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 .
Preliminary Amendment
The preliminary amendment dated 10/27/2025 has been entered. Claims 1-17, 19-20, and 44 are pending and under examination.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. The earliest possible effective filing date is May 27, 2020 based on the filing date of the provisional application 63/030,796. Cas 13 enzyme sequences (instant claim 44) are disclosed in provisional application 63/194,099 filed on May 27, 2021.
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, 2, 6-9 and 11-12 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Broughton (Nature Biotechnology | VOL 38 | July 2020 | 870–874, Published on line April 16, 2020 – see page 874 IDS citation 18) as evidenced by Chen (Science 15 Feb 2018 Vol 360, Issue 6387 pp. 436-439 IDS citation 22) and NEB (New England Biolabs. Typical RT-LAMP Protocol https://www.neb.com/en-us/protocols/2014/10/09/typical-rt-lamp-protocol. Published in 2014)
Broughton teaches the development and initial validation of a CRISPR–Cas12-based assay for detection of SARS-CoV-2 from extracted patient sample RNA (entire article), (instant claim 1). Figure 1d (below) teaches a schematic drawing depicting the entire method (named DETECTR): from swab to extracted viral RNA to RT-LAMP (with primers for the E and N genes) to Cas 12-based detection of E or N genes, which are visualized by fluorescent ssDNA probe cleavage (instant claim 1(a), 1(b) and 1(c)).
Broughton’s Figure 1d:
PNG
media_image1.png
316
811
media_image1.png
Greyscale
Cas12a enzyme belongs to the Type V class of CRISPR-Cas system and the CRISPR-Cas 12a system works by the Cas12a-crRNA complex binding a dsDNA substrate and generates a nonspecific ssDNA cleavage as evidenced by Chen (figure 1). That is, the Type V class Cas12a effector protein would cleave an RNP containing the RT-LAMP product and a reporter moiety (figure 1d above), (as required in instant claims 1(b), 1(c), 2, and 6). The assay taught by Broughton (right column, second paragraph, page 870. Figure 1d) performs simultaneous reverse transcription and isothermal amplification using loop-mediated amplification (RT–LAMP) for RNA extracted (instant claim 1(a)) from nasopharyngeal or oropharyngeal swabs (as required in instant claim 8 and 9), followed by Cas12 detection of coronavirus sequences (N or E genes), after which cleavage of a reporter molecule (reads on an activatable ssDNA oligonucleotide comprising a reporter moiety (instant claim 1(b)(ii)) confirms detection of the virus (instant claim 1(c)). The designed primers in this assay target the E (envelope) and N (nucleoprotein) genes of SARS-CoV-2 (instant claim 1(a)), Broughton also teaches the Cas12 enzyme being the LbCas12a (instant claims 7 and 12) and that the RT–LAMP was prepared as suggested by a protocol taught by NEB (instant claims 11 (see below), and instant claim 13), (DETECTR assay, page 875).
The protocol taught by NEB used by Broughton includes their WarmStart® DNA polymerase and WarmStart® Reverse transcriptase (instant claim 11) as evidenced by the NEB brochure.
Therefore, the reference teachings anticipate the claimed invention.
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 1-12, are rejected under 35 U.S.C. 103 as being unpatentable over Broughton in view of MN908947 (GenBank: MN908947.1 VRL 12-Jan-2020, https://www.ncbi.nlm.nih.gov/nuccore/MN908947.1)
Broughton teachings have been described above and applied herein. In addition, Broughton teaches the use of PrimerExplorer v.5 software (https://primerexplorer.jp/e/) to design LAMP primers for SARS-CoV-2 against regions of the N gene and E gene using all SARS-CoV-2 sequences available from GISAID25 as of 27 January 2020 (since the first SARS-CoV-2 virus was made public on January 12, 2020 (MN908947.1), GISAID25 included MN908947.1), (Methods, Nucleic acid preparation section). The instant application discloses the use of PrimerExplorer v5 to design the claimed primers targeting several regions of the N gene and E gene of the SARS-CoV-2 genome (GenBank accession number MN908947) (page 59, Design and screening of LAMP primers section (line 20) (instant claims 3-5 and 10). Broughton also teaches that the LAMP primers were added to the RT-LAPM assay at a final concentration of 0.2 μM for F3 and B3, 1.6 μM for forward inner and backward inner primers and 0.8 μM for loop forward and loop backward primers. Reactions were performed independently for N gene, E gene and RNase P (control) using 2 μl of input RNA at 62 °C for 20–30 min (page 875, DETECTR assays section), (instant claim 10).
