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 .
Claim Status
Claims 1-21 are pending and examined on the merits.
Claim 1, 6, 17, 19-21 are currently amended.
Claim Rejections - 35 USC § 112
Response to Arguments - Improper Claim Dependency
Applicant’s amendments filed 22 January 2026 have overcome the rejection of record.
Claim Rejections - 35 USC § 112
Indefiniteness
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.
Claims 6, 8-12, 16, 18, and 20-21 are 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 pre-AIA the applicant regards as the invention.
Claim 6 has been amended to include item (A) which requires that the amino acid sequence be at least 98% identical to SEQ ID NO:9. However, item (B) still recites that the amino acid sequence only needs to be 95% identical to SEQ ID NO:9. Given this direct conflict, the metes and bounds of the claims cannot be determined. Claims 8-12, 16, 18, 20-21 are rejected for depending from an indefinite claim and failing to recite additional limitations that would render the claim definite. Note that claims 20-21 have the same issue occurring via item (ii).
Claim Rejections - 35 USC § 103
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim(s) 6, 8-10, 12, 18, and 20-21 remain rejected under 35 U.S.C. 103 as being unpatentable over Doudna (US10253365 B1), and further in view of Kleinstiver et al 2019 (Nature Biotechnology 37:3, p.276-282).
Doudna et al teach Mb3Cas12a CRISPR nucleases including SEQ ID NO:7 which is 97.4% identical to instant SEQ ID NO:9 (alignment below). They also teach that the targeting RNA sequence for this CRISPR nuclease comprises the same sequence as instant SEQ ID NO:17 (Figure 2). They teach host cells including plant cells and seeds comprising the Cpf1 enzymes and methods of modifying host cell genomes.
Doudna et al do not teach any of the specific mutations recited in claim 1.
Kleinstiver et al teach engineering of Cas12a variants to alter PAM specificity by mutating E174R/S542R/K548R. The E174R substitution is analogous to the D172R substitution in instant SEQ ID NO:9.
At the time of filing, it would have been prima facie obvious for a person of ordinary skill in the art to substitute D172R in Cpf1 of SEQ ID NO:7 of Doudna et al to the end of altering PAM specificity of the Cpf1 of Doudna et al. In combining these teachings, the resultant Cpf1 would comprise a mutation analogous to D172R and be greater than 97.4% identical to SEQ ID NO:9. It further would have been obvious to carry out the modification at a temperature of less than 32 C because most field crops have ideal growth temperatures at less than 32 C. Accordingly, claims 1-4, 6, 8-12, 16, 18, and 20-21 is/are rejected under 35 U.S.C. 103 as being unpatentable over Doudna et al and further in view of Kleinstiver et al.
Match to Instant SEQ ID NO:9
US-15-897-089A-7
(NOTE: this sequence has 5 duplicates in the database searched.
