Microsoft Technology Licensing, LLCDownload PDFPatent Trials and Appeals BoardJul 26, 20212020005457 (P.T.A.B. Jul. 26, 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. 15/626,021 06/16/2017 Kris K. Ganjam MS2-0133US 7725 142810 7590 07/26/2021 Newport IP, LLC 1400 112th Ave SE Suite 100 Bellevue, WA 98004 EXAMINER LEITH, NANCY J ART UNIT PAPER NUMBER 1636 NOTIFICATION DATE DELIVERY MODE 07/26/2021 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): docketing@newportip.com eofficeaction@appcoll.com scott@newportip.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte KRIS K. GANJAM Appeal 2020-005457 Application 15/626,021 Technology Center 1600 Before ERIC B. GRIMES, JEFFREY N. FREDMAN, 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 as obvious claims to a homology directed repair system that adds a barcode that uniquely identifies a gene. 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(a). Appellant identifies the real party in interest as Microsoft Technology Licensing, LLC. (Appeal Br. 3.) Appeal 2020-005457 Application 15/626,021 2 STATEMENT OF THE CASE Homologous directed repair (HDR) is a mechanism that cells use to repair double stranded breaks (DSB) in a strand of deoxyribonucleic acid (DNA). (Spec. ¶ 29.) Appellant’s claim is directed to a system for use in HDR. Claims 9–20 are before us on appeal. Claim 16, reproduced below, is illustrative of the claimed subject matter: 16. A system comprising: a gene, that when expressed, produces a homology direct repair (HDR) template; a double stranded polynucleotide including a target site, wherein the target site is not in the gene; the HDR template including a first sequence complementary to a first subsequence of the target site, a second sequence complementary to a second subsequence of the target site, and a barcode region having a sequence of nucleotides that uniquely identifies the gene; and an enzyme configured to create a double strand break in the double stranded polynucleotide at the target site; wherein the HDR template is configured to add the barcode region into the double stranded polynucleotide by HDR to produce a modified double stranded polynucleotide. (Appeal Br. 27.) Appeal 2020-005457 Application 15/626,021 3 The prior art relied upon by the Examiner is: Name Reference Date Gill et al. US 2017/0369870 A1 Dec. 28, 2017 Holmes et al. US 9,957,526 B2 May 1, 2018 Dominik Paquet et al. Efficient introduction of specific homozygous and heterozygous mutations using CRISPR/Cas9, 533 Nature, 125–129 2016 The following grounds of rejection by the Examiner are before us on review: Claims 9–11 and 14–20 under 35 U.S.C. § 103 as unpatentable over Paquet and Gill.2 Claims 12 and 13 under 35 U.S.C. § 103 as unpatentable over Paquet, Gill, and Holmes. DISCUSSION Claim 16: Obviousness over Paquet and Gill Appellant focuses its arguments with respect to this rejection on claim 16. (See Appeal Br. 12, 16–17; Reply Br. 5, 7, 9–11.) We, thus, focus on the rejection as it relates to claim 16. The Examiner found that Paquet discloses a homology directed repair system that includes (1) a double stranded polynucleotide gene that has a target site, (2) “an enzyme (CRISPR/Cas9) that will create a double stranded 2 The Examiner relies on the priority claim to US Provisional Application 62/354,516, filed June 24, 2016 (Gill ’516). (Ans. 4.) The Examiner states that “the ’516 provisional application does provide full support for the disclosure of the ’870 application, as applied in the rejections.” (Id. at 8.) Appeal 2020-005457 Application 15/626,021 4 break in the target site,” and (3) an HDR template that has a barcode sequence, where the HDR template could be either single stranded or double stranded. (Ans. 4 (citing Paquet, Abstr., and Figs. 1 and 3); Id. at 9.) The Examiner found that Paquet does not disclose that the target sequence is not located in the gene, as required by claim 16. (Id. at 4.) The Examiner found that Gill also discloses HDR systems using a CRISPR enzyme system. (Id. (citing Gill ¶¶ 55–93; Gill ’516 ¶¶ 80–91).) The Examiner further found that Gill teaches “the target can be a genomic locus, a genomic sequence or an extrachromosomal locus.” (Id. (citing Gill ¶ 162; Gill ’516 ¶¶ 47, 113).) The Examiner also found that Gill teaches that the target sequence can be any nucleic acid including a gene, as well as a non-coding nucleic acid sequence. (Id. at 4–5 (citing Gill ¶¶ 118, 169; Gill ’516 ¶¶ 112–113).) Additionally, the Examiner found that Gill discloses that the “editing cassette . . . can introduce mutations into a target sequence, which can be assayed for by measuring gene activity.” (Id. at 5 (citing Gill ¶¶ 206, 