MN908947 teaches the SARS-CoV-2 isolate Wuhan-Hu-1, complete genome and the claimed primers are found in the viral genome. See examples below:
F3-N3-1 (SEQ ID NO: 17): ccgaagagct accagacgaa
PNG
media_image2.png
103
927
media_image2.png
Greyscale
B3-N3-1 (SEQ ID NO: 18): tgtagcacgattgcagcatt
Complementary reverse sequence: aatgctgcaa tcgtgctaca
PNG
media_image3.png
102
934
media_image3.png
Greyscale
LF-N3-1 (SEQ ID NO: 21): agaaatacca tcttggactg ag
Complementary reverse sequence: ctcagtccaa gatggtattt ct
PNG
media_image4.png
113
966
media_image4.png
Greyscale
LB-N3-1 (SEQ ID NO: 22): actgagggag ccttgaatac ac
PNG
media_image5.png
120
942
media_image5.png
Greyscale
One of ordinary skill in the art would have been motivated to combine the teachings of Broughton and MN908947 to develop a RT-LAMP/CRISPR-Cas12 system and to find primers for the specific detection of SARS-CoV-2 N and E genes (as taught by Broughton). It would further be obvious to use the SARS-CoV-2 sequence as first published on MN908947 in combination with PrimerExplorer v5 to develop effective primers. using these tools as required by instant claims 3-5 and 10. One of ordinary skill would have been motivated to do so because software like PrimerExplorer v5 have been specifically developed for the purpose of primer optimization. There would be a reasonable expectation of success because PrimerExplorer v5 is known to make the process of designing highly specific primers very simple and effective.
It would further be obvious that the primer concentrations in a reaction, the reaction time and temperature or other reaction conditions are clearly a result effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ. It would have been customary for an artisan of ordinary skill to determine the optimal amount of each ingredient needed to achieve the desired results. The principle of law states from MPEP 2144.05: "The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages." (Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382); Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 2.
From the combined teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Claims 1, 7, 13-17 and 19-20 are rejected under 35 U.S.C. 103 as being unpatentable over Broughton in view of Wang (ACS Sensors April 27, 2020 5 (5), 1427-1435 IDS citation 94) and Teng (Genome Biol. 2019, 20 (1), 132).
Broughton teachings have been described above and applied herein.
Broughton does not teach the use of Cas12b (instant claims 7 and 13) or Cas13 enzymes (instant claim 20), the use of a fluorophore-quencher pair (instant claims 14-17) or that the method is performed in the same container (instant claim 19).
Wang teaches a one-pot toolbox, based on Cas12a/crRNA, that enables rapid foodborne pathogen detection at attomolar level (entire article). This one-pot detection means that the reagents, crRNA, and ssDNA-FQ reporter are all in one tube (which reads on same container as required by instant claim 19). Wand also teaches the design of a specific crRNA probe, cleaved by Cas12a upon binding to the target substrate and the dual-labeled reporter (fluorophore and quencher) will be cleaved and the separated fluorophore can emit fluorescence which can be measured under a microplate reader (page1427 last paragraph, figure 1, Cas12a/crRNA Nucleic Acid Detection Section page1429), (instant claims 14-17). Wang teaches that Cas12 and Cas13 are among the Cas enzyme family reported to generate collateral cleavage on DNA and RNA, respectively (page 1427 second column second paragraph) (as recited in instant claim 20 (c)(i) and 20(d)).
Wang does not teach the use of a Cas12b enzyme (instant claims 7 and 13).
Teng teaches a CRISPR-Cas12b-based DNA detection with sub-attomolar sensitivity and single-base specificity (entire article). In addition, it teaches a previously reported AacCas12b protein with loop-mediated isothermal amplification (LAMP). Teng’s work, together with the AacCas12b-based work demonstrates that Cas12b-based nucleic acid detection method should be a feasible platform for molecular diagnostics (page 4 second column, second paragraph), (instant claims 7 and 13).
