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 .
Election/Restrictions
Applicant’s election without traverse of group I, CRISPR chain reaction system, and species nucleotide sequence configured to bind secondary crRNA, ssDNA, and Cas12a in the reply filed on 09/29/2025 is acknowledged.
Claims 10, 24-27 and 31-32 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 09/29/2025.
Claims 1-6, 8-9, 16, 19-20, 23, and 30 are under examination.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-6, 8-9, 16, 19-20, and 23 rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 recites a CRISPR chain reaction system for amplifying the detection sensitivity of a primary CRISPR-based target detection system…wherein the CCR system amplifies the detection sensitivity compared to the CRISPR-based target detection system alone. The recitation of amplifying the detection sensitivity and amplifies the detection sensitivity in the preamble and wherein clauses renders the claim indefinite. It is unclear what structural features of the claimed system is required for amplifying the detection sensitivity of a primary CRISPR-based target detection system. Amplifying comprises creating copies of specific DNA or RNA sequences. The claimed system does not require any amplification structures or features. Alternatively amplifying the detection sensitivity could encompass making the system more responsive to small changes, however there are no structural features claimed that would render this result. It is unclear if the recitation of amplifying is with respect to generating nucleic acid sequences or if it is with respect to increasing sensitivity of detection. Even if the claim clearly indicated amplifying is with respect to either interpretations, it is unclear what structural features would be required to attain the claimed features. Because the preamble and wherein clause render the claim indefinite, one of skill in the art would not be apprised of infringing on the claimed system. This rejection may be overcome by deletion of the phrases “for amplifying the detection sensitivity of a primary CRISPR-based target detection system” and “wherein the CCR system amplifies the detection sensitivity compared to the CRISPR-based target detection (CBTD) system alone”.
Claim 20 recites “a commercially available CBTD system”. This limitation is similar to reciting a trademark in a claim. The limitation is used to identify or describe a particular material or product and the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the recitation of a commercially available CBTD system cannot be used properly to identify any particular material or product. A commercially available CRISPR based target detection system does not identify or describe the goods associated the system. Which of the CBTD are commercially available? Commercially available products may change over time and therefore the claim is defined. For example, the CBTD that is commercially available today may not be commercially available after a given time period. Additionally it is unclear what the CRISPR based target detection system is “based” on. Does this require only reagents, some elements and is this a system for target detection using CRISPR or one of its reagents used in the system?. In the present case, the recitation of commercially available CBTD is indefinite and, accordingly, the identification/description is indefinite.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-6, 8-9, 16, 19-20, 23, and 30 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Jain et al. (US20220380835A1 or WO2021/092519 A1 (which is the PCT/US2020/059577 of PgPub), cited by PgPub).
The applied reference has a common inventor with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2). This rejection under 35 U.S.C. 102(a)(2) might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C. 102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B) if the same invention is not being claimed; or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed in the reference and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement.
With regard to claim 1, Jain teaches CRISPR detection system comprising a modified crRNA, Cas enzyme with trans cleavage activity a crRNA that includes the guide sequence and a polynucleotide extension sequence that includes ssDNA and a probe that includes an oligonucleotide element labeled with a detectable labeled (see para 79).
With regard to claim 2-6 and 30, Jain teaches at least two different crRNA with polynucleotide extension sequences (see para 93 and 97) (plurality of secondary crRNAs capable of forming a complex with Cas enzyme) (claim 30). Jain teaches an extension sequence, a linker and a complementary sequence that is complementary to extension and guide RNA (plurality of activators, guide RNA). Jain teaches the extension sequence, linked and complementary sequence form a toehold conformation, which unfolds when guide sequence bind the target polynucleotide (see para 98) (blocking moieties bound to secondary crRNA and activator, guide RNA). The toehold conformation comprises a nucleotide sequence configured to bind the crRNA and guide RNA, prevents binding of crRNA to guide RNA (see para 98-99) (claim 2-4 and 5-6).
With regard to claim 8-9, Jain teaches the CRISPR associated enzyme is Cas12a (see para 90).
With regard to claim 16, Jain teaches the blocking nucleotide sequence, toehold linker sequence linked to the 3’ sequence and the guide RNA and forms a hairpin conformation (see para 99, 218 and fig 36A-B) (claim 16).
With regard to claim 19-20 and 23, Jain teaches a kit comprising detection system and test strips (See para 125). Jain teaches commercially available test strips (see para 134). Thus, Jain teaches a kit comprising CRISPR detection system comprising a modified crRNA, Cas enzyme with trans cleavage activity a crRNA that includes the guide sequence and a polynucleotide extension sequence that includes ssDNA and a probe that includes an oligonucleotide element labeled with a detectable labeled which encompasses the claimed CCR system and primary CBTD system. Jain further teaches the kit comprises commercially available CRISPR based detection system (CBTD) which includes commercial test strips. Jain teaches excess concentration of Cas, crRNA and guide RNA (See para 164).
Claims 1-6, 8-9, 16, 19-20, 23 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Nguyen (BioRxiv, cited on IDS).
With regard to claim 1, Nguyen teaches CRISPR detection system comprising a modified crRNA, Cas enzyme, with trans cleavage activity a crRNA that includes the guide sequence and a polynucleotide extension sequence that includes ssDNA and a probe that includes an oligonucleotide element labeled with a detectable labeled (see page 2 and fig 1).
With regard to claim 2-6, Nguyen teaches an extension sequence, a linker and a complementary sequence that is complementary to extension and guide RNA (plurality of activators, guide RNA) (see fig 1 and fig 2) Nguyen teaches the extension sequence, linked and complementary sequence form a toehold conformation, which unfolds when guide sequence bind the target polynucleotide (blocking moieties bound to secondary crRNA and activator, guide RNA) (see fig 2) The toehold conformation comprises a nucleotide sequence configured to bind the crRNA and guide RNA, prevents binding of crRNA to guide RNA (see fig 2) (claim 2-4 and 5-6).
