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 .
Examiner’s Note/Status of the Claims
The last amendment filed on 01/24/2025, in which claims 1, 15-6, 24-25, and 27 were amended, claims 2-3, 6, and 19-22 were cancelled and no new claims were added, is acknowledged and entered.
Election/Restrictions
The applicant’s election of species without traverse in the reply filed on 01/24/2025 is acknowledged.
Applicant election without traverse of species that includes: a) A guide ribonucleic acid sequence complementary to a eukaryotic genomic sequence;
b) An NLS sequence of SEQ ID NO: 5597;
Claims encompassing the elected species include claims 1, 4, 5, 7-18, and 23-27.
Information Disclosure Statement
The information disclosure statement filed on 11/27/2024 has been considered.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code as recited in [00193]. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency - Sequences appearing in the drawings are not identified by sequence identifiers in accordance with 37 CFR 1.831(c). The SEQ ID NOS: of the sequences drawn in Figures 9A-H are not properly indicated in specifications or the order of the SEQ ID NOS: for the respective sequences are not clear. The SEQ ID NOS: for the sequences drawn in Figures 21-33 are not present in the drawings or in the specifications. Sequence identifiers for sequences (i.e., “SEQ ID NO:X” or the like) must appear either in the drawings or in the Brief Description of the Drawings.
Required response – Applicant must provide:
Amended drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers;
AND/OR
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required sequence identifiers (i.e., “SEQ ID NO:X” or the like) into the Brief Description of the Drawings, consisting of:
• A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
• A copy of the amended specification without markings (clean version); and
• A statement that the substitute specification contains no new matter.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1, 4-5, 7-9, 12-18, and 23-27 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a product of nature without significantly more.
Regarding claim 1, the claim is drawn to “an engineered nuclease system, comprising:(a) an endonuclease […], wherein the said endonuclease is a type II Cas endonuclease; and (b) an engineered guide ribonucleic acid […] bind to said endonuclease”. As per MPEP 2106.04(c), since the claim requires a product of nature, the pertinent analysis that will be applied to the claim is the markedly different analysis.
The appropriate counterparts to the currently claimed product of nature are as follows: 1) an endonuclease to have selectivity for a PAM wherein the naturally occurring endonuclease to have selectivity for a protospacer adjacent motif (PAM) wherein the naturally occurring endonuclease system comprises a RuvC_III domain with a sequence having identity at least 80% sequence identity to SEQ ID NO: 3331, wherein the naturally occurring endonuclease is a class 2, type II Cas endonuclease and 2) a naturally occurring guide ribonucleic acid (guide RNA) structure configured to form a complex with the endonuclease comprising: (i) a naturally occurring guide RNA sequence configured to hybridize to a target deoxyribonucleic acid sequence; and (ii) a naturally occurring tracr ribonucleic acid sequence configured to bind to said endonuclease.
The appropriate characteristics identified for analysis are the physical structures of “the endonuclease comprises a RuvC_III domain with a sequence having identity at least 80% sequence identity to SEQ ID NO: 3331 and wherein the endonuclease is a class 2, type II Cas endonuclease.” Furthermore, another appropriate characteristic identified for analysis include biological functions of “an endonuclease to have selectivity for a PAM (SEQ ID NO: 5524); a guide RNA structure configured to form a complex with the endonuclease comprising a guide RNA sequence configured to hybridize to a target DNA sequence; and a tracr RNA sequence configured to bind to the endonuclease.”
The term “engineered” is not interpreted as appropriate characteristics to be identified for analysis because these limitations do not affect the structure nor function of the endonuclease system. The term “engineered” also broadly refers to and reasonably interprets as the process of "genetic engineering" which does not require a markedly different structural or functional characteristic. The instant specification discloses that an “engineered” object can indicate a modified object in general, such as modified nucleic acid by changing sequence or ligating to a nucleic acid to possess a new functional characteristic; or an engineered nucleic acid may be synthesized in vitro and so on ([00189]). But the instant specification does not specify any engineered process that would markedly change the structural or functional characteristics of the claimed naturally occurring products. Therefore, the term engineered does not impose a markedly different structural or functional characteristic on the claimed endonuclease system.