One of ordinary skill in the art would have been motivated to combine the teachings of Broughton with Wang to develop a RT-LAMP/CRISPR-Cas12 system for SARS-CoV-2 detection and incorporate a dual-labeled reporter (fluorophore and quencher) to be cleaved so fluorescence can be measured. It would further be obvious to combine the teachings of Broughton and Wang with Teng and test different enzymes including Cas12a and Cas12b (such as AacCas12b) or Cas13 to optimize the method. One of ordinary skill would have been motivated to do so because having a reliable detection system, and some flexibility regarding which enzyme to use, is needed for a consistent RT-LAMP/CRISPR-Cas system. There would be a reasonable expectation of success because the dual-labeled reporter (fluorophore and quencher) has been shown to be very effective at providing accurate results, and several Cas
From the combined teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Claims 1, 20 and 44 are rejected under 35 U.S.C. 103 as being unpatentable over Broughton in view of Blake (US2023/0183783 A1; with provisional application No. 63/038,710, filed on June 12,2020) and Zhang ( US2023/0025039 A1, with provisional application No. 62/905,645 filed on 09/25/2019)
Broughton teachings have been described above and applied herein.
Broughton does not teach the sequences of any Cas enzyme.
Blake teaches a detection method comprising steps of: contacting a CRISPR-Cas complex comprising: a Cas protein with collateral cleavage activity; and a guide RNA selected or engineered to be complementary to a target sequence; with a sample comprising the target sequence (claim1), (instant claims 1, 20 and 44). One of these Cas proteins includes a TccCAs13a Thermoclostridium caenicola (a Cas13 enzyme as required by instant claim 20 and 44) identified by SEQ ID NO: 1 [0086] which is 100% identical to the instant application SEQ ID NO: 67 recited in instant claim 44, see alignment below.
Zhang teaches novel Type VI CRISPR enzymes including Cas 13 (instant claims 22 and 44) defined in SEQ ID NO: 4663 (claim 2) which is 100% identical to instant SEQ ID NO; 68 recited in instant claim 44, see alignment below.
SEQUENCE ALIGNMENT FOR SEQ ID NO: 67
Title: US-18-000-055-67
Perfect score: 6359
Sequence: 1 MKITKRKWGEHHPPLYFYRD..........PSHGERFIDTLKALMVYPRG 1225
US-17-795-815-1
(NOTE: this sequence has 4 duplicates in the database searched)
Sequence 1, US/17795815
Publication No. US20230183783A1
GENERAL INFORMATION
APPLICANT: SHERLOCK BIOSCIENCES
TITLE OF INVENTION: IMPROVED DETECTION ASSAYS
FILE REFERENCE: 2013065-0427
CURRENT APPLICATION NUMBER: US/17/795,815
CURRENT FILING DATE: 2022-07-27
PRIOR APPLICATION NUMBER: PCT/US21/15306
PRIOR FILING DATE: 2021-01-27
PRIOR APPLICATION NUMBER: 63/139,267
PRIOR FILING DATE: 2021-01-19
PRIOR APPLICATION NUMBER: 63/038,710
PRIOR FILING DATE: 2020-06-12
PRIOR APPLICATION NUMBER: 62/970,159
PRIOR FILING DATE: 2020-02-04
PRIOR APPLICATION NUMBER: 62/967,536
PRIOR FILING DATE: 2020-01-29
