difficult using traditional technology” to “distinguish targets with perfect complementarity [to the probes] from targets with mismatches” and that DNA arrays, which have “gained increased prominence . . . especially for applications involving the simultaneous measurement of numerous nucleic acid targets,” require “many upstream processing steps prior to contacting the DNA array with the sample,” which can “significantly increase the time and cost of detecting a Appeal 2018-004820 Application 11/801,990 3 nucleic acid target(s) . . . and . . . have significant implications on the quality of the data obtained.” Id. ¶¶ 7, 14–16. The Specification states that “[n]ew experimental techniques with the necessary specificity for mismatch detection with standard probes include . . . DNA ligation assays where single point mismatches prevent ligation” and explains that “using ligation reactions to increase signal strength and improve specificity” is “[o]ne method for reducing upstream processing steps,” which “could significantly reduce the costs and improve the quality of results obtained from a DNA array based test.” Spec. ¶¶ 7, 16–17. The Specification also states that non-enzymatic methods are available for detecting sequence variations and that “[s]ome of the advantages of using non-enzymatic approaches for the nucleic acid target detection include lower sensitivity to non-natural DNA analog structures, ability to use RNA target sequences, lower cost and greater robustness under varied conditions.” Id. ¶¶ 8, 12. Further according to the Specification, “the present invention provides methods and composition for non-enzymatic chemical ligation reactions which greatly simplify the process of detecting and measuring nucleic acid targets.” Spec. ¶ 18. CLAIMED SUBJECT MATTER The claims are directed to a method for detecting the presence of a known target nucleic acid in a sample. Claim 51 is illustrative: 51. A method for detecting the presence of a known target nucleic acid in a sample comprising: a) providing a ligation substrate comprising: Appeal 2018-004820 Application 11/801,990 4 i) said known target nucleic acid comprising a first target domain and an adjacent second target domain, wherein the first target domain is upstream of the second target domain; ii) a first nucleic acid ligation probe comprising: 1) a first probe domain hybridized to said first target domain; and 2) a 5’-ligation moiety; and iii) a second nucleic acid ligation probe comprising: 1) a second probe domain hybridized to said second target domain; 2) a 3’ ligation moiety; wherein at least one of said first and said second ligation probes comprises an anchor sequence; b) ligating said first and said second ligation probes in the absence of a ligase enzyme to form a ligation product; c) capturing said ligation product on a substrate comprising a capture probe that hybridizes to said anchor sequence; and d) detecting the presence of said ligation product thereby detecting the presence of said target nucleic acid. Appeal Br. 44 (Claims App.) Appeal 2018-004820 Application 11/801,990 5 REJECTIONS2 A. Claims 51–60 are rejected under 35 U.S.C. § 112(a) or 35 U.S.C. § 112 (pre-AIA), first paragraph, as failing to comply with the written description requirement. Final Act. 8. B. Claims 51–60 are rejected under 35 U.S.C. § 112(a) or 35 U.S.C. § 112 (pre-AIA), first paragraph, as failing to comply with the enablement requirement. Final Act. 22. C. Claims 51–60 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 26–28,3 33–36, and 40 of co-pending Application No. 13/474,596.4 Final Act. 53. 2 The Examiner has withdrawn the following rejections: (1) the rejection of claims 51–60 as indefinite; (2) the rejection of claim 57 as being of improper dependent form; (3) the rejection of claims 51–60 as lacking utility; and (4) the rejection of claims 51–60 as being directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) to patent-eligible subject matter, without significantly more. Ans. 24. 3 On page 53 of the Final Action the Examiner states that the claims on appeal are rejected as being unpatentable over claims 26–18, 33–36, and 40 of Application No. 13/474,596. Final Act. 53. We understand this statement to contain a typographical error and that “claims 26–18” should be “claims 26–28” because, among other things, claim 18 in Application No. 13/474,596 had been cancelled. 