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 .
Election/Restrictions
Applicant's election with traverse of group V, claim 21, and the species SEQ ID NO: 71, in the reply filed on February 4, 2026 is acknowledged. Claim 1 links inventions I-III, V-XI and XV.
The traversal is on the ground(s) that the Office has provided no explanation as to why claim 1 is indicated as non-allowable.
This is not found persuasive because the outstanding restriction requirement does not assert that claim 1 is non-allowable. The outstanding restriction requirement asserts that the restriction requirement among the linked inventions is subject to the nonallowance of the linking claim(s), claim 1, and that upon the indication of allowability of the linking claim(s), the restriction requirement as to the linked inventions shall be withdrawn and any claim(s) depending from or otherwise requiring all the limitations of the allowable linking claim(s) will be rejoined and fully examined for patentability in accordance with 37 CFR 1.104. See MPEP 809.
The traversal is on also the ground(s) that since all the inventions of Groups I-X and XV share a technical feature of the non-naturally occurring CRISPR-Cas system, their restriction is improper.
This is not found persuasive because the instant application was not filed under 37 USC 371. According, the restriction requirement is not predicated on unity of invention standards.
The requirement is still deemed proper and is therefore made FINAL.
Claims 2, 5-6, 8, 26-27, 31, 35, 42, 44, 46, 70, 128, 157, 160-161 and 171-172 are withdrawn.
Improper Markush Grouping
Claim 21 is rejected on the judicially-created basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). The improper Markush grouping includes species of the claimed invention that do not share both a substantial structural feature and a common use that flows from the substantial structural feature. The members of the improper Markush grouping do not share a substantial feature and/or a common use that flows from the substantial structural feature for the following reasons: Claim 21 is drawn to the CRISPR-Cas system of claim 1, wherein the stiCas9 comprises a domain having at least 95% identity to any one of SEQ ID Nos: 10-97 or 192-195. Cas9 proteins are known to be composed of multiple domains that differ in both structure and function. See, e.g., Chylinski et al. Classification and evolution of type II CRISPR-Cas systems. Nucleic Acids Res. 2014 Apr 11;42(10):6091–6105. There is nothing of record to indicate that domains corresponding to SEQ ID Nos: 10-97 or 192-195 all share a substantial structural feature as well as a common use that flows from the substantial structural feature. In response to this rejection, Applicant should either amend the claim(s) to recite only individual species or grouping of species that share a substantial structural feature as well as a common use that flows from the substantial structural feature, or present a sufficient showing that the species recited in the alternative of the claims(s) in fact share a substantial structural feature as well as a common use that flows from the substantial structural feature. This is a rejection on the merits and may be appealed to the Board of Patent Appeals and Interferences in accordance with 35 U.S.C. §134 and 37 CFR 41.31(a)(1) (emphasis provided).
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 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.
Claim(s) 1 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Bassett et al. Highly efficient targeted mutagenesis of Drosophila with the CRISPR/Cas9 system. Cell Rep. 2013 Jul 11;4(1):220-8. Epub 2013 Jul 1.
Claim 1 is drawn to a non-naturally occurring CRISPR-Cas system comprising:
a) a Cas9 effector protein capable of generating cohesive ends (stiCas9); and
b) a guide polynucleotide that forms a complex with the stiCas9 and comprises a guide sequence, wherein the guide sequence is capable of hybridizing with a target sequence in a eukaryotic cell but does not hybridize to a sequence in a bacterial cell; wherein the complex does not occur in nature.