PRIOR APPLICATION NUMBER: 62/966,527
PRIOR FILING DATE: 2020-01-27
NUMBER OF SEQ ID NOS: 294
SEQ ID NO 1
LENGTH: 1225
TYPE: PRT
ORGANISM: Thermoclostridium caenicola
Query Match 100.0%; Score 6359; Length 1225;
Best Local Similarity 100.0%;
Matches 1225; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MKITKRKWGEHHPPLYFYRDEDSGRLLAQNDRKQDYTDTLFNDIAQDTFERSLRNRLLKT
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MKITKRKWGEHHPPLYFYRDEDSGRLLAQNDRKQDYTDTLFNDIAQDTFERSLRNRLLKT
Qy 61 PEKGDKRFYSNEIVKLVEKLCQGADVAEIMKSMERNEKLRPKNEKEIKNLKKQLDGTLSE
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 PEKGDKRFYSNEIVKLVEKLCQGADVAEIMKSMERNEKLRPKNEKEIKNLKKQLDGTLSE
Qy 121 YGKRYTAPEGAMTLNDALFYLVEGNPLKQAMAKAELGKIREALIKEKENRINRVRYSIKN
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 YGKRYTAPEGAMTLNDALFYLVEGNPLKQAMAKAELGKIREALIKEKENRINRVRYSIKN
Qy 181 NKIPLRIQEDGGITPNNDRAAWLLGLMKPADPAKGITDCYPLLGELEEVFDFDKLSKTLH
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 NKIPLRIQEDGGITPNNDRAAWLLGLMKPADPAKGITDCYPLLGELEEVFDFDKLSKTLH
Qy 241 EKISRCQGRPRSIAMAVDEALKQYLRELWEKSPSRQQDLKYYFQAVQEYFKDNFPIRTKR
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 EKISRCQGRPRSIAMAVDEALKQYLRELWEKSPSRQQDLKYYFQAVQEYFKDNFPIRTKR
Qy 301 MGARLRQELLKDKTSLSRLLEPKHMANAVRRRLINQSTQMHILYGKLYAYCCGEDGRLLV
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 MGARLRQELLKDKTSLSRLLEPKHMANAVRRRLINQSTQMHILYGKLYAYCCGEDGRLLV
Qy 361 NSETLQRIQVHEAVKKQAMTAVLWSISRLRYFYQFEDGDILSNKNPIKDFRDKFLRDTNK
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 NSETLQRIQVHEAVKKQAMTAVLWSISRLRYFYQFEDGDILSNKNPIKDFRDKFLRDTNK
Qy 421 YTHEDVEACKEKLQDFFPLKELQEKIKEDAKGLQETDNKQADTTDFKAIGHIVRDDRKLC
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 YTHEDVEACKEKLQDFFPLKELQEKIKEDAKGLQETDNKQADTTDFKAIGHIVRDDRKLC
Qy 481 NQLLAECVSCIGELRHHIFHYKNVTLIQALKRIADKVKPEDLSVLRAIYLLDRRNLKKAF
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 NQLLAECVSCIGELRHHIFHYKNVTLIQALKRIADKVKPEDLSVLRAIYLLDRRNLKKAF
Qy 541 AKRISSMNLPLYYREDLLSRIFKKEGTAFFLYSAKIQMTPSFQRVYERGKNLRREFECER
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 AKRISSMNLPLYYREDLLSRIFKKEGTAFFLYSAKIQMTPSFQRVYERGKNLRREFECER
Qy 601 MKAEASNGQNGQDGDRLKWFRQLAAGDSADTHFNWAVEAYAESAADVENNVEFDTDVDAQ
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 601 MKAEASNGQNGQDGDRLKWFRQLAAGDSADTHFNWAVEAYAESAADVENNVEFDTDVDAQ
Qy 661 RALRNLLLLIYRHHFLPEVQKDETLVTGKIHKVLERNRQLSEGQGPNQGKAHGYSVIEEL
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 661 RALRNLLLLIYRHHFLPEVQKDETLVTGKIHKVLERNRQLSEGQGPNQGKAHGYSVIEEL
Qy 721 YHEGMPLSDLMKQLQRRISETERESRELAQEKTDYAQRFILDIFAEAFNDFLEAHYGEEY
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 721 YHEGMPLSDLMKQLQRRISETERESRELAQEKTDYAQRFILDIFAEAFNDFLEAHYGEEY
Qy 781 LEIMSPRKDAEAAKKWVKESKTVDLKTSIDEKEPEGHLLVLYPVLRLLDERELGELQQQM
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 781 LEIMSPRKDAEAAKKWVKESKTVDLKTSIDEKEPEGHLLVLYPVLRLLDERELGELQQQM
Qy 841 IRYRTSLASWQGESNFSEEIRIAGQIEELTELVKLTEPEPQFAEEVWGKRAKEAFEDFIE