4 Application No. 13/474,596 issued as Patent No. 10,066,257 on September 4, 2018. Thus, this double patenting rejection is no longer provisional. Claims 26–28, 33–36, and 40 of Application No. 13/474,596 appear to correspond, respectively, to claims 1, 2, 4, 6–9, and 13 of the ’257 patent. Appeal 2018-004820 Application 11/801,990 6 OPINION A. Written description rejection (claims 51–60) 1. Issue The Examiner concludes that the claims are directed to a “‘method for detecting the presence of a known target nucleic acid in a sample’ where the source, size and composition of the sample, as well as the form, length and source of the ‘target nucleic acid’ are without limit.” Final Act. 11. The Examiner concludes that, similarly, “[w]ith the exception that ligation is not to be achieved with a ligase, the means used to achieve ligation is unlimited.” Id. at 12. The Examiner concludes that the claims encompass “target nucleic acid[s] that will become ‘known’ years into the future.” Id.; see also id. at 18–19. The Examiner asserts that, accordingly, the claims encompass an enormous number of target genes. Id. at 14. The Examiner asserts that, [w]hile an applicant is not required to teach each and every possible embodiment encompassed by the claims, the specification still must provide a full, clear, and concise description of the genus encompassed by the claims so that one would be readily able to determine if a species fell within the claims’ scope, and to also reasonably suggest that applicant had possession of the invention at the time of filing. Final Act. 15. In contrast, the Examiner asserts, the Specification provides only eight artificial DNA sequences ranging in length from 12 to 29 nucleotides. Id. at 16. The Examiner further asserts that, while the Specification teaches that components useful in the claimed method, such as probes, “labels, primer sequences, promoter sequences, etc. are generally . . . known in the art,” Appeal 2018-004820 Application 11/801,990 7 “[o]bviousness . . . cannot be relied upon for satisfaction of the written description requirement.” Final Act. 16–17. Appellant contends that [t]he claimed methods utilize hybridization of ligation probes to hybridization domains in a primary target nucleic acid. Such hybridization is carried out using canonical base pairings that do not depend on the origin of DNA. As such, one of skill in the art would recognize that if the claimed methods can be used in conjunction with the exemplary target DNA provided in the specification, such methods can also be applied to DNA from other species. Further, one of skill in the art would recognize that the claimed methods can also be used in conjunction with target RNA sequences, as RNA follows canonical base pairing rules that are well known in the art. Accordingly, Appellant submits that one of skill in the art would recognize that Appellant was in possession of methods that can be utilized for the detection of target sequences of any target nucleic acid sequence based on the disclosure of the detection of the exemplary DNA sequences. Appeal Br. 16. 2. Analysis “[T]he test for sufficiency is whether the disclosure of the application relied upon reasonably conveys to those skilled in the art that the inventor had possession of the claimed subject matter as of the filing date.” Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1351 (Fed. Cir. 2010) (en banc) (citation omitted, alteration in original). We agree with Appellant that the Examiner has not established a prima facie case that the claims fail to comply with the written description requirement. The Examiner asserts that the disclosures do not sufficiently describe the genus of “target nucleic acid” recited in the claims, because the claims encompass an enormous number of target genes while the Specification Appeal 2018-004820 Application 11/801,990 8 provides only eight artificial DNA sequences ranging in length from 12 to 29 nucleotides. Final Act. 16. In particular, the Examiner notes that “the form, length and source of the ‘target nucleic acid’ are without limit” and the claims also encompass “target nucleic acid[s] that will become ‘known’ years into the future.” Final Act. 11–12. We are not persuaded. A “sufficient description of a genus . . . requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can ‘visualize or recognize’ the members of the genus.” Ariad, 598 F.3d at 1350. Furthermore, “[t]he descriptive text needed to meet [the written description requirement] varies with the nature and scope of the invention at issue, and with the scientific and technologic knowledge already in existence.” Capon v. Eshhar, 418 F.3d 1349, 1357 (Fed. Cir. 2005). In this case, Appellant’s claims are directed to a method for detecting known target nucleic acids in a sample, wherein two probes to distinct portions of the target hybridize to the target such that the probes are ligated in the absence of a ligase enzyme, and the ligation product is subsequently captured on a substrate by another probe, via an anchor sequence in the ligation product, and detected. Thus, a target nucleic acid may be any known nucleic acid of interest that will hybridize to probes – i.e., any known nucleic acid that follows the hybridization rules wherein the nucleotide adenine (A) is paired with the nucleotide thymine (T) and the nucleotide cytosine (C) is paired with the nucleotide guanine (G) or uracil (U), regardless of the actual nucleotide sequence of the target nucleic acid. Appeal 2018-004820 Application 11/801,990 9 Given the above, we agree with Appellant that the Examiner has not established a prima facie case that the disclosures do not adequately describe the genus of “target nucleic acids”: the exemplary target sequences disclosed in the Specification are “representative” of the genus