With regard to claim 8-9, Nguyen teaches the CRISPR associated enzyme is Cas12a (see para 90).
With regard to claim 16, Nguyen teaches the blocking nucleotide sequence, toehold linker sequence linked to the 3’ sequence and the guide RNA and forms a hairpin conformation (see fig 1-2) (claim 16).
With regard to claim 19-20 and 23, Nguyen teaches a kit comprising detection system and test strips (See pg 3 and methods). Nguyen teaches commercially available test strips (see fig 3). Thus, Nguyen teaches a kit comprising CRISPR detection system comprising a modified crRNA, Cas enzyme with trans cleavage activity a crRNA that includes the guide sequence and a polynucleotide extension sequence that includes ssDNA and a probe that includes an oligonucleotide element labeled with a detectable labeled which encompasses the claimed CCR system and primary CBTD system. Nguyen further teaches the kit comprises commercially available CRISPR based detection system (CBTD) which includes commercial test strips. Nguyen teaches excess concentration of Cas, crRNA and guide RNA (See methods).
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-6, 8-9, 16, 19-20, 23, and 30 is/are rejected under 35 U.S.C. 103 as being unpatentable over Doudna (US 10253365B1) in view of Garcia-Guerra (WO2020/044039 A1, cited on IDS).
Doudna teaches a CRISPR system that comprises a guide RNA, Cas12a, and detector probes. Doudna teaches guide RNA that binds to type V CRISPR Cas effector protein, Cas12a, (see column 35, lines 65-67 and column 36, lines 1-3) (claim 8-9, Cas12a) Doudna teaches hybrid RNA/DNA can be made and guide RNA includes guide sequence and a constant region which binds Cas12a. Doudna teaches the constant region can be extended (see column 37, lines 18-24) (plurality of crRNA capable of forming secondary crRNA/Cas complex). Doudna does not teach single molecules and as such the teachings of Doudna will encompass a plurality of each component of the claimed system. It is noted the claims do not require different components only a plurality of each which encompasses more than one but can have the same sequence. Doudna further teaches two or more guide RNAs (see column 37, lines 30-43) and different targets (see column 37, lines 47-55)(plurality of secondary activators capable of forming complex with Cas enzymes). Doudna teaches the guide RNA can comprise modifications (see column 38, lines 26-32). Doudna teaches a labeled detector dsDNA that comprises one or more modifications. Doudna teaches the target is ssDNA or dsDNA (see column 15, lines 7-10) (claim 6)
With regard to claim 19-20, Doudna teaches a kit that comprises two or more guide RNA (See column 38, lines 1-4). Doudna teaches a kit comprising a labeled detector dsDNA, guide RNA, precursor guide RNA array comprising two or more guide RNA, and Cas12a (see column , lines 53-63). Doudna teaches the kit comprises labeled detector ssDNA with fluorescein emitting dye pair (commercially available component of the system) (see column 46, lines 53-64). With regard to claim 30, Doudna teaches multiple Cas proteins (see column 46 lines 51-53), two or more guide RNA that bind to different target guide RNAs (see column 38, lines 5-25 and column 46 lines 53-64).
Doudna does not teach plurality of blocking moieties bound to secondary crRNA. Doudna does not teach blocking nucleotide sequence connected to secondary crRNA forming a hairpin conformation.
Garcia Guerra teaches modified sgRNAs, use of gates for binding and activating nucleic acid binding of CRISPR enzyme (see pg. 32). Garcia Guerra teaches a bulge and stem loops for the blocking domain (see fig 5B and 10A) and teaches a crRNA linked to a tracrRNA and a blocker domain. Garcia Guerra teaches the nucleotide sequence of the Blocker domain is partially complementary to the nucleotide sequence of crRNA (see pg 13 and pg 16). Garcia Guerra teaches flanking on both sides of guide RNA by toeholds (see pg. 53).
One of ordinary skill in the art would have been motivated to use toehold conformation and blocking sequences as taught by Garcia Guerra with the system as taught by Doudna because Doudna teaches the use of guide RNA with extensions and spacers to allow for detection of target nucleic acid and Garcia Guerra teaches guide RNAs and the advantage of using flanking toehold sequence to tailor and initiate activity to increase specific and efficiency. One of ordinary skill in the art would have had a reasonable expectation of success for using toehold conformation sequences as taught by Garcia Guerra with the system as taught by Doudna because the underlying material, guide RNA taught by Garcia Guerra and Douda and the systems along with components are known, successfully demonstrated and commonly used.
Double Patenting
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.
Claims 1-6, 16, 19-20, 23 and 30 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-12, 17-18 of copending Application No.17775206.
This is a provisional nonstatutory double patenting rejection.
Although the conflicting claims are not identical, they are not patentably distinct from each other because claims 1-6, 8-9, 16, 19-20, 23 and 23 would have been anticipated by claims 1-4, 11, and 17-18 of ‘206. Specifically claim 1-9 of’206 requires a system comprising a Cas enzyme, crRNA with an extension sequence and comprises a guide RNA and plurality of probes with a detectable label. This claim anticipates claim 1 of the instant application because the extension sequence of claim 1-9 of ‘206 encompasses a blocker sequence of the instant claims. Additionally dependent claim 17-18 comprises a toehold conformation on the crRNA that is a blocking sequence and forms a hairpin structure which is identical in scope and encompasses instant claims 2-6 and 16. Claim 10 of ‘206 encompasses Cas12a which anticipates claims 8-9 of the instant application.
Conclusion
No claims are allowable.
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/SARAE L BAUSCH/Primary Examiner, Art Unit 1699