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 841 IRYRTSLASWQGESNFSEEIRIAGQIEELTELVKLTEPEPQFAEEVWGKRAKEAFEDFIE
Qy 901 GNMKNYEAFYLQSDNNTPVYRRNMSRLLRSGLMGVYQKVLASHKQALKRDYLLWSEKHWN
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 901 GNMKNYEAFYLQSDNNTPVYRRNMSRLLRSGLMGVYQKVLASHKQALKRDYLLWSEKHWN
Qy 961 VKDENGADISSAEQAQCLLQRLHRKYAESPSRFTEEDCKLYEKVLRRLEDYNQAVKNLSF
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 961 VKDENGADISSAEQAQCLLQRLHRKYAESPSRFTEEDCKLYEKVLRRLEDYNQAVKNLSF
Qy 1021 SSLYEICVLNLEILSRWVGFVQDWERDMYFLLLAWVRQGKLDGIKEEDVRDIFSEGNIIR
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1021 SSLYEICVLNLEILSRWVGFVQDWERDMYFLLLAWVRQGKLDGIKEEDVRDIFSEGNIIR
Qy 1081 NLVDTLKGENMNAFESVYFPENKGSKYLGVRNDVAHLDLMRKNGWRLEAGKTCSVMEDYI
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1081 NLVDTLKGENMNAFESVYFPENKGSKYLGVRNDVAHLDLMRKNGWRLEAGKTCSVMEDYI
Qy 1141 NRLRFLLSYDQKRMNAVTKTLQQIFDRHKVKIRFTVEKGGMLKIEDVTADKIVHLKGSRL
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1141 NRLRFLLSYDQKRMNAVTKTLQQIFDRHKVKIRFTVEKGGMLKIEDVTADKIVHLKGSRL
Qy 1201 SGIEIPSHGERFIDTLKALMVYPRG 1225
|||||||||||||||||||||||||
Db 1201 SGIEIPSHGERFIDTLKALMVYPRG 1225
SEQUENCE ALIGNMENT FOR SEQ ID NO: 68
Title: US-18-000-055-68
Perfect score: 4623
Sequence: 1 MGIDYSLTSDCYRGINKSCF..........YFPIVERKDDTKKRRDKKQK 873
US-17-761-292-4663
Sequence 4663, US/17761292
Publication No. US20230025039A1
GENERAL INFORMATION
APPLICANT: The Broad Institute, Inc.
APPLICANT: Massachusetts Institute of Technology
APPLICANT: Zhang, Feng
APPLICANT: Altae-Tran, Han
APPLICANT: Kannan, Soumya
TITLE OF INVENTION: Novel Type VI CRISPR Enzymes and Systems
FILE REFERENCE: BROD-4860WP
CURRENT APPLICATION NUMBER: US/17/761,292
CURRENT FILING DATE: 2022-03-17
PRIOR APPLICATION NUMBER: US 62/903,604
PRIOR FILING DATE: 2019-09-20
PRIOR APPLICATION NUMBER: US 62/905,645
PRIOR FILING DATE: 2019-09-25
PRIOR APPLICATION NUMBER: US 62/967,408
PRIOR FILING DATE: 2020-01-29
PRIOR APPLICATION NUMBER: US 63/044,190
PRIOR FILING DATE: 2020-06-25
NUMBER OF SEQ ID NOS: 6066
SEQ ID NO 4663
LENGTH: 873
TYPE: PRT
ORGANISM: Artificial
FEATURE:
OTHER INFORMATION: Synthetic
Query Match 100.0%; Score 4623; Length 873;
Best Local Similarity 100.0%;
Matches 873; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MGIDYSLTSDCYRGINKSCFAVALNIAYDNCDHKGCRTLLSEVLRSKGGISDEQIKSQVV
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MGIDYSLTSDCYRGINKSCFAVALNIAYDNCDHKGCRTLLSEVLRSKGGISDEQIKSQVV
Qy 61 DGIQKRLKDIRNYFSHYYHAEDCLRFGDQDAVKVFLEEIYKNAESKTVGATKESDYKGVV
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 DGIQKRLKDIRNYFSHYYHAEDCLRFGDQDAVKVFLEEIYKNAESKTVGATKESDYKGVV
Qy 121 PPLFELHNGTYMITAAGVIFLASFFCHRSNVYRMLGAVKGFKHTGKEQLSDGQKRDYGFT
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 PPLFELHNGTYMITAAGVIFLASFFCHRSNVYRMLGAVKGFKHTGKEQLSDGQKRDYGFT
Qy 181 RRLLAYYALRDSYSVGAEDKTRCFREILSYLSRVPQLAVDWLNEQQLLTPEEKEAFLNQP
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 RRLLAYYALRDSYSVGAEDKTRCFREILSYLSRVPQLAVDWLNEQQLLTPEEKEAFLNQP
Qy 241 AEDEGGDISDSSSSDKNKKSKEKRRSLRRDEKFILFAIQFIEGWAAEQGLDVTFARYQKT