Regarding the physical structure of the endonuclease comprising a RuvC_III domain with a sequence having identity at least 80% sequence identity to SEQ ID NO: 3331 and wherein the endonuclease is a class 2, type II Cas endonuclease, the instant specification teaches that the endonuclease is derived from an uncultivated microorganism, and a nucleic acid sequence optimized for expression in an organism encodes a class 2 type II endonuclease comprising a RuvC_III domain and an HNH domain ([0035]). In this regard the instant specification discloses that the naturally occurring MG1 family of CRISPR systems comprises HNH and RuvC domains including RuvC_III ([00370]. The instant specification also teaches that a vector comprising a nucleic acid sequence encoding a class 2, type II Cas endonuclease comprising a RuvC_III domain and an HNH domain, wherein the endonuclease is derived from an uncultivated microorganism ([0038]). Given the broadest reasonable interpretation of the claim limitation and in view of the instant specification, “derived from an uncultivated microorganism” is interpreted as not grown in the laboratory or simply naturally occurring and “a nucleic acid sequence optimized for expression in an organism encoding a class 2 type II endonuclease comprising a RuvC_III domain and an HNH domain” is interpreted as merely a routine experimentation without markedly changing the structural characteristic of the naturally occurring product. The instant specification also discloses that the full-length peptide sequences of RuvC_III and HNH domains are derived from MG nuclease family (a naturally occurring product) or MG1 in this case ([0077-0080]) and the SEQ ID NO: 3331 comprising the full-length sequences of RuvC_III domain is derived from MG21 nuclease ([00151]) and is merely identified by metagenomic analysis without altering the RuvC_III structure ([00369]). Thus, the instant specification indicates that the endonuclease comprising a RuvC_III domain with a sequence having identity at least 80% sequence identity to SEQ ID NO: 3331 and wherein the endonuclease is a class 2, type II Cas endonuclease, is naturally occurring or derived from a naturally occurring endonuclease.
Regarding the biological functions of an endonuclease to have selectivity for a PAM, particularly in view of the instant specification, the claimed limitation does not possess a markedly different biological function when compared to a naturally occurring endonuclease. The instant specification teaches that in order to determine the target specificity of the MG21 family endonuclease (comprising the full-length peptide sequence of RuvC_III domain as discussed above) is screened for a PAM sequence from a randomly generated putative PAM sequences in an E. Coli expression system ([00466]). Regarding the PAM SEQ ID NO: 5524, the instant specification teaches that the specificity of the PAM sequence is identified for the naturally occurring enzyme ([00377]). Furthermore regarding the PAM identification and specificity for type II nuclease, Gleditzsch (RNA Biol. 2018 Sep 18;16(4):504–517) teaches that the PAM specificity of naturally occurring Cas9 orthologues provides means for broadening the target range of these nucleases (pg. 509, column 2, paragraph 2). Gleditzsch also teaches that efficient PAM binding or detecting target sequences depends on naturally occurring nuclease domains or structural conformation of the nuclease domain, a characteristic of different targeting mechanisms of Cas proteins utilized in the proper protection of the host genome (pg. 504, paragraph 1). Thus the teachings of the instant specification and Gleditzsch indicate that the biological function that confers the PAM specificity of the naturally occurring endonuclease is not modified to create any markedly different functional characteristics or the process is not different from a naturally evolved mechanism.