See complete list at the end of this report)
Sequence 7, US/15897089A
Patent No. 10253365
GENERAL INFORMATION
APPLICANT: Chen, Janice S
APPLICANT: Doudna, Jennifer A
APPLICANT: Harrington, Lucas B
APPLICANT: Ma, Enbo
TITLE OF INVENTION: TYPE V CRISPR/CAS EFFECTOR PROTEINS FOR CLEAVING SSDNAS AND
TITLE OF INVENTION: DETECTING TARGET DNAS
FILE REFERENCE: BERK-375
CURRENT APPLICATION NUMBER: US/15/897,089A
CURRENT FILING DATE: 2018-02-14
PRIOR APPLICATION NUMBER: US 62/590,106
PRIOR FILING DATE: 2017-11-22
PRIOR APPLICATION NUMBER: US 62/626,593
PRIOR FILING DATE: 2018-02-05
NUMBER OF SEQ ID NOS: 179
SEQ ID NO 7
LENGTH: 1269
TYPE: PRT
ORGANISM: Moraxella bovoculi
Query Match 97.4%; Score 6484.5; Length 1269;
Best Local Similarity 97.2%;
Matches 1228; Conservative 21; Mismatches 11; Indels 3; Gaps 1;
Qy 2 LFQDFTHLYPLSKTMRFELKPIGKTLEHIHAKNFLSQDETMADMYQKVKAILDDYHRDFI 61
||||||||||||||:||||||||||||||||||||:||||||||||||||||||||||||
Db 10 LFQDFTHLYPLSKTVRFELKPIGKTLEHIHAKNFLNQDETMADMYQKVKAILDDYHRDFI 69
Qy 62 ADMMGEVKLTKLAEFYDVYLKFRKNPKDDGLQKQLKDLQAVLRKEIVKPIGNGGKYKAGY 121
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 70 ADMMGEVKLTKLAEFYDVYLKFRKNPKDDGLQKQLKDLQAVLRKEIVKPIGNGGKYKAGY 129
Qy 122 DRLFGAKLFKDGKELGDLAKFVIAQEGESSPKLAHLAHFEKFSTYFTGFHRNRKNMYSDE 181
|||||||||||||||||||||||||||||||||||||||||||||||||| |||||||||
Db 130 DRLFGAKLFKDGKELGDLAKFVIAQEGESSPKLAHLAHFEKFSTYFTGFHDNRKNMYSDE 189
Qy 182 DKHTAITYRLIHENLPRFIDNLQILATIKQKHSALYDQIINELTASGLDVSLASHLDGYH 241
|||||| |||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 190 DKHTAIA YRLIHENLPRFIDNLQILATIKQKHSALYDQIINELTASGLDVSLASHLDGYH 249
Qy 242 KLLTQEGITAYNTLLGGISGEAGSRKIQGINELINSHHNQHCHKSERIAKLRPLHKQILS 301
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 250 KLLTQEGITAYNTLLGGISGEAGSRKIQGINELINSHHNQHCHKSERIAKLRPLHKQILS 309
Qy 302 DGMGVSFLPSKFADDSEMCQAVNEFYRHYADVFAKVQSLFDGFDDHQKDGIYVEHKNLNE 361
|||||||||||||||||:|||||||||||||||||||||||||||:||||||||:|||||
Db 310 DGMGVSFLPSKFADDSEVCQAVNEFYRHYADVFAKVQSLFDGFDDYQKDGIYVEYKNLNE 369
Qy 362 LSKQAFGDFALLGRVLDGYYVDVVNPEFNERFAKAKTDNAKAKLTKEKDKFIKGVHSLAS 421
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 370 LSKQAFGDFALLGRVLDGYYVDVVNPEFNERFAKAKTDNAKAKLTKEKDKFIKGVHSLAS 429
Qy 422 LEQAIEHYTARHDDESVQAGKLGQYFKHGLAGVDNPIQKIHNNHSTIKGFLERERPAGER 481
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 430 LEQAIEHYTARHDDESVQAGKLGQYFKHGLAGVDNPIQKIHNNHSTIKGFLERERPAGER 489
Qy 482 ALPKIKSGKNPEMTQLRQLKELLDNALNVAHFAKLLTTKTTLDNQDGNFYGEFGALYDEL 541
||||||| |:|| :|||||||||||||||||||||||||| |||||||||||||||||
Db 490 ALPKIKSDKSPE---IRQLKELLDNALNVAHFAKLLTTKTTLHNQDGNFYGEFGALYDEL 546
Qy 542 AKIPTLYNKVRDYLSQKPFSTEKYKLNFGNPTLLNGWDLNKEKDNFGIILQKDGCYYLAL 601
||| |||||||||||||||||||||||||||||||||||||||||||:||||||||||||
Db 547 AKIATLYNKVRDYLSQKPFSTEKYKLNFGNPTLLNGWDLNKEKDNFGVILQKDGCYYLAL 606
Qy 602 LDKAHKKVFDNAPNTGKNVYQKMIYKLLPGPNKMLPKVFFAKSNLDYYNPSAELLDKYAQ 661