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 AEDEGGDISDSSSSDKNKKSKEKRRSLRRDEKFILFAIQFIEGWAAEQGLDVTFARYQKT
Qy 301 VEKAENKNQDGKQARAVQLKYRNQGLNPDFNNEWMYYIQNEHAIIQIKLNNKKAVAARIS
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 VEKAENKNQDGKQARAVQLKYRNQGLNPDFNNEWMYYIQNEHAIIQIKLNNKKAVAARIS
Qy 361 ENELKYLVLLIFEEKGNDAVQKLNCYIYSMSQKIEGEWKHRPEDERWMPSFTKRADRTVT
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 ENELKYLVLLIFEEKGNDAVQKLNCYIYSMSQKIEGEWKHRPEDERWMPSFTKRADRTVT
Qy 421 PEAVQSRLSYIRKQLQETIEKIGQEEPRNNKWLIYKGKKISMILKFISDSIRDIQRRPNV
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 PEAVQSRLSYIRKQLQETIEKIGQEEPRNNKWLIYKGKKISMILKFISDSIRDIQRRPNV
Qy 481 KQYHILRDALQRLDFDGFYKELQNYVNDGRIAVSLYDQIKGVNDISGLCKKVCELTLERL
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 KQYHILRDALQRLDFDGFYKELQNYVNDGRIAVSLYDQIKGVNDISGLCKKVCELTLERL
Qy 541 AGLEAKNGSELRRYIGLEAQEKHPKYGEWNTLQEKAKRFLESQFSIGKNFLRKMFYGDCC
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 AGLEAKNGSELRRYIGLEAQEKHPKYGEWNTLQEKAKRFLESQFSIGKNFLRKMFYGDCC
Qy 601 QKRCFDEEKGYNTQAKERKSLYSIVKEKLKDIKPIHDDRWYLIDRNPKNYDNKHSRIIRQ
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 601 QKRCFDEEKGYNTQAKERKSLYSIVKEKLKDIKPIHDDRWYLIDRNPKNYDNKHSRIIRQ
Qy 661 MCNTYIQDVLCMKMAMWHYEKLISATEFRNKLEWNCIGQGNMGYERYSLWYKTGCGVVIQ
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 661 MCNTYIQDVLCMKMAMWHYEKLISATEFRNKLEWNCIGQGNMGYERYSLWYKTGCGVVIQ
Qy 721 FTPADFLRLDIIEKPAMIENICQCFVLGNKKLNSGAEKKITWDKFNKDGIAKYRKRQAEA
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 721 FTPADFLRLDIIEKPAMIENICQCFVLGNKKLNSGAEKKITWDKFNKDGIAKYRKRQAEA
Qy 781 VRAIFAFEEGLKIQEDKWSHERYFPFCNILDEAVKQGKIKDTGKDKEALNRGRNDFFHEE
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 781 VRAIFAFEEGLKIQEDKWSHERYFPFCNILDEAVKQGKIKDTGKDKEALNRGRNDFFHEE
Qy 841 FKSTEDQQAIFQKYFPIVERKDDTKKRRDKKQK 873
|||||||||||||||||||||||||||||||||
Db 841 FKSTEDQQAIFQKYFPIVERKDDTKKRRDKKQK 873
One of ordinary skill in the art would have been motivated to combine the teachings of Broughton with Blake and Zhang to develop a RT-LAMP/CRISPR-Cas system for SARS-CoV-2 detection and test the Cas13 enzymes claimed by Blake and Zhang. to optimize the method. One of ordinary skill would have been motivated to do so because these CAS 13 enzymes have been successfully characterized. There would be a reasonable expectation of success because these Cas 13 enzymes have been shown to effectively work in the CRISPR-Cas system..
From the combined teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
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.
Claim 44 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 12, 13-15, 18 and 27 of patent application No US 2025/0270663 A1 (US 18/564,572) (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of US 2025/0270663 A1 are drawn to the same Cas 13 effector protein as disclosed in this instant application and as demonstrated by the sequence alignments below and related methods of use for these Cas 13 effector proteins.
