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 without traverse of Group I, claimed in claims 1-17, 20 and 25 in the reply filed on 9/16/25 is acknowledged. Election was made without traverse of APOBEC (species of NMP), XRCC1 (species of BERAP), nCas9 (species of DnaBP) and fusion protein orientation NMP-Dna-BP-BERAP.
Claims 1-17, 20, 25 and 28-30 are pending.
Claims 6-8 and 28-30 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected group, there being no allowable generic or linking claim.
Please note that the prior art presented below not only teaches the elected species of nCas9 but also the non-elected species of dCas. Accordingly, claim 12 is under consideration.
Claims 1-5, 9-17, 20 and 25 read on the elected Group I and elected species and are under consideration.
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.
Claims 1-2, 9-13, 15-16 and 25 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Liu et al. (WO2017/070632).
With respect to claims 1 and 2, Liu et al. teach and claim a fusion protein comprising: (i) a cas9 domain; (ii) a cytidine deaminase domain and (iii) a uracil glycosylase inhibitor (UGI) domain (claim 1, Abstract).
With respect to the limitation “a DnaBP”, as evidenced by claim 9-10, cas9 is a DnaBP.
With respect to the limitation “a Base Excision Repair associated protein (BERAP), the instant specification defines “BERAP” as any protein that is involved in the base excision repair pathway [PGPUB0066]. UGI blocks uracil glycosylase (enzyme that initiates base excision repair by removing uracil from DNA. Therefore, UGI meets the broadest reasonable interpretation of BERAP since it blocks initiation of base excision repair (i.e. modulates base excision repair pathway).
With respect to the limitation “nucleobase modifying protein”, as evidenced by claim 2, cytosine deaminase domain is a nucleobase modifying protein”.
The fusion protein of Liu et al. does not include a uracil binding protein or a catalytically active DNA polymerase.
The fusion protein of Liu et al. does not comprise a uracil binding protein or catalytically active DNA polymerase. Therefore, the fusion protein of Liu (claim 1) anticipates instant claims 1 and 2.
With respect to claims 9-11, Liu et al. teach and claim the Cas9 domain is a Cas9 nickase (nCas9) (claim 3). Fig. 47 discloses the schematic of a fusion protein comprising humanAPOBEC3G-XTEN—nCas9-UGI-NLS.
With respect to claim 12, Liu et al. teach the fusion proteins of Cas9 (e.g. dCas9 or nCas9) [0012]. Liu et al. also claim a fusion protein comprising (i) dCas9, (ii) a nucleic acid editing domain and (iii) UGI (claim 44), wherein the nucleic acid editing domain comprises a cytidine deaminase (claim 75).
With respect to claim 13, Liu et al. teach and claim the cytosine deaminase is APOBEC (claim 76). Fig. 47 discloses the schematic of a fusion protein comprising humanAPOBEC3G-XTEN—nCas9-UGI-NLS.
With respect to claims 15-16, Liu et al. teach and claim the orientation of the fusion protein is [nucleic acid editing domain]-[dCas9 domain]-[UGI], meeting the limitation of the orientation of [NMP]-[DnaBP]-[BERAP] (claim 72 and Fig. 47).
With respect to claim 25, Liu et al. teach and claim polynucleotides encoding the fusion proteins. Liu et al. also teach vectors comprising such polynucleotides (claims 297-299 and [0033,00282]).
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.
Claims 1-5, 9-16 and 25 are rejected under 35 U.S.C. 103 as being unpatentable over Liu et al. (WO2017/070632) in view of London et al. (DNA Repair (Amst) 2015 June; 30:90-103, cited on IDS and provided by Applicants).
The teachings of Liu et al. are presented in detail above. Liu et al. does not teach the BERAP is XRCC1. However, the teachings of London et al. cure this deficiency.
London teaches that XRCC1 is a protein involved in the base excision repair pathway. London et al. teach scaffold proteins play a central role in DNA repair by recruiting and organizing sets of enzymes required to perform the multi-step repair process (Abstract).
