DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. Applicant’s election without traverse of Group I and SEQ ID NO: 5 in the reply filed on June 29, 2026 is acknowledged.
Claims 1-8, 11-12, 16-17, 19, 22-24, and 53 are currently pending.
Claims 19 and 22-24 withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on June 29, 2026.
Claim 8 has been examined to the extent that the claim reads on the elected Cas protein (SEQ ID NO: 5). The additionally recited SEQ ID NOs: have been withdrawn from consideration as being directed to non-elected subject matter. Prior to allowance of the claim, any non-elected subject matter that is not rejoined with any allowed elected subject matter will be required to be removed from the claims.
Claim Rejections - 35 USC § 102
3. The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
4. Claims 1-7, 11-12, and 16-17 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Joung (medRxiv [Preprint]. 2020 May 8 found online at https://doi.org/10.1101/2020.05.04.20091231).
Regarding Claim 1 Joung teaches that they developed a test called STOP (SHERLOCK Testing in One Pot) for detecting SARS-CoV-2 in one hour that is suitable for point of care use (page 2). Joung teaches that STOPCovid test words in three steps: (1) lysis of virus containing patient sample, (2) detection of viral RNA using STOPCovid reaction (1 hour at 60ºC), and (3) visual readout (page 3). Joung teaches that during step 2, Sherlock master mix and a lysed sample are mixed thoroughly and incubated at 60ºC for 1 hour (page 10). The Sherlock master mix comprises a Cas protein with collateral cleavage activity (AapCas12b) and a guide RNA (AapCas12b crRNA). Joung teaches that AacCas12b is thermostable and maintains sufficient activity in the temperature range of LAMP (55-65ºC) (page 4, Fig 2B, and Fig 4C).
Regarding Claim 2 Joung further teaches that that the STOPCovid detection system using reporter DNA for fluorescent readout (pages 7, and 9-11).
Regarding Claim 3 Joung teaches performing incubation at 60ºC for 1 hour (page 10).
Regarding Claim 4 Joung teaches that the STOPCovid test combines LAMP amplification with a Sherlock reaction (page 5).
Regarding Claim 5 Joung teaches that the Sherlock master mix comprises Bst 2.0 WarmStart DNA polymerase (pages 7-8). This polymerase is being interpreted as a thermostable polymerase.
Regarding Claim 6 Joung teaches that the steps of amplifying and contacting are performed in a single vessel (page 2, Fig 1A).
Regarding Claim 7 Joung teaches AapCas12b which is a Cas12 protein (page 7).
Regarding Claims 11-17 Joung teaches performing a detection assay (STOPCovid) utilizing a Cas protein (AapCas12b) with collateral cleavage activity. Joung teaches that this Cas protein is thermostable and maintains sufficient activity in the temperature range of LAMP (55-65ºC) (page 4, Fig 2B, and Fig 4C).
Claim Rejections - 35 USC § 103
5. The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
6. Claim 8 is rejected under 35 U.S.C. 103 as being unpatentable over Joung (medRxiv [Preprint]. 2020 May 8 found online at https://doi.org/10.1101/2020.05.04.20091231) in view of Zhang (US 2021/0292823 Pub 9/23/2021 and Filed 6/5/2020).
The teachings of Joung are presented above.
Joung does not teach a method wherein the Cas protein has an amino acid sequence that is at least 80% identical to that of SEQ ID NO: 5.
However Zhang discloses SEQ ID NO: 61931. Zhang teaches that this is a thermostable Cas12 protein. It is noted that this sequence is 100% identical to that of SEQ ID NO:5 (paras 0125, 0127).
Accordingly, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Joung by using a Cas protein having the sequence of SEQ ID NO: 5 as suggested by Zhang. In the instant case Zhang discloses SEQ ID NO: 61931 which is 100% identical to SEQ ID NO: 5 and is considered to be a thermostable Cas protein. The claim would have been obvious because the substitution of one known thermostable Cas12 protein for another would have yielded predictable results to one of ordinary skill in the art at the time of the invention.
7. Claim 53 is rejected under 35 U.S.C. 103 as being unpatentable over Mason (US 2022/0133850 with priority to PCT/US2020/016163 Filed Jan 31, 2020) in view of Joung (medRxiv [Preprint]. 2020 May 8 found online at https://doi.org/10.1101/2020.05.04.20091231).
Regarding Claim 53 Mason teaches a method wherein cells are treated to disrupt endogenous TREM2. Mason teaches that an exemplary method of disrupting endogenous TREM2 in cells is using a CRISPR/Cas system (e.g., CRISPR/Cas9 or CRISPR/Cas12a) with a TREM2-specific guide RNA (gRNA) to induce one or more double-strand breaks (DSB) (para 0365). Thus Mason teaches a method of cleaving at least one target nucleic acid (TREM2) in a cell comprising contacting a cell with a Cas protein with collateral cleavage activity (Cas12a) and at least one guide capable of hybridizing to the at least one target nucleic acid, wherein the Cas protein is capable of forming a complex with the at least one guide and causing a break in the at least one target nucleic acid.
Mason does not teach that the Cas enzyme is thermostable at temperatures above at least 56°C.
However Joung teaches that AacCas12b is thermostable and maintains sufficient activity in the temperature range of LAMP (55-65ºC) (page 4, Fig 2B, and Fig 4C).
Accordingly, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Mason by using a Cas enzyme, such as AacCas12b, that is thermostable at temperatures above 56ºC as suggested by Joung. One of skill in the art would have been motivated to use a thermostable Cas for the benefit of being able to retain cleavage activity at high temperatures.
Double Patenting
8. The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
9. Claims 1-8, 11-12, and 16-17 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of copending Application No. 19/080,542 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other. Both sets of claims are drawn to a detection method comprising steps of: contacting a CRISPR-Cas complex comprising: a Cas protein with collateral cleavage activity that is thermostable; and a guide RNA selected or engineered to be complementary to a target nucleic acid sequence; with a sample potentially comprising a target nucleic acid sequence (see clm 1 of the copending application). The instant claims state that the Cas enzyme is thermostable above at least 56ºC, whereas the copending claims state that the Cas enzyme is thermostable above about 55ºC. Both sets of claims encompass Cas enzymes that are thermostable greater than 56ºC. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
10. Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMANDA HANEY whose telephone number is (571)272-8668. The examiner can normally be reached Monday-Friday, 8:15am-4:45pm EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Wu-Cheng Shen can be reached at 571-272-3157. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/AMANDA HANEY/Primary Examiner, Art Unit 1682
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