Sequence alignment for instant claim 44 SEQ ID NO: 67 compared to SEQ ID NO: 64 (reference application). (Note: SEQ ID NO: 63 discloses the polynucleotide encoding SEQ ID: 64):
Title: US-18-000-055-67
Perfect score: 6359
Sequence: 1 MKITKRKWGEHHPPLYFYRD..........PSHGERFIDTLKALMVYPRG 1225
Database : US-18-564-572-64.pep:*
%
Result Query
No. Score Match Length DB ID Description
----------------------------------------------------------------------------
1 6359 100.0 1225 1 US-18-564-572-64 CAS13-BASED COMPOS
ALIGNMENTS
US-18-564-572-64
Query Match 100.0%; Score 6359; DB 1; Length 1225;
Best Local Similarity 100.0%;
Matches 1225; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MKITKRKWGEHHPPLYFYRDEDSGRLLAQNDRKQDYTDTLFNDIAQDTFERSLRNRLLKT 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MKITKRKWGEHHPPLYFYRDEDSGRLLAQNDRKQDYTDTLFNDIAQDTFERSLRNRLLKT 60
Qy 61 PEKGDKRFYSNEIVKLVEKLCQGADVAEIMKSMERNEKLRPKNEKEIKNLKKQLDGTLSE
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 PEKGDKRFYSNEIVKLVEKLCQGADVAEIMKSMERNEKLRPKNEKEIKNLKKQLDGTLSE
Qy 121 YGKRYTAPEGAMTLNDALFYLVEGNPLKQAMAKAELGKIREALIKEKENRINRVRYSIKN
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 YGKRYTAPEGAMTLNDALFYLVEGNPLKQAMAKAELGKIREALIKEKENRINRVRYSIKN
Qy 181 NKIPLRIQEDGGITPNNDRAAWLLGLMKPADPAKGITDCYPLLGELEEVFDFDKLSKTLH
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 NKIPLRIQEDGGITPNNDRAAWLLGLMKPADPAKGITDCYPLLGELEEVFDFDKLSKTLH
Qy 241 EKISRCQGRPRSIAMAVDEALKQYLRELWEKSPSRQQDLKYYFQAVQEYFKDNFPIRTKR
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 EKISRCQGRPRSIAMAVDEALKQYLRELWEKSPSRQQDLKYYFQAVQEYFKDNFPIRTKR
Qy 301 MGARLRQELLKDKTSLSRLLEPKHMANAVRRRLINQSTQMHILYGKLYAYCCGEDGRLLV
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 MGARLRQELLKDKTSLSRLLEPKHMANAVRRRLINQSTQMHILYGKLYAYCCGEDGRLLV
Qy 361 NSETLQRIQVHEAVKKQAMTAVLWSISRLRYFYQFEDGDILSNKNPIKDFRDKFLRDTNK
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 NSETLQRIQVHEAVKKQAMTAVLWSISRLRYFYQFEDGDILSNKNPIKDFRDKFLRDTNK
Qy 421 YTHEDVEACKEKLQDFFPLKELQEKIKEDAKGLQETDNKQADTTDFKAIGHIVRDDRKLC
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 YTHEDVEACKEKLQDFFPLKELQEKIKEDAKGLQETDNKQADTTDFKAIGHIVRDDRKLC
Qy 481 NQLLAECVSCIGELRHHIFHYKNVTLIQALKRIADKVKPEDLSVLRAIYLLDRRNLKKAF
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 NQLLAECVSCIGELRHHIFHYKNVTLIQALKRIADKVKPEDLSVLRAIYLLDRRNLKKAF
Qy 541 AKRISSMNLPLYYREDLLSRIFKKEGTAFFLYSAKIQMTPSFQRVYERGKNLRREFECER
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 AKRISSMNLPLYYREDLLSRIFKKEGTAFFLYSAKIQMTPSFQRVYERGKNLRREFECER
Qy 601 MKAEASNGQNGQDGDRLKWFRQLAAGDSADTHFNWAVEAYAESAADVENNVEFDTDVDAQ
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 601 MKAEASNGQNGQDGDRLKWFRQLAAGDSADTHFNWAVEAYAESAADVENNVEFDTDVDAQ
Qy 661 RALRNLLLLIYRHHFLPEVQKDETLVTGKIHKVLERNRQLSEGQGPNQGKAHGYSVIEEL
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 661 RALRNLLLLIYRHHFLPEVQKDETLVTGKIHKVLERNRQLSEGQGPNQGKAHGYSVIEEL 720
Qy 721 YHEGMPLSDLMKQLQRRISETERESRELAQEKTDYAQRFILDIFAEAFNDFLEAHYGEEY
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 721 YHEGMPLSDLMKQLQRRISETERESRELAQEKTDYAQRFILDIFAEAFNDFLEAHYGEEY
Qy 781 LEIMSPRKDAEAAKKWVKESKTVDLKTSIDEKEPEGHLLVLYPVLRLLDERELGELQQQM