Regarding the biological functions of “a guide RNA structure configured to form a complex with the endonuclease comprising a guide RNA sequence configured to hybridize to a target DNA sequence; and a tracr RNA sequence configured to bind to the endonuclease”, particularly in view of the instant specification, the claimed limitation does not possess a markedly different biological function when compared to a naturally occurring CRISPR/Cas nuclease system. Given the broadest reasonable interpretation of the claim, the claim limitation is interpreted as requiring that the guide RNA endonuclease complex comprises the guide RNA that binds a target DNA and the tracrRNA that binds the endonuclease and wherein the guide RNA forms a complex with the endonuclease comprising a RuvC_III domain. The instant specification teaches that naturally occurring sgRNA comprises a 5' sequence beginning with G followed by 20 nt of a complementary targeting nucleic acid sequence targeting genomic DNA followed by a corresponding compatible PAM identified (such as the PAM specificity is identified for a naturally occurring enzyme, as described above) and a 3' tracr-binding sequence, a linker, and the tracrRNA sequence ([00380]) . The instant specification also discloses that the nucleotide sequence of MG21 tracrRNA (comprising the SEQ ID NO: 5509) is derived from the same loci as MG21 nuclease (comprising the RuvC_III domain sequence, as discussed above) ([00153]). Thus the instant specification teaches an nuclease system comprising the claimed biological function that does not possess any markedly different characteristics from the naturally occurring biological function inherently present in naturally occurring CRISPR gene editing endonuclease system.
Therefore, the endonuclease system as currently recited in claim 1 does not possess any markedly different characteristics when compared to a naturally occurring CRISPR/Cas system
This judicial exception is not integrated into a practical application because no additional elements are recited in the claims.
The claim does not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claim itself does not recite any additional elements. Thus, claim 1 is rejected under 35 U.S.C. 101 as being drawn to ineligible subject matter as defined in MPEP 2106.
Regarding claims 4-5, 7-9, 12-18, and 23-27 as described below, the claims are also rejected under 35 U.S.C. 101 as they are dependent on claim 1 and do not additionally recite either a markedly different characteristic, a practical application, or significantly more.
Claim 4 is directed towards the limitation requiring a naturally occurring HNH domain in the nuclease as discussed above and disclosed by the instant specification ([00370], [0080]).
Claim 5 is directed towards the limitation requiring a tracrRNA sequence comprising the SEQ ID NO: 5509. The claim refers to naturally occurring guide RNA comprising tracrRNA as discussed above and disclosed by the instant specification ([00153]).
Claims 7-8 are directed towards the limitation requiring guide RNA structures as discussed above. The claims refer to the naturally occurring structures for guide RNA complexed with the nuclease and the guide RNA comprises two RNA polynucleotides wherein one binds the target DNA and other forms a duplex RNA structure or tracrRNA as described in the instant specification ([00380]).
Claim 9 is directed towards the limitation requiring that the guide RNA is complementary to naturally occurring genome as in the instant specification teaches that the CRISPR system is derived from the Phylum Verrucomicrobia, the Phylum Candidatus Peregrinibacteria, or the Phylum Candidatus Melainabacteria based on the sequences of 16S rRNAs ([00370]).
Claim 12 is directed towards the limitation requiring that the DNA repair template comprises homology arms with variable lengths. Given the broadest reasonable interpretation of this claim, the claim limitation is interpreted as the repair template used in the naturally occurring nuclease system, is complementary to a target sequence which is supported by teachings of Boel that discloses that following double stranded DNA break, two main naturally occurring or endogenous repair mechanisms are initiated, one is the error-prone non-homologous end joining pathway and the other is the homology-directed repair or HDR and wherein HDR only activated in the presence of a homologous repair template, naturally provided as the sister chromatid during the G2 and S phase of the cell cycle, leading to the reconstitution of the original sequence (pg. 1, right column, lines 17-24).
Claim 13 is directed towards the limitation requiring that the nuclease system comprises a source of Mg2+. The claim refers to the natural process of endonuclease activity that requires a supply or source of Mg2+ as cofactor which is supported by the teaching of Pingoud that discloses that naturally occurring Type II endonucleases that protect bacteria and archaea against invading DNA, require Mg2+ ions for catalysis (Abstract).
Claim 14 is directed towards the limitation requiring that the endonuclease and the tracrRNA sequence are derived from a bacterial species, i.e. obtained from naturally available CRISPR system.
Claims 16-18 are directed towards the limitation requiring that the guide RNA and the tracrRNA comprise hairpin structures. The instant specification teaches that the guide RNA structure comprises folded structures of gRNA sequences that are computed using Bioinformatic tool and predicted to comprise hairpins ([00386]) as also presented in Figures 21-26wherein the predicted structures correspond to sgRNA of naturally occurring MG nuclease (0067]) The merely predicted structures recited in these claims refer to naturally occurring features and do not include either a markedly different characteristic, or significantly more.