vis-à-vis their method of hybridizing to the probes; likewise, the structural feature common to the members of the genus of target nucleic acids is simply the polynucleotide structure that allows for the specific and predictable hybridization of the nucleic acids to their complementary counterparts. More particularly, we agree that adequate written description does not require, as the Examiner appears to suggest, a listing of all possible target nucleic acid sequences. The Examiner has not suggested or cited persuasive evidence that different types or sequences of nucleic acids would follow different rules of hybridization. The Examiner next asserts that the disclosures do not sufficiently describe the “sample” from which presence of a known target nucleic acid may be detected, because “the source, size and composition of the sample . . . are without limit.” Final Act. 11. We are not persuaded for the same reasons discussed above. The Examiner has cited no persuasive evidence that target nucleic acids from different types of samples would behave different vis-à-vis their hybridization to the probes. The Examiner further asserts that the disclosures do not adequately describe the limitation of “ligat[ing a] first and [a] second ligation probes in the absence of a ligase enzyme,” because, “[w]ith the exception that ligation is not to be achieved with a ligase, the means used to achieve ligation is unlimited.” Final Act. 12. Appeal 2018-004820 Application 11/801,990 10 As an initial matter, we note that negative limitations, such as the limitation of “ligating . . . ligation probes in the absence of a ligase enzyme,” are not per se impermissible. Instead, the Federal Circuit has explained that “[n]egative claim limitations are adequately supported when the specification describes a reason to exclude the relevant limitation.” Santarus, Inc. v. Par Pharm., Inc., 694 F.3d 1344, 1351 (Fed. Cir. 2012). In this case, the Specification teaches that “non-enzymatic methods are available for detecting sequence variations” and that “[s]ome of the advantages of using non-enzymatic approaches for the nucleic acid target detection include lower sensitivity to non-natural DNA analog structures, ability to use RNA target sequences, lower cost and greater robustness under varied conditions.” Spec. ¶¶ 8, 12; see also id. ¶ 18 (stating that “the present invention provides methods and compositions for non-enzymatic chemical ligation reactions which greatly simplify the process of detecting and measuring nucleic acid targets”). Thus, we find that the claim limitation “ligating . . . in the absence of a ligase enzyme” is adequately supported by the Specification. To the extent the Examiner’s rejection is based on the finding that the Specification does not adequately describe the methods of ligation encompassed by the claims, we find that the Examiner has not established a prima facie case. In particular, the Specification explains with respect to the claimed invention that, “[i]n general, the probes comprise chemically reactive moieties (. . . ‘ligation moieties’) and bind to the target polynucleotide in a particular orientation, such that the chemically reactive moieties come into close spatial proximity, thus resulting in a spontaneous ligation reaction” (i.e., in the absence of a ligase enzyme). Spec. ¶ 59; see Appeal 2018-004820 Application 11/801,990 11 also Spec. ¶¶ 19, 35, 51, Fig. 1. The Specification also teaches that, while chemical ligation can spontaneously occur under the appropriate conditions, “‘activating’ agents or external stimuli can be used to promote the chemical ligation reaction.” Id. ¶ 66. Finally, the Specification provides examples of chemistries and ligation moieties useful for ligating the probes in the absence of a ligase enzyme, including halo leaving group chemistry, native peptide ligation, thioester ligation moieties, and nucleophile ligation moieties, as well as examples of activating agents. Id. ¶¶ 66, 68–97. While we appreciate the Examiner’s position that the limitation “ligating [a] first and [a] second ligation probes in the absence of a ligase enzyme” appears to encompass a wide variety of means of ligation, the Examiner provides no explanation why the above disclosures in the Specification do not adequately support the limitation at issue. The examiner “bears the initial burden . . . of presenting a prima facie case of unpatentability.” In re Oetiker, 977 F.2d 1443, 1445 (Fed. Cir. 1992). Our reviewing court has further explained that, [i]nsofar as the written description requirement is concerned, that burden is discharged by “presenting evidence or reasons why persons skilled in the art would not recognize in the disclosure a description of the invention defined by the claims.” . . . If . . . the specification contains a description of the claimed invention, albeit not in ipsis verbis (in the identical words), then the examiner . . . , in order to meet the burden of proof, must Appeal 2018-004820 Application 11/801,990 12 provide reasons why one of ordinary skill in the art would not consider the description