Bassett et al. teach a Streptococcus pyrogenes Cas9 effector protein and a guide polynucleotide that forms a complex with the Cas9 (page 220 column 2 first full paragraph). The Streptococcus pyrogenes Cas9 effector protein is inherently capable of generating staggered (cohesive) ends as evidenced by Zuo et al. Cas9-catalyzed DNA Cleavage Generates Staggered Ends: Evidence from Molecular Dynamics Simulations. Sci. Rep. 2016 Nov 22;5:37584. The guide sequence is capable of hybridizing with a target sequence in a eukaryotic cell but does not hybridize to a sequence in a bacterial cell because the guide sequence is engineered to specifically hybridize to a Drosophila gene. The Cas9/guide polynucleotide complex is non-naturally occurring (does not occur in nature) because it is produced in vitro. Bassett et al. also teach that the Streptococcus pyrogenes Cas9 effector protein is guided to its target site by complementary base pairing of CRISPR RNAs (crRNAs) with the target DNA sequence, and requires a third component, the tracrRNA, which recruits the crRNA into the Cas9 complex (page 220 paragraph spanning columns 1 and 2), and that they have modified a two component system in which the crRNA and the tracrRNA are fused into a single synthetic guide RNA to create targeted mutations in the Drosophila yellow and white genes (page 220 column 2 first full paragraph). Accordingly, Bassett et al. anticipate claim 1.
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.
Claim(s) 1 and 21 is/are rejected under 35 U.S.C. 103 as being unpatentable over Doudna et al. U.S. Patent Application No. 2014/0068797, published Mar. 6, 2014.
Claim 1 is drawn to a non-naturally occurring CRISPR-Cas system comprising:
a) a Cas9 effector protein capable of generating cohesive ends (stiCas9); and
b) a guide polynucleotide that forms a complex with the stiCas9 and comprises a guide sequence, wherein the guide sequence is capable of hybridizing with a target sequence in a eukaryotic cell but does not hybridize to a sequence in a bacterial cell; wherein the complex does not occur in nature.
Claim 21 is drawn to the CRISPR-Cas system of claim 1, wherein the stiCas9 comprises a domain having at least 95% identity to any one of SEQ ID Nos: 10-97 or 192-195.
Doudna et al. teach a Cas9 effector protein obtained from Francisella cf. novicida 3523 that has at least 95% identity to SEQ ID NO: 194 – see the sequence alignment below between SEQ ID NO:194 and SEQ ID NO: 962 of Doudna et al. Cas9 effector proteins are known to be capable of generating cohesive ends as evidenced by Zuo et al. Cas9-catalyzed DNA Cleavage Generates Staggered Ends: Evidence from Molecular Dynamics Simulations. Sci. Rep. 2016 Nov 22;5:37584. Doudna et al. teach that a DNA-targeting RNA (i.e. a guide polynucleotide) that comprises a targeting sequence can form a complex with a Cas9 effector protein and can be used to provide for site-specific modification of a target DNA, including a target DNA in a eukaryotic cell (in which case the guide sequence would not hybridize to a sequence in a bacterial cell and the complex would not occur in nature because the target is eukaryotic rather than prokaryotic) (paragraphs [0017], [0135]).
Doudna et al. do not teach a specific embodiment exemplifying a complex comprising the Cas9 effector protein obtained from Francisella cf. novicida 3523 that has at least 95% identity to SEQ ID NO: 194 and a guide polynucleotide.
Given the teachings of Doudna et al. that a Cas9 effector protein, including a Cas9 effector protein obtained from Francisella cf. novicida 3523 that has at least 95% identity to SEQ ID NO: 194, can be used with a DNA-targeting RNA (i.e. a guide polynucleotide) that comprises a targeting sequence that forms a complex with a Cas9 effector protein to provide for site-specific modification of a target DNA, including a target DNA in a eukaryotic cell, it would have been prima facie obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to make a non-naturally occurring CRISPR-Cas system comprising a Cas9 effector protein obtained from Francisella cf. novicida 3523 that has at least 95% identity to SEQ ID NO: 194 and a guide polynucleotide that comprises a guide sequence capable of hybridizing with a target sequence in a eukaryotic cell
One skilled in the art could readily combine prior art elements such as a Cas9 effector protein obtained from Francisella cf. novicida 3523 that has at least 95% identity to SEQ ID NO: 194 and a DNA-targeting RNA (i.e. a guide polynucleotide) that comprises a targeting sequence that forms a complex with a Cas9 effector protein to yield predictable results, i.e. site-specific modification of a target DNA, since the elements were already known in the art to be useful for this purpose.
Thus, the claimed invention would have been prima facie obvious as a whole to a person having ordinary skill in the art before the effective filing date of the claimed invention.