Claim 23 is directed towards the limitation requiring that the PAM sequence is 3’ to the target DNA sequence. Given the broadest reasonable interpretation of this claim and the structural requirement of the naturally occurring CRISPR endonuclease system, PAM is always located 3’ to the target sequence as Wu teaches that the PAM is strictly required to be immediately next to the 3’ end of the target sequence and is recognized by the individual domain in Cas endonuclease (pg. 6, paragraph 4, lines 1-3).
Claims 15 and 24-26 are directed towards the limitation requiring that the endonuclease comprises a sequence with the SEQ ID NO: 1512. The claim refers to the naturally occurring endonuclease sequence of the same MG21 nuclease ([00150]) from which RuvC_III and HNH domains are derived as discussed above.
Claim 27 is directed towards the limitation requiring that the guide RNA structure comprises a sequence with SEQ ID NO: 5473. The claim refers to the guide RNA sequence derived from the naturally occurring MG21-1 nuclease (00467]). Given the broadest reasonable interpretation of this claim the sgRNA is synthetically produced as fusion of two naturally occurring RNA molecules in the CRISPR system that renders naturally occurring features without including markedly different characteristic, or significantly more.
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, 4-5, and 12, are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 105-106, 108-109, 112, and 118 of copending Application No. 18/053,232 in view of Gleditzsch (RNA Biol. 2018 Sep 18;16(4):504–517).
Regarding claims 1 of the instant application, claims 105-106, and 108 of the copending Application No. 18/053,232 claim an RNA-guided nuclease system which is a class 2 type II Cas endonuclease comprising a RuvC_III domain with a SEQ ID NO: 3331 and wherein an engineered guide ribonucleic acid structure is configured to form a complex with said endonuclease, wherein said engineered guide ribonucleic acid (gRNA) structure comprises a guide ribonucleic acid sequence that hybridizes to a target deoxyribonucleic acid sequence. Claim 118 of the copending Application No. 18/053,232 claims that the method of gene editing using endonuclease system comprises DNA repair template comprising homology arms (i.e. interpreted as flanking regions for specific protospacer adjacent motif or PAM sequence as commonly designed and used to determine the target during CRISPR-Cas mediated cleavage and repairing of the target sequence).
Claim 105 of the copending Application No. 18/053,232 does not teach the PAM comprising SEQ ID NO: 5524 of the instant application (claim 1).
However, one of ordinary skill in the art would have considered the teachings of Gleditzsch and Leenay as these are analogous references pertaining to the nuclease system and PAM identification.
Gleditzsch teaches that variants of type II Cas nuclease have flexible PAM recognition such as NGCG or NGAG sequence (i.e. referred to NRNR PAM) (pg. 509, column 1, paragraph 3). Gleditzsch teaches that PAM sequence can be extended to 6 nucleotide length for other Cas orthologs (pg. 509, column 2, paragraph 1).
Leenay teaches the properties of the CRISPR PAM and the emerging tools for determining, visualizing, and engineering PAM recognition (Abstract). Leenay teaches that one of the most common screening methods for functional PAM sequencing is to use the natural ability of CRISPR Cas system to clear foreign genetic material and this property is utilized in a convenient host such as E. Coli (pg. 181, right column, paragraph 2). Leenay teaches that to generate potential PAM sequences, a randomized nucleotide library is inserted next to a target sequence within a plasmid which is transformed into the host and then subjected to next-generation sequencing (pg. 181, right column, paragraph 2). Leenay teaches that investigating PAMs within different CRISPR Cas systems reveals the full range extent of PAM sequences and lengths present in nature, highlighting which sequences may be more readily accessible through PAM engineering (pg. 187, left column, paragraph 1). Leenay also teaches that PAM could be engineered and lengthened to recognize a more specific sequence (pg. 187, left column, paragraph 3).