sufficient. In re Alton, 76 F.3d 1168, 1175 (Fed. Cir. 1996). We find that the Examiner’s conclusory statements do not satisfy this burden.5 Finally, the Examiner asserts that the disclosures do not provide adequately written description support for components useful in the claimed method, such as labels, primer sequences, and promoter sequences, or methods of making the probes. Final Act. 16–17. In particular, the Examiner asserts that, while the Specification teaches that such components and methods are generally known in the art, “[o]bviousness . . . cannot be relied upon for satisfaction of the written description requirement.” We are not persuaded. As an initial matter, we note that the claims do not require primer or promoter sequences, although the Specification teaches that the ligation probes of the invention may include these sequences. More importantly, while we agree with the Examiner that “a description that merely renders the invention obvious does not satisfy the [written description] requirement,” Ariad, 598 F.3d at 1352, we once again note that “[t]he descriptive text needed to meet [the written description requirement] 5 In addition to the statement cited above (i.e., that “[w]ith the exception that ligation is not to be achieved with a ligase, the means used to achieve ligation is unlimited”), the Examiner’s only other analysis with respect to the written description rejection over this limitation states: With the disclosure teaching but four oligonucleotides that are admittedly an “Artificial Sequence,” such a limited showing does not reasonably suggest that applicant was in possession of the full genus of probes nor in possession of the full genus of means of ligating “probes in the absence of a ligase enzyme.” Final Act. 19–20. Appeal 2018-004820 Application 11/801,990 13 varies with the nature and scope of the invention at issue, and with the scientific and technologic knowledge already in existence.” Capon, 418 F.3d at 1357. Capon is illustrative in this regard. In that case, the Federal Circuit noted with respect to claims directed to chimeric DNA, that “[w]hen the prior art includes the nucleotide information [of the chimeric genes], precedent does not set a per se rule that the information must be determined afresh.” Capon, 418 F.3d at 1358. Instead, the court held that it was error to hold that “the specifications do not meet the written description requirement because they do not reiterate the structure or formula or chemical name for the nucleotide sequences of the claimed chimeric genes,” given that “the[] invention is not in discovering which DNA segments are related to the immune response, [which] is in the prior art, but in the novel combination of the DNA segments to achieve a novel result.” Id. Similarly, the invention in this case is not to a particular method of making individual probes, or to novel labels, primer sequences, or promoter sequences. Thus, we find that the Specification needs not reiterate, for instance, particular primer or promoter sequences in order to describe the invention. B. Enablement rejection (claims 51–60) 1. Issue The Examiner concludes that the Specification does not enable the full scope of the claims. In particular, the Examiner finds that the claims are extremely broad with respect to “the source, size and composition of the sample”; “the form, length and source of the ‘target nucleic acid’”; and the means to achieve ligation. Final Act. 23–28. The Examiner finds that “[t]he Appeal 2018-004820 Application 11/801,990 14 quantity of experimentation necessary [to practice the invention] is great, on the order of many man-years, and . . . with little if any reasonable expectation of successfully enabling the full scope of the claims,” because the Specification does not provide guidance for a skilled artisan to select the appropriate probe/primers for all the target nucleic acid encompassed by the claim. Id. at 28–32. Appellant contends that “the Examiner has mischaracterized the claimed method by focusing on the target nucleic acid sequences” because “the claims are not directed to determining new target sequences” but to “the detection of target sequences using novel methods.” Appeal Br. 21. Appellant contends that “[t]o suggest that a method of detecting nucleic acid relies on the knowledge of every potential target sequence, all of which will follow the same identical hybridization rules, is flawed.” Id. at 22; see also id. at 23. Appellant further contends that, “in light of the routine nature of the art involved in making and using the claimed method and the guidance provided by the present specification, the predictability of the art supports a finding of no undue experimentation.” Appeal Br. 23. 