|||||||||||||||||:||||||||||||||||||||||||||||||||||||||||||
Db 607 LDKAHKKVFDNAPNTGKSVYQKMIYKLLPGPNKMLPKVFFAKSNLDYYNPSAELLDKYAQ 666
Qy 662 GTHKKGNNFNLKDCHALIDFFKAGINKHPEWQHFGFKFSPTSSYQDLSDFYREVEPQGYQ 721
||||||:|||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 667 GTHKKGDNFNLKDCHALIDFFKAGINKHPEWQHFGFKFSPTSSYQDLSDFYREVEPQGYQ 726
Qy 722 VKFVDINADYINELVEQGQLYLFQIYNKDFSPKAHGKPNLHTLYFKALFSKDNLANPIYK 781
||||||||||||||||||||||||||||||||||||||||||||||||||:||| |||||
Db 727 VKFVDINADYINELVEQGQLYLFQIYNKDFSPKAHGKPNLHTLYFKALFSEDNLVNPIYK 786
Qy 782 LNGEAQIFYRKASLDMNETTIHRAGEVLENKNPDNPKKRQFVYDIIKDKRYTQDKFMLHV 841
|||||:||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 787 LNGEAEIFYRKASLDMNETTIHRAGEVLENKNPDNPKKRQFVYDIIKDKRYTQDKFMLHV 846
Qy 842 PITMNFGVQGMTIKEFNKKVNQSIQQYDEVNVIGIDRGERHLLYLTVINSKGEILEQRSL 901
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 847 PITMNFGVQGMTIKEFNKKVNQSIQQYDEVNVIGIDRGERHLLYLTVINSKGEILEQRSL 906
Qy 902 NDITTASANGTQMTTPYHKILDKREIERLNARVGWGEIETIKELKSGYLSHVVHQISQLM 961
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 907 NDITTASANGTQMTTPYHKILDKREIERLNARVGWGEIETIKELKSGYLSHVVHQISQLM 966
Qy 962 LKYNAIVVLEDLNFGFKRGRFKVEKQIYQNFENALIKKLNHLVLKDEADDEIGSYKNALQ 1021
||||||||||||||||||||||||||||||||||||||||||||||:|||||||||||||
Db 967 LKYNAIVVLEDLNFGFKRGRFKVEKQIYQNFENALIKKLNHLVLKDKADDEIGSYKNALQ 1026
Qy 1022 LTNNFTDLKSIGKQTGFLFYVPAWNTSKIDPETGFVDLLKPRYENIAQSQAFFGKFDKIC 1081
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1027 LTNNFTDLKSIGKQTGFLFYVPAWNTSKIDPETGFVDLLKPRYENIAQSQAFFGKFDKIC 1086
Qy 1082 YNADKDYFEFHIDYAKFTDKAKNSRQIWKICSHGDKRYVYDKTANQNKGATKGINVNDEL 1141
||||: ||||||||||| ||||||||||||||||||||||||||||||||| |:||||||
Db 1087 YNADRGYFEFHIDYAKFNDKAKNSRQIWKICSHGDKRYVYDKTANQNKGATIGVNVNDEL 1146
Qy 1142 KSLFARHHINDKQPNLVMDICQNNDKEFHKSLIYLLKTLLALRYSNASSDEDFILSPVAN 1201
|||| |:|||||||||||||||||||||||||:|||||||||||||||||||||||||||
Db 1147 KSLFTRYHINDKQPNLVMDICQNNDKEFHKSLMYLLKTLLALRYSNASSDEDFILSPVAN 1206
Qy 1202 DEGMFFNSALADDTQPQNADANGAYHIALKGLWVLEQIKNSDDLNKVKLAIDNQTWLNFA 1261
|||:|||||||||||||||||||||||||||||:| ::||||||||||||||||||||||
Db 1207 DEGVFFNSALADDTQPQNADANGAYHIALKGLWLLNELKNSDDLNKVKLAIDNQTWLNFA 1266
Qy 1262 QNR 1264
|||
Db 1267 QNR 1269
Match to instant SEQ ID NO:3
US-15-897-089A-7
(NOTE: this sequence has 5 duplicates in the database searched.
See complete list at the end of this report)
Sequence 7, US/15897089A
Patent No. 10253365
GENERAL INFORMATION
APPLICANT: Chen, Janice S
APPLICANT: Doudna, Jennifer A
APPLICANT: Harrington, Lucas B
APPLICANT: Ma, Enbo
TITLE OF INVENTION: TYPE V CRISPR/CAS EFFECTOR PROTEINS FOR CLEAVING SSDNAS AND
TITLE OF INVENTION: DETECTING TARGET DNAS
FILE REFERENCE: BERK-375
CURRENT APPLICATION NUMBER: US/15/897,089A
CURRENT FILING DATE: 2018-02-14
PRIOR APPLICATION NUMBER: US 62/590,106
PRIOR FILING DATE: 2017-11-22
PRIOR APPLICATION NUMBER: US 62/626,593
PRIOR FILING DATE: 2018-02-05