Sequence alignment between SEQ ID NO:194 and SEQ ID NO: 962 of Doudna et al.:
RESULT 2
US-13-842-859A-962
(NOTE: this sequence has 212 duplicates in the database searched.
See complete list at the end of this report)
Sequence 962, US/13842859A
Publication No. US20140068797A1
GENERAL INFORMATION
APPLICANT: Jinek, Martin
APPLICANT: Doudna, Jennifer A.
APPLICANT: Charpentier, Emmanuelle
APPLICANT: Chylinski, Krzysztof
APPLICANT: Doudna Cate, James H.
APPLICANT: Lim, Wendell
APPLICANT: Qi, Lei
TITLE OF INVENTION: METHODS AND COMPOSITIONS FOR RNA-DIRECTED TARGET DNA MODIFICATION
TITLE OF INVENTION: AND FOR RNA-DIRECTED MODULATION OF TRANSCRIPTION
FILE REFERENCE: BERK-187
CURRENT APPLICATION NUMBER: US/13/842,859A
CURRENT FILING DATE: 2013-03-15
PRIOR APPLICATION NUMBER: US 61/652,086
PRIOR FILING DATE: 2012-05-25
PRIOR APPLICATION NUMBER: US 61/716,256
PRIOR FILING DATE: 2012-10-19
PRIOR APPLICATION NUMBER: US 61/757,640
PRIOR FILING DATE: 2013-01-28
PRIOR APPLICATION NUMBER: US 61/765,576
PRIOR FILING DATE: 2013-02-15
NUMBER OF SEQ ID NOS: 1360
SEQ ID NO 962
LENGTH: 1646
TYPE: PRT
ORGANISM: Unknown
FEATURE:
OTHER INFORMATION: Francisella cf. novicida 3523
Query Match 97.3%; Score 8328.5; Length 1646;
Best Local Similarity 96.9%;
Matches 1595; Conservative 22; Mismatches 22; Indels 7; Gaps 2;
Qy 1 MNIKILPIAIDLGAKNTGVFSAFYQKGTSLESLDNKNGKVYELSKDSYTLLMNNRTARRH 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MNIKILPIAIDLGAKNTGVFSAFYQKGTSLESLDNKNGKVYELSKDSYTLLMNNRTARRH 60
Qy 61 QRRGIDRKQLVKRLFKLIWTKQLNLEWNKDTQQTISFLLNRRGFSFITDGYSPEYLNIAP 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 QRRGIDRKQLVKRLFKLIWTKQLNLEWNKDTQQTISFLLNRRGFSFITDGYSPEYLNIAP 120
Qy 121 EPVKVILMSILDDYNGEDDLDSYLQSATENDSKIDELYNKLLQKTLEFKLRKLCIDIKED 180
| || ||||||||||||||||||||||||||||||||||||||| |||||||||||||||
Db 121 EAVKAILMSILDDYNGEDDLDSYLQSATENDSKIDELYNKLLQKALEFKLRKLCIDIKED 180
Qy 181 KVTTKTLKELSNTEFKLLANYLVDYDRILRTQKFSYTDKQGNLRELNYYHHDKYNIQEFL 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 KVTTKTLKELSNTEFKLLANYLVDYDRILRTQKFSYTDKQGNLRELNYYHHDKYNIQEFL 240
Qy 241 KRNIIINDVILEKLTDDLDIWNLNFDKFDFEKNLEKLENQEDKDYLQTHLHHFVFAVNKI 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 KRNIIINDVILEKLTDDLDIWNLNFDKFDFEKNLEKLENQEDKDYLQTHLHHFVFAVNKI 300
Qy 301 KSEMASGGRHRSQYFQEITNVLVENNHQEGYLKNFCENLHNKKYSNLSVKNLVNLIGNLS 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 KSEMASGGRHRSQYFQEITNVLVENNHQEGYLKNFCENLHNKKYSNLSVKNLVNLIGNLS 360