217).) The Examiner indicates that “Gill provides for identification of genes and multiplex identification of genes via a barcode, which may be outside of a target site” and that “the system can also provide for measurement and detection of gene expression and/or alteration of gene expression activity.” (Id. at 9.) The Examiner determined that it would have been obvious “that the system disclosed and suggested by Paquet and Gill can be used to target any specific desired nucleic acid sequence, including a non-coding, non-gene sequence because the guide sequences can be created to target any desired sequence, whether within or not in a gene.” (Id. at 5.) The Examiner further determined that “[o]ne of ordinary skill in the art would have a predictable Appeal 2020-005457 Application 15/626,021 5 and reasonable expectation of success in designing the system to target any sequence in any genome or cell.” (Id.) The Examiner noted that “Gill is deemed to provide motivation to combine the references” and that “[o]ne of ordinary skill in the art, desiring to track edits and repair of genetic material would turn to both Paquet and Gill.” (Id. at 9.) We agree with the Examiner’s conclusion of obviousness of claim 16. A. Application of Gill as prior art Appellant does not dispute that Gill ’516 has a filing date that precedes the filing date of Appellant’s application. (See Appeal Br. 10.) However, Appellant argues with respect to Gill that the provisional filing and the utility filing “are clearly different” and “[t]he burden is on the Office to support rejections” but “[t]he Office has not shown that all of the passages of the Gill ’870 application relied upon to support the grounds of rejection are entitled to a priority date earlier than Appellant’s claim.” (Reply Br. 5– 6.) Appellant notes that there may be support, or not but “[t]here is nothing in the record to support a determination either way” and that “any grounds of rejection which rely on citations to the Gill ‘870 application fail to establish a prima facie case of obviousness.” (Id. at 6.) Appellant argues that the rejection does in fact rely on “some features” of Gill for which there are no citations to any corresponding portion of Gill ’516. (Id.) Appellant asserts that “such features are not shown in the record to have a priority date prior to that of Appellant’s claims” and that “the Board should base its analysis of the sufficiency of the ground of rejection only on citations to the Gill ‘516 provisional.” (Id.) Appeal 2020-005457 Application 15/626,021 6 We find that the Examiner’s rejection does cite to one feature of Gill without pointing out where in Gill ’516 there is support; namely, that the target sequence that was edited by the editing cassette “can be assayed for by measuring gene activity.” (Ans. 5 (citing Gill ¶¶ 206, 217).) However, we conclude that this feature is not relevant to any of the system claims on appeal as it represents an intended use recitation that can be satisfied by finding no gene activity or some gene activity. A “mere statement of a new use for an otherwise old or obvious [product] cannot render a claim to the [product] patentable.” In re Zierden, 411 F.2d 1325, 1328 (CCPA 1969). And, in any event, we note that Gill ’516 paragraph 144 has a similar disclosure to Gill paragraph 217 stating that “[i]n addition or as an alternative to activity screens, more general properties . . . can be efficiently tested using methods . . . disclosed herein.” And Gill ’516, like Gill, further explains that “barcoding technology” can be used to map residue changes. (Gill ’516 ¶¶ 145–146; see also Gill ¶¶ 218–219.) Consequently, we conclude that the Examiner’s reliance on Gill as prior art is supported. In any event, we base our analysis of the Examiner’s rejection with respect to Gill on the disclosure provided in Gill ’516. B. The claimed barcode requirement Appellant, although conceding that the term barcode is used throughout Gill ’516, argues that the Examiner does not cite to any passages of Gill ’516 concerning barcodes and thus, “the record does not show how the Office is interpreting the ‘barcode’ of Gill or which specific aspects of the barcode allegedly teach or suggest features of Appellant’s claims.” (Reply Br. 7.) We do not find this argument persuasive of non-obviousness. Appeal 2020-005457 Application 15/626,021 7 Appellant’s independent claim 16 requires a gene encoding a first HDR template where the template includes a barcode sequence that uniquely identifies the gene. Appellant’s Specification does not define the term barcode. It simply indicates that the barcode sequence “can include any number of nucleotides that allow