NUMBER OF SEQ ID NOS: 179
SEQ ID NO 7
LENGTH: 1269
TYPE: PRT
ORGANISM: Moraxella bovoculi
Query Match 97.5%; Score 6492.5; Length 1269;
Best Local Similarity 97.3%;
Matches 1229; Conservative 21; Mismatches 10; Indels 3; Gaps 1;
Qy 2 LFQDFTHLYPLSKTMRFELKPIGKTLEHIHAKNFLSQDETMADMYQKVKAILDDYHRDFI 61
||||||||||||||:||||||||||||||||||||:||||||||||||||||||||||||
Db 10 LFQDFTHLYPLSKTVRFELKPIGKTLEHIHAKNFLNQDETMADMYQKVKAILDDYHRDFI 69
Qy 62 ADMMGEVKLTKLAEFYDVYLKFRKNPKDDGLQKQLKDLQAVLRKEIVKPIGNGGKYKAGY 121
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 70 ADMMGEVKLTKLAEFYDVYLKFRKNPKDDGLQKQLKDLQAVLRKEIVKPIGNGGKYKAGY 129
Qy 122 DRLFGAKLFKDGKELGDLAKFVIAQEGESSPKLAHLAHFEKFSTYFTGFHDNRKNMYSDE 181
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 130 DRLFGAKLFKDGKELGDLAKFVIAQEGESSPKLAHLAHFEKFSTYFTGFHDNRKNMYSDE 189
Qy 182 DKHTAITYRLIHENLPRFIDNLQILATIKQKHSALYDQIINELTASGLDVSLASHLDGYH 241
|||||| |||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 190 DKHTAIA YRLIHENLPRFIDNLQILATIKQKHSALYDQIINELTASGLDVSLASHLDGYH 249
Qy 242 KLLTQEGITAYNTLLGGISGEAGSRKIQGINELINSHHNQHCHKSERIAKLRPLHKQILS 301
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 250 KLLTQEGITAYNTLLGGISGEAGSRKIQGINELINSHHNQHCHKSERIAKLRPLHKQILS 309
Qy 302 DGMGVSFLPSKFADDSEMCQAVNEFYRHYADVFAKVQSLFDGFDDHQKDGIYVEHKNLNE 361
|||||||||||||||||:|||||||||||||||||||||||||||:||||||||:|||||
Db 310 DGMGVSFLPSKFADDSEVCQAVNEFYRHYADVFAKVQSLFDGFDDYQKDGIYVEYKNLNE 369
Qy 362 LSKQAFGDFALLGRVLDGYYVDVVNPEFNERFAKAKTDNAKAKLTKEKDKFIKGVHSLAS 421
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 370 LSKQAFGDFALLGRVLDGYYVDVVNPEFNERFAKAKTDNAKAKLTKEKDKFIKGVHSLAS 429
Qy 422 LEQAIEHYTARHDDESVQAGKLGQYFKHGLAGVDNPIQKIHNNHSTIKGFLERERPAGER 481
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 430 LEQAIEHYTARHDDESVQAGKLGQYFKHGLAGVDNPIQKIHNNHSTIKGFLERERPAGER 489
Qy 482 ALPKIKSGKNPEMTQLRQLKELLDNALNVAHFAKLLTTKTTLDNQDGNFYGEFGALYDEL 541
||||||| |:|| :|||||||||||||||||||||||||| |||||||||||||||||
Db 490 ALPKIKSDKSPE---IRQLKELLDNALNVAHFAKLLTTKTTLHNQDGNFYGEFGALYDEL 546
Qy 542 AKIPTLYNKVRDYLSQKPFSTEKYKLNFGNPTLLNGWDLNKEKDNFGIILQKDGCYYLAL 601
||| |||||||||||||||||||||||||||||||||||||||||||:||||||||||||
Db 547 AKIATLYNKVRDYLSQKPFSTEKYKLNFGNPTLLNGWDLNKEKDNFGVILQKDGCYYLAL 606
Qy 602 LDKAHKKVFDNAPNTGKNVYQKMIYKLLPGPNKMLPKVFFAKSNLDYYNPSAELLDKYAQ 661
|||||||||||||||||:||||||||||||||||||||||||||||||||||||||||||
Db 607 LDKAHKKVFDNAPNTGKSVYQKMIYKLLPGPNKMLPKVFFAKSNLDYYNPSAELLDKYAQ 666
Qy 662 GTHKKGNNFNLKDCHALIDFFKAGINKHPEWQHFGFKFSPTSSYQDLSDFYREVEPQGYQ 721
||||||:|||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 667 GTHKKGDNFNLKDCHALIDFFKAGINKHPEWQHFGFKFSPTSSYQDLSDFYREVEPQGYQ 726
Qy 722 VKFVDINADYINELVEQGQLYLFQIYNKDFSPKAHGKPNLHTLYFKALFSKDNLANPIYK 781
||||||||||||||||||||||||||||||||||||||||||||||||||:||| |||||
Db 727 VKFVDINADYINELVEQGQLYLFQIYNKDFSPKAHGKPNLHTLYFKALFSEDNLVNPIYK 786
Qy 782 LNGEAQIFYRKASLDMNETTIHRAGEVLENKNPDNPKKRQFVYDIIKDKRYTQDKFMLHV 841