Qy 361 NLELKPLRKYFNDKIHAKADYWDEQKFAETYSDWILGEWRVGAKDKDKKDGAKYSYKILC 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||| ||
Db 361 NLELKPLRKYFNDKIHAKADYWDEQKFAETYSDWILGEWRVGAKDKDKKDGAKYSYKNLC 420
Qy 421 DELKQKVGINQDGIINQTKGDFVGFLLELDPCRTIPPYLDNNNRKPPKCQSLILNPKFLD 480
||||||||||||||||||| ||| ||||||||||||||||||||||||||||||||||||
Db 421 DELKQKVGINQDGIINQTKSDFVDFLLELDPCRTIPPYLDNNNRKPPKCQSLILNPKFLD 480
Qy 481 NKYPNWQQYLQELKKLQTVQNYLGNFEIDLKDLKSSKEQPYFVKYKSSNQQIASGQRDYK 540
||||||||||||||||||||||||||||||||||||||||||||||| ||||||||||||
Db 481 NKYPNWQQYLQELKKLQTVQNYLGNFEIDLKDLKSSKEQPYFVKYKSLNQQIASGQRDYK 540
Qy 541 DLDARVLQFIFDRVKASDELLLNEIYSHAKKLKQNISSELEKLELCKKLDKIIANSQLSQ 600
||||||||||||||||||||||||||||||||||| ||||||||||||||::||||||||
Db 541 DLDARVLQFIFDRVKASDELLLNEIYSHAKKLKQNTSSELEKLELCKKLDEVIANSQLSQ 600
Qy 601 ILKSQHINGIFEQGTFLHLVCKYYKQRQRARDSRLYIMPEYRYDKKLDKYNNTGRFDDDN 660
||||||:|||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 601 ILKSQHVNGIFEQGTFLHLVCKYYKQRQRARDSRLYIMPEYRYDKKLDKYNNTGRFDDDN 660
Qy 661 QLLTYCNHKPRQKRYQLLNDLAGVLQVSPNFLKDKIGSDDDLFISKWLVEHIRGFKKACE 720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 661 QLLTYCNHKPRQKRYQLLNDLAGVLQVSPNFLKDKIGSDDDLFISKWLVEHIRGFKKACE 720
Qy 721 DSLKIQKDNRGLLNHKINIARNTKGKCEKEIFNLICKIEGSEDKKGNYKHGLAYELGVLL 780
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 721 DSLKIQKDNRGLLNHKINIARNTKGKCEKEIFNLICKIEGSEDKKGNYKHGLAYELGVLL 780
Qy 781 FGEPNQASKLEFDRKIKKFNSIYSFAQIQQIAFAERKGNANTCAVCSADNAHRMQQIKVA 840
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 781 FGEPNQASKLEFDRKIKKFNSIYSFAQIQQIAFAERKGNANTCAVCSADNAHRMQQIKVA 840
Qy 841 KPVEGNKDNIILSAKAQRLPAIPTRIVDGAVKKMATILARNIVDDNWDNIKQALSNNQQL 900
|||||||||||||||||||||||||||||||||:||||||||||||||||||||||||||
Db 841 KPVEGNKDNIILSAKAQRLPAIPTRIVDGAVKKIATILARNIVDDNWDNIKQALSNNQQL 900
Qy 901 HVPIITESNAFEFEPALADVKGKSLKDKRKKALERINPENTFKDKNNRIKEFAKGISAYS 960
|||||||||||||||||||:||||||||||||||||:||| |||||||||||||||||||
Db 901 HVPIITESNAFEFEPALADIKGKSLKDKRKKALERIDPENVFKDKNNRIKEFAKGISAYS 960
Qy 961 GDNLANGDFDGAKEELDHIIPRAHKKYGTLNDEANLICVTREDNQNRGNKAVFLYDLKPN 1020
||||||||||||||||||||:|||||||||||||||||||||||||||||||||||||
Db 961 DANLANGDFDGAKEELDHIIPRSHKKYGTLNDEANLICVTREDNQNRGNKAVFLYDLKPN 1020
Qy 1021 YKLKQFDTTDDLEIEKKIADTIWDASKQDFKFGNYRSFINLTPQEQKAFRHALFLADENP 1080
||||||:||||||||||||||||||||||||||||||||||||||| ||||||||||:||