for identification of the gene.” (See Spec. ¶ 139.) The Examiner cites to paragraphs 80–91 of Gill ’516, which teach that CRISPR Enabled Trackable genome Engineering (CREATE) methods employ a CREATE recorder system that includes a trackable sequence (Gill ’516 ¶ 81), such as a barcoding sequence that can be a unique DNA sequence (Gill ’516 ¶ 87; see also id. ¶ 183). We conclude that such disclosure sufficiently establishes that the barcode of Gill ’516 is one that uniquely identifies a gene encoding the HDR template, and thus meets the requirement of “barcode” recited by claim 16. C. A gene that when expressed produces an HDR template that includes the barcode Appellant argues that the Examiner’s rejection is in error because, although the references show some of the tools used in the claimed system, the references do not teach or suggest, alone or in combination, a system that includes a gene that when expressed produces the HDR template that includes a barcode region and wherein the HDR template is configured to add the barcode region into the double stranded polynucleotide by HDR. (Appeal Br. 16–17.) We do not agree with Appellant’s assessment. We find Gill ’516 teaches or suggests the foregoing. As discussed above, the Examiner pointed to Gill ’516 paragraphs that teach a barcode as claimed. Gill ’516, in paragraphs cited by the Examiner, also teaches that the system includes a cassette that couples two elements, guide nucleic acids (a gRNA encoding gene) designed for targeting a user specific site in the Appeal 2020-005457 Application 15/626,021 8 genome as well as a homology arm that includes a trackable sequence “designed to undergo homologous recombination with the chromosome at the site of nucleic acid-guided nuclease-mediated double strand break,” i.e., “the recording sequence is incorporated by homologous recombination or homology-driven repair systems.” (Gill ’516 ¶¶ 81, 85, 87, 88, 90.) In short, we conclude that the Examiner has provided sufficient evidence that Gill ’516 discloses or at least suggests that the unique DNA tracking sequence of the HDR template will be added into the double stranded polynucleotide by HDR. D. Reason to Combine Appellant also argues that the Examiner’s rejection is in error because the asserted reason to combine Paquet and Gill is merely a conclusory statement with no supporting underlying rationale. (Appeal Br. 20–21; see also Reply Br. 5 (“Because the language of the [new grounds of] rejection [in the Answer] is essential identically [sic], Appellant reiterates all previous arguments made in the Appeal Brief without repeating those arguments here.”).) Appellant contends that “[t]he ability of one to freely select targets for HDR directed insertion is not unique to any of the three references” but simply a “characteristic of this well-established molecular biology tool” and as such is not a “rationale for combining the references.” (Id.) Appellant indicates that the Examiner does not “provide[] a clear articulation of why a person having ordinary skill in the art would be motivated to combine the cited references.” (Reply Br. 10.) We do not find the foregoing argument persuasive of error. First, for the reasons discussed above, we conclude that Gill ’516 suggests the claimed invention. In affirming a multiple reference rejection Appeal 2020-005457 Application 15/626,021 9 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). Second, even considering Paquet with Gill, we note “[t]he combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results.” KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007). As Appellant recognizes, both Paquet and Gill describe HDR, which is a “well-established molecular biology tool” that is “flexible and versatile.” (Appeal Br. 20–21.) Gill ’516 teaches, as the Examiner found, that the target site to which HDR can be directed can be in a gene or not in the gene (Gill ’516 ¶¶ 47, 113) and that the editing cassette can introduce DNA changes into that target site which cassette includes a barcode to track the edit, see citations to Gill ’516 supra. We conclude that the cited prior art supports a conclusion that the claimed invention is merely the combination of known elements yielding a predictable result, i.e., a system with the claimed components in which the gene would be capable of being expressed to produce the HDR template, as evidenced by Paquet, and where the HDR template taught by Gill ’516 would reasonably be predicted to add the barcode into a double stranded polynucleotide by HDR. For the foregoing reasons, we affirm the Examiner’s rejection of claim 16 as being obvious from the teachings of Paquet and Gill as supported by Gill’s priority application Gill ’516. Claims 9–11, 14, 15, and 17–20 have not been argued separately and therefore fall with claim 16. 