|||||:||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 787 LNGEAEIFYRKASLDMNETTIHRAGEVLENKNPDNPKKRQFVYDIIKDKRYTQDKFMLHV 846
Qy 842 PITMNFGVQGMTIKEFNKKVNQSIQQYDEVNVIGIDRGERHLLYLTVINSKGEILEQRSL 901
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 847 PITMNFGVQGMTIKEFNKKVNQSIQQYDEVNVIGIDRGERHLLYLTVINSKGEILEQRSL 906
Qy 902 NDITTASANGTQMTTPYHKILDKREIERLNARVGWGEIETIKELKSGYLSHVVHQISQLM 961
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 907 NDITTASANGTQMTTPYHKILDKREIERLNARVGWGEIETIKELKSGYLSHVVHQISQLM 966
Qy 962 LKYNAIVVLEDLNFGFKRGRFKVEKQIYQNFENALIKKLNHLVLKDEADDEIGSYKNALQ 1021
||||||||||||||||||||||||||||||||||||||||||||||:|||||||||||||
Db 967 LKYNAIVVLEDLNFGFKRGRFKVEKQIYQNFENALIKKLNHLVLKDKADDEIGSYKNALQ 1026
Qy 1022 LTNNFTDLKSIGKQTGFLFYVPAWNTSKIDPETGFVDLLKPRYENIAQSQAFFGKFDKIC 1081
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1027 LTNNFTDLKSIGKQTGFLFYVPAWNTSKIDPETGFVDLLKPRYENIAQSQAFFGKFDKIC 1086
Qy 1082 YNADKDYFEFHIDYAKFTDKAKNSRQIWKICSHGDKRYVYDKTANQNKGATKGINVNDEL 1141
||||: ||||||||||| ||||||||||||||||||||||||||||||||| |:||||||
Db 1087 YNADRGYFEFHIDYAKFNDKAKNSRQIWKICSHGDKRYVYDKTANQNKGATIGVNVNDEL 1146
Qy 1142 KSLFARHHINDKQPNLVMDICQNNDKEFHKSLIYLLKTLLALRYSNASSDEDFILSPVAN 1201
|||| |:|||||||||||||||||||||||||:|||||||||||||||||||||||||||
Db 1147 KSLFTRYHINDKQPNLVMDICQNNDKEFHKSLMYLLKTLLALRYSNASSDEDFILSPVAN 1206
Qy 1202 DEGMFFNSALADDTQPQNADANGAYHIALKGLWVLEQIKNSDDLNKVKLAIDNQTWLNFA 1261
|||:|||||||||||||||||||||||||||||:| ::||||||||||||||||||||||
Db 1207 DEGVFFNSALADDTQPQNADANGAYHIALKGLWLLNELKNSDDLNKVKLAIDNQTWLNFA 1266
Qy 1262 QNR 1264
|||
Db 1267 QNR 1269
Claim(s) 13 remains rejected under 35 U.S.C. 103 as being unpatentable over Doudna (US10253365 B1), Kleinstiver et al 2019 (Nature Biotechnology 37:3, p.276-282) as applied to claims 1-4, 6, 8-12, 16, 18, and 20-21 above, and further in view of Zhang et al (US 20160208243 A1).
Claim 5 is drawn to the method of claim 1 wherein said modified nucleotide sequence comprises insertion of a polynucleotide that encodes a protein that confers antibiotic or herbicide tolerance.
Doudna and Kleinstiver collectively teach all the limitations of claim 6.
Doudna and Kleinstiver collectively do not teach codon-optimized sequences encoding a Cpf1.
Zhang teaches genome modification to confer antibiotic or herbicide resistance (Paragraphs 1112-1116). Zhang further teaches codon optimized polynucleotides encoding the Cpf1 for eukaryotes including plants (paragraphs 218, 840, 848, and elsewhere).
At the time of filing, it would have been prima facie obvious for a person of ordinary skill in the art to use codon-optimized sequences encoding the Cpf1 to optimize expression of the genome modifying enzyme. Further, a person of ordinary skill would have motivated to combine the cited references to generate an herbicide resistant plant as this would confer an added utility to the plant.