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 781 LEIMSPRKDAEAAKKWVKESKTVDLKTSIDEKEPEGHLLVLYPVLRLLDERELGELQQQM
Qy 841 IRYRTSLASWQGESNFSEEIRIAGQIEELTELVKLTEPEPQFAEEVWGKRAKEAFEDFIE
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 841 IRYRTSLASWQGESNFSEEIRIAGQIEELTELVKLTEPEPQFAEEVWGKRAKEAFEDFIE 900
Qy 901 GNMKNYEAFYLQSDNNTPVYRRNMSRLLRSGLMGVYQKVLASHKQALKRDYLLWSEKHWN
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 901 GNMKNYEAFYLQSDNNTPVYRRNMSRLLRSGLMGVYQKVLASHKQALKRDYLLWSEKHWN
Qy 961 VKDENGADISSAEQAQCLLQRLHRKYAESPSRFTEEDCKLYEKVLRRLEDYNQAVKNLSF
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 961 VKDENGADISSAEQAQCLLQRLHRKYAESPSRFTEEDCKLYEKVLRRLEDYNQAVKNLSF
Qy 1021 SSLYEICVLNLEILSRWVGFVQDWERDMYFLLLAWVRQGKLDGIKEEDVRDIFSEGNIIR
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1021 SSLYEICVLNLEILSRWVGFVQDWERDMYFLLLAWVRQGKLDGIKEEDVRDIFSEGNIIR
Qy 1081 NLVDTLKGENMNAFESVYFPENKGSKYLGVRNDVAHLDLMRKNGWRLEAGKTCSVMEDYI
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1081 NLVDTLKGENMNAFESVYFPENKGSKYLGVRNDVAHLDLMRKNGWRLEAGKTCSVMEDYI
Qy 1141 NRLRFLLSYDQKRMNAVTKTLQQIFDRHKVKIRFTVEKGGMLKIEDVTADKIVHLKGSRL
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1141 NRLRFLLSYDQKRMNAVTKTLQQIFDRHKVKIRFTVEKGGMLKIEDVTADKIVHLKGSRL
Qy 1201 SGIEIPSHGERFIDTLKALMVYPRG 1225
|||||||||||||||||||||||||
Db 1201 SGIEIPSHGERFIDTLKALMVYPRG 1225
Sequence alignment results (alignment not shown) for instant claim 44 SEQ ID NO: 68 compared to SEQ ID NO: 66 (reference application). (Note: SEQ ID NO: 65 discloses the polynucleotide encoding SEQ ID: 66).
Title: US-18-000-055-68
Perfect score: 4623
Sequence: 1 MGIDYSLTSDCYRGINKSCF..........YFPIVERKDDTKKRRDKKQK 873
Database : US-18-564-572-66.pep:*
%
Result Query
No. Score Match Length DB ID Description
----------------------------------------------------------------------------
1 4623 100.0 873 1 US-18-564-572-66 CAS13-BASED COMPOS
US-18-564-572-66
Query Match 100.0%; Score 4623; DB 1; Length 873;
Best Local Similarity 100.0%;
Matches 873; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Sequence alignment results (alignment not shown) for instant claim 44 SEQ ID NO: 95 compared to SEQ ID NO: 68 (reference application). (Note: SEQ ID NO: 67 discloses the polynucleotide encoding SEQ ID: 68).
Title: US-18-000-055-95
Perfect score: 6752
Sequence: 1 MKLTRRRISGNSVDQKITAA..........NLFKFDYEDKNKSSANPKHT 1285
Database : US-18-564-572-68.pep:*
%
Result Query
No. Score Match Length DB ID Description
----------------------------------------------------------------------------
1 6752 100.0 1285 1 US-18-564-572-68 CAS13-BASED COMPOS
US-18-564-572-68
Query Match 100.0%; Score 6752; DB 1; Length 1285;
Best Local Similarity 100.0%;
Matches 1285; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to IMMA BARRERA whose telephone number is (571) 272-0674. The examiner can normally be reached Monday - Friday 9 to 5.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Janet Andres can be reached on (571) 272-0867. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/IMMA BARRERA/
Examiner, Art Unit 1671
/JANET L ANDRES/Supervisory Patent Examiner, Art Unit 1671