2. Analysis The Examiner bears the initial burden of showing that a claimed method is not enabled. See In re Wright, 999 F.2d 1557, 1561–62 (Fed. Cir. 1993) (“[T]he PTO bears an initial burden of setting forth a reasonable explanation as to why it believes that the scope of protection provided by that claim is not adequately enabled by the description of the invention provided in the specification of the application.”). In this case, we find that the Examiner has not established a prima facie case of lack of enablement. Appeal 2018-004820 Application 11/801,990 15 The Examiner’s rejection appears to be based on the fact that the claims encompass the detection of nucleic acids for which the nucleotide sequences, and therefore the sequences of suitable probes, have not yet been determined. Final Act. 23–32. The Examiner asserts that, therefore, practicing the full scope of the claimed method would require “determin[ing] the nucleotide sequence for each and every organism . . . in order to identify the correct nucleotide sequences for all probes and/or primers essential to the claimed invention.” Id. at 29. Because the Examiner finds that “[s]uch information is neither provided by the disclosure nor the art of record,” and because “nucleotide sequence for the genome of any given species” is highly unpredictable, the Examiner concludes that undue experimentation would be needed to practice the invention. Id. at 28– 32. We are not persuaded. The invention that must be enabled is the invention defined by the claims. Cf. CFMT, Inc. v. Yieldup Int’l Corp., 349 F.3d 1333, 1338 (Fed. Cir. 2003) (“Title 35 does not require that a patent disclosure enable one of ordinary skill in the art to make and use a perfected, commercially viable embodiment absent a claim limitation to that effect.”). Moreover, while a Specification must enable a skilled artisan to practice the full scope of the claimed subject matter, there is no requirement that the Specification discloses every species encompassed by the claims or exclude all inoperative embodiments. In re Vaeck, 947 F.2d 488, 496 (Fed. Cir. 1991) (explaining that “[i]t is well settled that patent applicants are not required to disclose every species encompassed by their claims, even in an unpredictable art”); Atlas Powder Co. v. E.I. du Pont De Nemours & Co., 750 F.2d 1569, 1576 (Fed. Cir. 1984) (holding that a claim does not lack Appeal 2018-004820 Application 11/801,990 16 enablement merely because it encompasses inoperative embodiments); In re Anderson, 471 F.2d 1237, 1242 (CCPA 1973) (“It is always possible to put something into a combination to render it inoperative. It is not the function of claims to exclude all such matters but to point out what the combination is.”). Instead, what is needed is sufficient disclosure, either through illustrative examples or terminology, to teach those of ordinary skill [in the art] how to make and how to use the invention as broadly as it is claimed. This means that the disclosure must adequately guide the art worker to determine, without undue experimentation, which species among all those encompassed by the claimed genus possess the disclosed utility. Vaeck, 947 F.2d at 496 (footnote omitted). In this case, the claims are not directed to identification of new or all possible target nucleic acids of interest. Rather, the claims are directed to a method for detecting known target nucleic acids in a sample, wherein two probes to distinct portions of the target hybridize to the target such that the probes are ligated in the absence of a ligase enzyme, and the ligation product is subsequently captured on a substrate by another probe, via an anchor sequence in the ligation product, and detected. Given that the claims are not directed to the identification of new or all possible target nucleic acids of interest, we do not agree with the Examiner’s apparent argument that achieving such a result is required for the claims on appeal to be enabled. Neither do we agree that claims must be drafted to exclude potential target nucleic acids that have not yet been sequenced. Appeal 2018-004820 Application 11/801,990 17 The Specification generally describes how to perform the claimed method, including by using conventional techniques such as hybridization, ligation, and detection of hybridization using a label. See, e.g., Spec. ¶¶ 34– 35, Figs. 1, 2A, 2B (schematic illustrations of target nucleic acid, ligation moieties, ligation probe, chemical ligation reaction, and anchor sequence.). The Specification also provides working examples of detecting target nucleic acids using ligation probes. See Spec. p. 37 (Examples), ¶ 33, Fig. 15. The Examiner has not provided persuasive evidence that a skilled artisan would have needed to experiment unduly to determine suitable probe and target sequences for practicing the invention as claimed, even if there exist potential target nucleic acids that have not yet been sequenced.6 6 To the extent the Examiner’s enablement rejection is based in part on the limitation relating to “ligating . . . in the absence of a ligase enzyme,” we remain unpersuaded for reasons similar to those discussed above with respect to the written description rejection. As to this limitation, the Examiner enablement rejection states only that, “[w]ith the exception that ligation is not to be achieved with ligase, the means used to achieve ligation is unlimited,” that “to enable the identification of useful probes with any and