Claim(s) 7 remain rejected under 35 U.S.C. 103 as being unpatentable over Doudna (US10253365 B1), Kleinstiver et al 2019 (Nature Biotechnology 37:3, p.276-282) as applied to claims 1-4, 6, 8-12, 16, 18, and 20-21 above, and further in view of Joung et al (US 20180030425 A1).
Claims 7 is drawn to the composition of claim 6 wherein said Cpf1 compromises a mutation in a position corresponding to positions 877-971 of SEQ ID NO:3.
Doudna and Kleinstiver collectively teach all the limitations of claim 6.
Doudna and Kleinstiver collectively do not teach wherein said Cpf1 compromises a mutation in a position corresponding to positions 877-971 of SEQ ID NO:3.
Joung teaches several variants of Cpf1 nucleases with decreased nuclease activity including having mutations over the claimed region (see claims 3 and 6).
At the time of filing, it would have been prima facie obvious for a person of ordinary skill in the art to make variants of the nuclease collectively taught by Doudna and Kleinstiver to make a non-nuclease fusion protein (such as DNMT1 fusions taught by Joung) for genome modification. As person of ordinary skill in the art would have been motivated to use variants with alter PAM specificity (as taught by Kleinstiver), so that as greater diversity of sites can been targeted. As such, claim 7 is rejected as being obvious.
Response to Arguments - Claim Rejections - 35 USC § 103
Applicant's amendments filed 22 January 2026 been fully considered and partially overcome the rejection (claim 1 and its dependents are no longer rejected over Doudna, but are now rejected over Zhang. Claim 6 and its dependents remain rejected using Doudna as a primary reference. Arguments have been fully considered and responses are below in regard to claims rejected over Doudna.
First, it is noted that claims 14-15, 17, and 19 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims. These are the claims limited to specific Cas12a variants.
Applicant has not taught non-obviousness for the invention as broadly claimed. See In re Lindner, 173 USPQ 356 (CCPA 1972) and In re Grasselli, 218 USPQ 769 (Fed. Cir. 1983) which teach that the evidence of nonobviousness should be commensurate with the scope of the claims. Applicant argues that unexpected results were achieved in the McCpf1 D172R variant. No rejected claims are limited to the embodiment shown to produce the unexpected results. Further, not claims recite any specific level of editing efficiency.
Applicant urges that the Office has not provided a specific reason to select Doudna’s SEQ ID NO:7 and the mutations of Kleinstiver. Applicant cites two more pieces of prior art non-patent literature (Gao et al and Li et al) which teach other sites that could be mutated in a Cpf1 enzyme to alter function of the enzyme.
This argument is not persuasive. First, no rejected claims are limited to specific Cas12a variants. The Office’s position is that it would have been obvious make the mutations of Kleinstiver, Gao, or Li in any Cas12a known in the prior absent evidence to contrary. That being said, Kleinstiver was published in Nature Biotechnology which is a widely read and respected journal. Given that all the rejected claims are still claim a large genus of embodiments, the arguments that are directed toward the specificity of the claims not being address are not persuasive.
Claim(s) 1-5, 11, and 16 is rejected under 35 U.S.C. 103 as being unpatentable over Zhang (US9790490 B2), and further in view of Kleinstiver et al 2019 (Nature Biotechnology 37:3, p.276-282).
Zhang teaches extensive applications of Cpf1 (Cas12a) endonucleases to make targeted genome modifications in plants (columns 207-239, note column 214, 217, 222). SEQ ID NO:100 encodes one of the Cpf1 polypeptides identified by which is identical to instant SEQ ID NO:10 but for the single base substitution at position 174 (see alignment below).
Zhang et al do not teach any of the specific mutations recited in claim 1.
Kleinstiver et al teach engineering of Cas12a (synonymous with Cpf1) variants to alter PAM specificity by mutating E174R/S542R/K548R. Instant SEQ ID NO:10 also comprises an E at position 174.
At the time of filing, it would have been prima facie obvious for a person of ordinary skill in the art to substitute E174R in Cpf1 of SEQ ID NO:100 of Zhang to the end of altering PAM specificity of the Cpf1 of Zhang. In combining these teachings, the resultant Cpf1 would comprise a E174R substitution and be 100% identical to SEQ ID NO:10. It further would have been obvious to carry out the modification at a temperature of less than 32 C because most field crops have ideal growth temperatures at less than 32 C. Accordingly, claims 1-5, 11, and 16 is/are rejected under 35 U.S.C. 103 as being unpatentable over Zhang and further in view of Kleinstiver et al.