37 C.F.R. § 41.37(c)(1)(iv). Appeal 2020-005457 Application 15/626,021 10 Claim 13: Obviousness over Paquet, Gill, and Holmes Claim 13 depends from claim 9, an independent claim with very similar claim elements to claim 16.3 Claim 13, however, requires the gene to include certain additional specific regions. Appellant argues that the Examiner’s rejection of claim 13 is in error because the rejection (1) “does not provide any evidence” that “a first splicing region” is “taught or suggested by the prior art,” (2) “does not identify any teaching or suggestion of ‘a 3’ untranslated region (UTR) and a 5’ UTR’ in a prior art reference,” and (3) “does not identify any teaching or suggestion of a ‘coding region that includes an intron and an exon’ in a prior art reference.” (Appeal Br. 18.) In addition, Appellant argues that the rejection also “does not identify these features in combination as an RNA precursor encoded by a gene.” (Id.) We agree with Appellant that the Examiner has failed to establish a prima facie case that claim 13 is obvious from the teachings of Paquet, Gill, and Holmes. Gill ’516 describes the CRISPR system as including a gene sequence that is expressed as a guideRNA that targets particular sites because it is complementary to a region of the target site. (See, e.g., Gill ’516 ¶ 47, 64; see also Paquet, Fig. 1.) Such guideRNA is known to be expressed from a sequence homologous to the target gene sequence in a CRISPR system as precursor RNA which is further processed to result in the guideRNA. Thus, Gill ’516 teaches or suggests the HDR template includes 3 Appellant does not separately argue the rejection of claim 12. “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.” Hyatt v. Dudas, 551 F.3d 1307, 1314 (Fed. Cir. 2008). Appeal 2020-005457 Application 15/626,021 11 a sequence that when expressed encodes an RNA precursor homologous to the target gene that includes a single stranded polynucleotide. Additionally, as the Examiner’s rejection states, Gill teaches the target for cassette sequences that are trackable can be inserted in an untranslated region or a gene and that the cassettes can target multiple sequences. (See Gill ’516 ¶¶ 84, 87, 112–113; see also Ans. 4–5.) Moreover, Gill ’516 explains that the barcode can be located “outside of the open reading frame of the gene.” (Gill ’516 ¶ 136; see also Gill ¶ 118.) Given the foregoing teachings, we understand Gill ’516 to teach or suggest that the gene encoding the HDR template would include a sequence that corresponds to the barcode sequence and sequences to direct the inclusion of the barcode to a region outside of an open reading frame such as into untranslated regions. Holmes further supports the obviousness of including sequences in HDR templates that are for non-coding regions. (See, e.g., Holmes 4:38–40.) The Examiner relied on Holmes for teaching the inclusion of splice acceptor sequences in the HDR template for targeted insertion. (Ans. 6 (citing Holmes 28:8–19).) We conclude that in light of the specific teachings of Holmes, including specific splice acceptor sequences that may be used, one of ordinary skill in the art would have found it obvious to include such a sequence in the HDR templates of Gill and Paquet for its known advantages. On the other hand, the Examiner has not identified where the cited prior art teaches or suggests inclusion in the sequence of the gene encoding a first HDR template “a 3’ untranslated region (UTR) and a 5’ UTR,” and a “coding region that includes an intron and an exon” as recited in claim 13. Instead, the Examiner simply asserts that “one of ordinary skill in the art Appeal 2020-005457 Application 15/626,021 12 would have understood that expression of a gene would inherently progress from an RNA precursor to an expressed protein, and that the recited components are present in the constructs disclosed and suggested by Paquet, Gill, and Holmes.” (Ans. 10.) The Examiner, however, does not establish that fact and does not indicate that the recited 3’ and 5’ UTR regions, and that an intron as well as an exon coding region are required and thus necessarily present in an HDR template gene construct. Thus, we reverse the Examiner’s rejection of claim 13 as being obvious from the teachings of Paquet, Gill, and Holmes. DECISION SUMMARY In summary: Claim(s) Rejected 35 U.S.C. § Reference(s)/Basis Affirmed Reversed 9–11, 14–20 103 Paquet, Gill 9–11, 14–20 12, 13 103 Paquet, Gill, Holmes 12 13 Overall Outcome 9–12, 14–20 13 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