all possible ligation moieties attached thereto[] one would need to determine the nucleotide sequence of the various target sequences,” and that “the amount of time required . . . to identify all ligation moieties would require an unreasonable amount of routine experimentation.” Final Act. 23–24, 30. As discussed above, we do not agree that enabling disclosure for the claims on appeal requires determination of the nucleotide sequence of all possible target sequences. Likewise, the Examiner’s conclusory statements regarding breadth and the need for undue experimentation do not satisfy the Examiner’s initial burden in an enablement rejection to “set[] forth a reasonable explanation as to why . . . the scope of protection provided by [the] claim[s] is not adequately enabled by the description of the invention provided in the [S]pecification.” of the application.” See In re Wright, 999 F.2d 1557, 1561–62 (Fed. Cir. 1993) (emphasis added). Appeal 2018-004820 Application 11/801,990 18 Accordingly, we reverse the Examiner’s rejection of the claims as lacking in enablement. C. Double Patenting Rejection (claims 51–60) 1. Issue The Examiner concludes that, “[a]lthough the claims at issue are not identical [to claims 26–28, 33–36, and 40 of copending Application No. 13/474,596], they are not patentably distinct from each other because the claims for the ’596 application fairly teach a method of detecting a target nucleic acid that is present in a sample whereby one uses a first and second ligation probes.” Final Act. 53. Appellant contends that the obviousness-type double patenting rejection is improper “because the Examiner has simply made a conclusory statement that the pending claims are [not] patentably indistinct from the cited claims without providing a basis for the rejection.” Appeal Br. 40. In the Reply Brief, Appellant also contends that the present independent claims do not require a step of amplifying different ligation products as does independent claim 26 of the ’596 application (now claim 1 of the ’257 patent). Reply Br. 4. Appellant does not separately argue the claims. Thus, we limit our analysis to claim 51. The issue with respect to this rejection is whether a preponderance of the evidence of record supports the Examiner’s conclusion that claim 51 is not patentably distinct from claims 26–28, 33–36, and 40 of the ’596 application, now claims 1, 2, 4, 6–9, and 13 of the ’257 patent. Appeal 2018-004820 Application 11/801,990 19 2. Analysis To facilitate our analysis, we provide a side-by-side comparison of instant claim 51 and claim 1 of the ’257 patent below, with additional limitations in the reference claim not explicitly recited in instant claim 51 underlined for emphasis: Claim 51 Claim 1 of the ’257 patent 51. A method for detecting the presence of a known target nucleic acid in a sample comprising: 1. A method of detecting a plurality of different target nucleic acids in a target sample, a) providing a ligation substrate comprising: i) said known target nucleic acid comprising a first target domain and an adjacent second target domain, wherein the first target domain is upstream of the second target domain; wherein each target nucleic acid comprises an adjacent first and a second target domain, said method comprising: a) providing a reaction mixture comprising said target sample in lysis buffer comprising 2 to 6 molar guanidinium salt; b) contacting said reaction mixture with a plurality of different probes sets, each probe set comprising: ii) a first nucleic acid ligation probe comprising: i) a first nucleic acid ligation probe comprising: 1) a first probe domain 1) a first probe domain Appeal 2018-004820 Application 11/801,990 20 Claim 51 Claim 1 of the ’257 patent hybridized to said first target domain; and complementary to a first target domain of said one a target nucleic acid; 2) a first primer sequence; and 2) a 5’-ligation moiety; and 3) a 5’-ligation moiety; and iii) a second nucleic acid ligation probe comprising: ii) a second nucleic acid ligation probe comprising: 1) a second probe domain hybridized to said second target domain; 1) a second probe domain complementary to a second target domain of said one target nucleic acid; 2) a second primer sequence; and 2) a 3’ ligation moiety; 3) a 3’ ligation moiety; wherein at least one of said first and said second ligation probes comprises an anchor sequence; wherein one of said first or second nucleic acid ligation probes comprises a detectable label and the other comprises one of a binding partner pair; b) ligating said first and said second ligation probes in the absence of a ligase enzyme to form a ligation product; c) ligating said first and second ligation probes in the absence of a ligase enzyme to form a plurality of different ligation products; c) capturing said ligation product on a substrate comprising a capture probe that hybridizes to said anchor sequence; and d) contacting said ligation products with a solid support comprising the other of said binding partner pair such that Appeal 2018-004820 Application 11/801,990 21 Claim 51 Claim 1 of the ’257 