US-14-975-085A-100
(NOTE: this sequence has 11 duplicates in the database searched.
See complete list at the end of this report)
Sequence 100, US/14975085A
Patent No. 9790490
GENERAL INFORMATION
APPLICANT: ZHANG, FENG
APPLICANT: ZETSCHE, BERND
APPLICANT: SLAYMAKER, IAN
APPLICANT: GOOTENBERG, JONATHAN S.
APPLICANT: ABUDAYYEH, OMAR O.
TITLE OF INVENTION: NOVEL CRISPR ENZYMES AND SYSTEMS
FILE REFERENCE: 47627.05.2123
CURRENT APPLICATION NUMBER: US/14/975,085A
CURRENT FILING DATE: 2015-12-18
PRIOR APPLICATION NUMBER: 62/232,067
PRIOR FILING DATE: 2015-09-24
PRIOR APPLICATION NUMBER: 62/205,733
PRIOR FILING DATE: 2015-08-16
PRIOR APPLICATION NUMBER: 62/201,542
PRIOR FILING DATE: 2015-08-05
PRIOR APPLICATION NUMBER: 62/193,507
PRIOR FILING DATE: 2015-07-16
PRIOR APPLICATION NUMBER: 62/181,739
PRIOR FILING DATE: 2015-06-18
NUMBER OF SEQ ID NOS: 1595
SEQ ID NO 100
LENGTH: 1247
TYPE: PRT
ORGANISM: Prevotella bryantii
Query Match 99.2%; Score 6535; Length 1247;
Best Local Similarity 99.9%;
Matches 1246; Conservative 0; Mismatches 1; Indels 0; Gaps 0;
Qy 11 MKFTDFTGLYSLSKTLRFELKPIGKTLENIKKAGLLEQDQHRADSYKKVKKIIDEYHKAF 70
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MKFTDFTGLYSLSKTLRFELKPIGKTLENIKKAGLLEQDQHRADSYKKVKKIIDEYHKAF 60
Qy 71 IEKSLSNFELKYQSEDKLDSLEEYLMYYSMKRIEKTEKDKFAKIQDNLRKQIADHLKGDE 130
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 IEKSLSNFELKYQSEDKLDSLEEYLMYYSMKRIEKTEKDKFAKIQDNLRKQIADHLKGDE 120
Qy 131 SYKTIFSKDLIRKNLPDFVKSDEERTLIKEFKDFTTYFKGFYRNRENMYSAEDKSTAISH 190
|||||||||||||||||||||||||||||||||||||||||| |||||||||||||||||
Db 121 SYKTIFSKDLIRKNLPDFVKSDEERTLIKEFKDFTTYFKGFYENRENMYSAEDKSTAISH 180
Qy 191 RIIHENLPKFVDNINAFSKIILIPELREKLNQIYQDFEEYLNVESIDEIFHLDYFSMVMT 250
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 RIIHENLPKFVDNINAFSKIILIPELREKLNQIYQDFEEYLNVESIDEIFHLDYFSMVMT 240
Qy 251 QKQIEVYNAIIGGKSTNDKKIQGLNEYINLYNQKHKDCKLPKLKLLFKQILSDRIAISWL 310
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 QKQIEVYNAIIGGKSTNDKKIQGLNEYINLYNQKHKDCKLPKLKLLFKQILSDRIAISWL 300
Qy 311 PDNFKDDQEALDSIDTCYKNLLNDGNVLGEGNLKLLLENIDTYNLKGIFIRNDLQLTDIS 370
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 PDNFKDDQEALDSIDTCYKNLLNDGNVLGEGNLKLLLENIDTYNLKGIFIRNDLQLTDIS 360
Qy 371 QKMYASWNVIQDAVILDLKKQVSRKKKESAEDYNDRLKKLYTSQESFSIQYLNDCLRAYG 430
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 QKMYASWNVIQDAVILDLKKQVSRKKKESAEDYNDRLKKLYTSQESFSIQYLNDCLRAYG 420
Qy 431 KTENIQDYFAKLGAVNNEHEQTINLFAQVRNAYTSVQAILTTPYPENANLAQDKETVALI 490
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 KTENIQDYFAKLGAVNNEHEQTINLFAQVRNAYTSVQAILTTPYPENANLAQDKETVALI 480
Qy 491 KNLLDSLKRLQRFIKPLLGKGDESDKDERFYGDFTPLWETLNQITPLYNMVRNYMTRKPY 550
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 KNLLDSLKRLQRFIKPLLGKGDESDKDERFYGDFTPLWETLNQITPLYNMVRNYMTRKPY 540