Db 1021 YKLKQFNTTDDLEIEKKIADTIWDASKQDFKFGNYRSFINLTPQEQIAFRHALFLADKNP 1080
Qy 1081 IKKAVIRAINNRNRTFVNGTQRYFAEVLANNIYLRAKKENLATNRITFDYFGIETTNSNG 1140
|||||||||:||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1081 IKKAVIRAIDNRNRTFVNGTQRYFAEVLANNIYLRAKKENLATNRITFDYFGIETTNSNG 1140
Qy 1141 RGVADVRKLYEKVDSDIQAYAKGDKPQDSYSHLIDAMIAFCVAADEHKNGGSIGLEIDKN 1200
||:|||||||||||||||||||||||||||||||||||||||||||||| |||||::
Db 1141 RGIADVRKLYEKVDSDIQAYAKGDKPQDSYSHLIDAMIAFCVAADEHKNEGSIGLKMGNQ 1200
Qy 1201 YSLYP----LDKNTGEVFS---KDIFSQIKIADNEFSDKKLVRKKATEGFNTHRQMTRDG 1253
| |:| |:||||: | ||| :||::||:|||||||||||||||||||||||||
Db 1201 YGLFPTPDKYDENTGEIISWHNDDIFRKIKVSDNQFSDKKLVRKKATEGFNTHRQMTRDG 1260
Qy 1254 IYGESYLPILIHKNLNEVRKGYNWENSEEIKIFKGKKYDIQQLNNLVYCLKFVDKPISID 1313
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1261 IYGESYLPILIHKNLNEVRKGYNWENSEEIKIFKGKKYDIQQLNNLVYCLKFVDKPISID 1320
Qy 1314 IQITTLEELRNILETNNISTTAEYYYINLKTQKLHEYYIENYNTALGYKKYTKEMEFLRS 1373
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1321 IQITTLEELRNILETNNISTTAEYYYINLKTQKLHEYYIENYNTALGYKKYTKEMEFLRS 1380
Qy 1374 LAYRTERVKIKSIDDVSMILAKDSNFKAGKIELPFKTEWQRLYLEWQNTTIKDNYEFLKS 1433
||||||||||||||||||||||||||||||||||||||||||||||||||||||:|||||
Db 1381 LAYRTERVKIKSIDDVSMILAKDSNFKAGKIELPFKTEWQRLYLEWQNTTIKDNHEFLKS 1440
Qy 1434 YFSVKNATKQHKKVRKDFSLPISTNEGKLLVKRKTWDNNFIYQILNDSDSRADGTKPFIP 1493
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1441 YFSVKNATKQHKKVRKDFSLPISTNEGKLLVKRKTWDNNFIYQILNDSDSRADGTKPFIP 1500
Qy 1494 AFDISKNEIVETIIKSFTSKNIFWLPKNIKLQKVDNKSIFAIDTSRWFEVETPKDLIEIG 1553
|||||||||||||||||||||||||||||:||||||||||||||||||||||||||||||
Db 1501 AFDISKNEIVETIIKSFTSKNIFWLPKNIELQKVDNKSIFAIDTSRWFEVETPKDLIEIG 1560
Qy 1554 VSTIQYKIDNNSRPKVRVKLDYVMDDDSKINYFMNHSLLKSRYPDKVLEILKQSTIIEFE 1613
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1561 VSTIQYKIDNNSRPKVRVKLDYVMDDDSKINYFMNHSLLKSRYPDKVLEILKQSTIIEFE 1620
Qy 1614 SSGFNKTIKEMLGMTLAGIYNETLNN 1639
||||||||||||||||||||||| ||
Db 1621 SSGFNKTIKEMLGMTLAGIYNETSNN 1646
Remarks
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CYNTHIA E COLLINS whose telephone number is (571)272-0794. The examiner can normally be reached M-F 8:30 am - 5:00 pm.
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, Bratislav Stankovic can be reached at 571-270-0305. 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.
/CYNTHIA E COLLINS/Primary Examiner, Art Unit 1662
Prosecution Insights