patent said ligation products are captured on said solid support; e) washing said solid support; f) amplifying said different ligation products; and d) detecting the presence of said ligation product thereby detecting the presence of said target nucleic acid. g) detecting the presence of said ligation products. As shown in the comparison chart above, both instant claim 51 and claim 1 of the ’257 patent teach methods for detecting target nucleic acids in a sample. The ligation substrate of instant claim 51 is anticipated by and/or an obvious variant of the reaction mixture and probe sets of claim 1 of the ’257 patent: Both comprise (1) a target nucleic acid comprising first and second target domains; (2) a first and second nucleic acid ligation probe comprising (a) a probe domain complementary / hybridized to the target domains and (b) respectively, a 5’and a 3’-ligation moiety; (3) an “anchor sequence” or a “binding partner pair” used to capture the eventual ligation product to a substrate / solid support.7 7 While the reference claim does not explicitly recite that the first target domain is upstream of the second target domain, as does instant claim 51, the reference claim teaches that the first target domain is complementary to the ligation probe comprising the 5’-ligation moiety, suggesting that it is indeed upstream of the second target domain. Appeal 2018-004820 Application 11/801,990 22 The reference claim further teaches each of the steps of instant claim 51, including (1) providing a ligation substrate (i.e., contacting the reaction mixture above with probe sets); (2) ligating the first and second ligation probes in the absence of a ligase enzyme to form ligation product(s); (3) capturing ligation products on a substrate using anchor sequence / binding partner pair; and (4) detecting the presence of ligation product(s). Finally, although the reference claim does contain one or more limitations not explicitly recited in instant claim 51 – e.g., placing the target sample in lysis buffer comprising 2 to 6 molar guanidinium salt, including primer sequences in the ligation probes, washing the substrate / solid support, and amplifying ligation products – claim 51 does not preclude these additional steps and/or components because claim 51 uses the open transition phrase “comprising.” AFG Industries, Inc. v. Cardinal IG Co., 239 F.3d 1239, 1244–1245 (Fed. Cir. 2001) (explaining that comprising is an open transition phrase, the use of which indicates that the claim scope “may cover devices that employ additional, unrecited elements”). Accordingly, we agree with the Examiner that claim 51 is either anticipated by and/or not patentably distinct from one or more claims of the ’257 patent. In re May, 574 F.2d 1082, 1089 (CCPA 1978) (“[L]ack of novelty is the epitome of obviousness.”). Appellant contends that the Examiner has not provided a basis for an obviousness-type double patenting rejection. We are not persuaded. A rejection must be set forth in a sufficiently articulate and informative manner as to meet the notice requirement of 35 U.S.C. § 132, such as by identifying where or how each limitation of the rejected claims is met by the prior art Appeal 2018-004820 Application 11/801,990 23 references. In re Jung, 637 F.3d 1356, 1363 (Fed. Cir. 2011). We find the Examiner has done so. See, e.g., Final Act. 52–53; Ans. 32–34. Appellant contends in the Reply Brief that “present independent claims 51, 59 and 60 do not require a step of amplifying different ligation products as does independent claim 26 of the ’596 application [(now claim 1 of the ’257 patent)]” but “[t]he Examiner . . . has not addressed such difference or provide[d] reasons why a person of ordinary skill in the art would conclude that the invention defined in pending independent claims 51, 59, and 60 are anticipated by, or would have been an obvious variation of, the invention defined in a claim in the patent.” Reply Br. 4. We are not persuaded for the reasons already discussed above. Although claim 1 of the ’257 patent contains limitations, such as an amplification step, that does not appear in instant claim 51, it nevertheless anticipates claim 51 because claim 51 uses the transition phrase “comprising,” which encompasses the inclusion of additional, unrecited elements. Accordingly, we affirm the Examiner’s rejection of claim 51 on the ground of nonstatutory double patenting as being unpatentable over claims 26–28, 33–36, and 40 of co-pending Application No. 13/474,596, now claims 1, 2, 4, 6–9, and 13 of the ’257 patent. Claims 52–60, which are not separately argued, fall with claim 51. CONCLUSION In summary: Claims Rejected 35 U.S.C. § Reference(s)/Basis Affirmed Reversed 51–60 112(a) or 112 51–60 Appeal 2018-004820 Application 11/801,990 24 Claims Rejected 35 U.S.C. § Reference(s)/Basis Affirmed Reversed (pre-AIA), first paragraph 51–60 112(a) or 112 (pre-AIA), first paragraph 51–60 51–60 Obviousness-type Double Patenting: ’257 patent 51–60 Overall Outcome 51–60 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 Copy with citationCopy as parenthetical citation