Qy 551 SQEKIKLNFENSTLLGGWDLNKEHDNTAIILRKNGLYYLAIMKKSANKIFDKDKLDNSGD 610
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 SQEKIKLNFENSTLLGGWDLNKEHDNTAIILRKNGLYYLAIMKKSANKIFDKDKLDNSGD 600
Qy 611 CYEKMVYKLLPGANKMLPKVFFSKSRIDEFKPSENIIENYKKGTHKKGANFNLADCHNLI 670
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 601 CYEKMVYKLLPGANKMLPKVFFSKSRIDEFKPSENIIENYKKGTHKKGANFNLADCHNLI 660
Qy 671 DFFKSSISKHEDWSKFNFHFSDTSSYEDLSDFYREVEQQGYSISFCDVSVEYINKMVEKG 730
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 661 DFFKSSISKHEDWSKFNFHFSDTSSYEDLSDFYREVEQQGYSISFCDVSVEYINKMVEKG 720
Qy 731 DLYLFQIYNKDFSEFSKGTPNMHTLYWNSLFSKENLNNIIYKLNGQAEIFFRKKSLNYKR 790
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 721 DLYLFQIYNKDFSEFSKGTPNMHTLYWNSLFSKENLNNIIYKLNGQAEIFFRKKSLNYKR 780
Qy 791 PTHPAHQAIKNKNKCNEKKESIFDYDLVKDKRYTVDKFQFHVPITMNFKSTGNTNINQQV 850
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 781 PTHPAHQAIKNKNKCNEKKESIFDYDLVKDKRYTVDKFQFHVPITMNFKSTGNTNINQQV 840
Qy 851 IDYLRTEDDTHIIGIDRGERHLLYLVVIDSHGKIVEQFTLNEIVNEYGGNIYRTNYHDLL 910
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 841 IDYLRTEDDTHIIGIDRGERHLLYLVVIDSHGKIVEQFTLNEIVNEYGGNIYRTNYHDLL 900
Qy 911 DTREQNREKARESWQTIENIKELKEGYISQVIHKITDLMQKYHAVVVLEDLNMGFMRGRQ 970
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 901 DTREQNREKARESWQTIENIKELKEGYISQVIHKITDLMQKYHAVVVLEDLNMGFMRGRQ 960
Qy 971 KVEKQVYQKFEEMLINKLNYLVNKKADQNSAGGLLHAYQLTSKFESFQKLGKQSGFLFYI 1030
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 961 KVEKQVYQKFEEMLINKLNYLVNKKADQNSAGGLLHAYQLTSKFESFQKLGKQSGFLFYI 1020
Qy 1031 PAWNTSKIDPVTGFVNLFDTRYESIDKAKAFFGKFDSIRYNADKDWFEFAFDYNNFTTKA 1090
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1021 PAWNTSKIDPVTGFVNLFDTRYESIDKAKAFFGKFDSIRYNADKDWFEFAFDYNNFTTKA 1080
Qy 1091 EGTRTNWTICTYGSRIRTFRNQAKNSQWDNEEIDLTKAYKAFFAKHGINIYDNIKEAIA M 1150
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1081 EGTRTNWTICTYGSRIRTFRNQAKNSQWDNEEIDLTKAYKAFFAKHGINIYDNIKEAIA M 1140
Qy 1151 ETEKSFFEDLLHLLKLTLQMRNSITGTTTDYLISPVHDSKGNFYDSRICDNSLPANADAN 1210
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1141 ETEKSFFEDLLHLLKLTLQMRNSITGTTTDYLISPVHDSKGNFYDSRICDNSLPANADAN 1200
Qy 1211 GAYNIARKGLMLIQQIKDSTSSNRFKFSPITNKDWLIFAQEKPYLND 1257
|||||||||||||||||||||||||||||||||||||||||||||||
Db 1201 GAYNIARKGLMLIQQIKDSTSSNRFKFSPITNKDWLIFAQEKPYLND 1247
Claim Objections
Claims 14-15, 17, and 19 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Conclusion
No claims are allowed. Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MATTHEW R KEOGH whose telephone number is (571)272-2960. The examiner can normally be reached M-Th 7-4:30, half day on Fridays.
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, Amjad Abraham can be reached on 571-270-7058. 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.
/MATTHEW R KEOGH/Primary Examiner, Art Unit 1663