It would have also been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the PAM sequence of Gleditzsch such that it was engineered to generate 5 bp PAM, as described by Leenay. A person of ordinary skill in the art would have been motivated to do so in order to utilize a nuclease specific PAM sequence and to ensure effective target sequence recognition such that Cas proteins could specifically bind the target and allow the CRISPR-mediated gene editing. A person of ordinary skill in the art would have had a reasonable expectation of success because Gleditzsch teaches the flexible longer (up to 6 bp) PAM recognition by Cas endonucleases while Leenay teaches the engineering aspects of extending any naturally occurring PAMs to fit in broader CRISPR systems or Cas endonuclease types. Therefore modifying the PAM sequence of Gleditzsch such that it was engineered to generate 5 bp PAM, as described by Leenay, would have resulted in the predicable outcome of success.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute the sequence flanked by homology arms of the repair template of the copending Application No. 18/053,232 claims 105-106, and 108 for the PAM sequence of Gleditzsch, modified by Leenay. A person of ordinary skill in the art would have had a reasonable expectation of success because both references teach an engineered nuclease system comprising an RNA-guided endonuclease wherein the endonuclease is a class 2, type II endonuclease. Therefore, since Gleditzsch and Leenay teach flexible design and engineering of PAM sequence compatible for Cas nuclease variants and the copending Application No. 18/053,232 claims 105-106, and 108 teach the engineered class 2, type II Cas endonuclease comprising RuvC_III domain that forms complex with an engineered guide RNA, substituting the sequence flanked by the homology arms of the copending Application No. 18/053,232 claims 105-106, and 108 for the PAM sequence of Gleditzsch modified by Leenay, would have resulted in the predicable outcome of success.
Regarding claim 4, claim 109 of the copending Application No. 18/053,232 is similarly drawn to limitations requiring that the engineered endonuclease system comprises an HNH domain.
Regarding claim 5, claim 112 of the copending Application No. 18/053,232 is similarly drawn to limitations requiring that the guide RNA comprises a SEQ ID NO: 5509.
Regarding claim 12, claim 118 of the copending Application No. 18/053,232 is similarly drawn to limitations requiring that the double-stranded deoxyribonucleic acid repair template comprising from 5' to 3': a first homology arm comprising a sequence of at least 20 nucleotides 5' to the target deoxyribonucleic acid sequence, a synthetic deoxyribonucleic acid sequence of at least 10 nucleotides, and a second homology arm comprising a sequence of at least 20 nucleotides 3' to the target deoxyribonucleic acid sequence.
Closest Prior Art
Regarding claims 10-11, the closest prior art of Sontheimer (PG Pub No. US20140349405 A1) is drawn to an invention related to components and methods for RNA-directed DNA cleavage and gene editing and the components include and the methods utilize a Cas9 protein from Neisseria (Abstract). Sontheimer teaches a type II CRISPR system comprising Cas9 endonuclease, tracrRNA and crRNA and two nuclease domains RuvC and HNH ([0040]). Sontheimer teaches a nuclear localization signal (NLS) where the Cas9 protein is fused at its N-terminus or C-terminus, comprises SEQ ID NO: 5597 with 100% identity ([0069], SEQ ID NO: 5).
Sontheimer does not teach the endonuclease with RuvC_III domain comprising SEQ ID NO: 3331 (claim 1).
Therefore, it would not have been obvious to a person of ordinary skill in the art before the filing date of the claimed invention to substitute the CRISPR Cas endonuclease system comprising RuvC_III with the SEQ ID NO: 3331 for the CRISPR Cas endonuclease system of Sontheimer.
Therefore, if all currently pending 35 U.S.C. 101 and non-statutory double patenting rejections are rectified, the application would be placed in condition for allowance if the limitations of claims 10-11 are rewritten in independent form including all of the limitations of the base claim and any intervening claims
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to FARRUK KABIR whose telephone number is (703)756-5387. The examiner can normally be reached M-F 7:30 - 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, Neil Hammell can be reached on (571) 270-5919. 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.
/FARRUK KABIR/Examiner, Art Unit 1636
/NEIL P HAMMELL/ Supervisory Patent Examiner, Art Unit 1636
Prosecution Insights