With respect to claims 3-5 and 14, It would have been obvious to a person of ordinary skill in the art before the effective filing date of the invention to employ XRCC1 as the base excision repair associated protein in the fusion protein of Liu et al. in view of the well established role of XRCC1 as a protein involved in the base excision repair pathway. Liu et al. teach that the outcomes of nucleobase modification are influenced by processing through the base excision repair pathway [0065]. XRCC1 was known to function as a scaffold protein that coordinates and recruits base excision repair factors at sites of DNA damage and thus represents a known alternative base excision repair associated protein. There is a reasonable expectation of success given XRCC1’s established involvement in base excision repair at the time of the invention.
Claims 1-5, 9-17, 20 and 25 are rejected under 35 U.S.C. 103 as being unpatentable over Liu et al. (WO2017/070632) and London et al. (DNA Repair (Amst) 2015 June; 30:90-103, cited on IDS and provided by Applicants) in view of NCBI WP_306789577.1 (2005), NCBI NP_037039.1 and NCBI NP_033558.2 (2008).
Liu et al. does not teach the sequence of Cas9, APOBEC and XRCC1. However, the teachings of WP_306789577.1 (Cas9), NP_037039.1 (APOBEC) and NP_033558.2 (XRCC1) cure this deficiency.
The NCBI teaches the sequence of Cas9 is WP_306789577.1 and is a 100% identical to instantly claimed SEQ ID NO: 1. The NCBI teaches the sequence of NP_037039.1 and is a 100% identical to instantly claimed SEQ ID NO: 3.
NCBI teaches the sequence of XRCC1 is NP_033558.2 and is a 100% identical to instantly claimed SEQ ID NO: 4.
With respect to claim 17, it would have been obvious to a person of ordinary skill in the art to create the fusion protein of Liu et al. and London et al. using the NCBI sequences above in order to derive the fusion protein because NCBI teaches the amino acid sequence of each component and the sequences are 100% identical to the claimed sequences. There is a reasonable expectation of success given that the sequences are well established in the art and available in NCBI database.
With respect to claim 20, Liu et al. teach protein complexes [0030-0031]. It would have been obvious to a person of ordinary skill in the art to create a protein complex of Liu et al. and London et al. using the NCBI sequences above in order to derive the protein complex because NCBI teaches the amino acid sequence of each component and the sequences are 100% identical to the claimed sequences. There is a reasonable expectation of success given that the sequences are well established in the art and available in NCBI database.
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 1-2, 9-13, 15-16 and 25 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-26 of U.S. Patent No. USPN 11,268,082. Although the claims at issue are not identical, they are not patentably distinct from each other because the USPN anticipates the instant claims.
The USPN claims a fusion protein comprising a napDNAbp, a cytidine deaminase domain and two UGI domains, wherein the napDNAbp is CasX, CasY..or argonaute protein. The USPN also claims a complex of the components (claims 1-2). The USPN claims the cytidine deaminase is APOBEC (claim 11). The USPN claim polynucleotides encoding the fusion protein (claims 13-16). The USPN claims the orientation of the fusion protein (claim 23). The fusion protein of the USPN anticipates instant claims 1-2, 9-13, 15-16 and 25.
Claims 1-5, 9-16 and 25 are rejected on the grounds of nonstatuutory double patenting as being unpatentable over claims 1-26 of U.S. Patent No. USPN 11,268,082 in view of London et al. (DNA Repair (Amst) 2015 June; 30:90-103, cited on IDS and provided by Applicants).
The USPN does not teach the BERAP is XRCC1. However, the teachings of London et al. cure this deficiency.
The teachings of London et al. are presented in detail above.
With respect to claims 3-5 and 14, It would have been obvious to a person of ordinary skill in the art before the effective filing date of the invention to employ XRCC1 as the base excision repair associated protein in the fusion protein of the USPN in view of the well-established role of XRCC1 as a protein involved in the base excision repair pathway. XRCC1 was known to function as a scaffold protein that coordinates and recruits base excision repair factors at sites of DNA damage and thus represents a known alternative base excision repair associated protein. There is a reasonable expectation of success given XRCC1’s established involvement in base excision repair at the time of the invention.
Claims 1-5, 9-17, 20 and 25 are rejected on the grounds of nonstatuutory double patenting as being unpatentable over claims 1-26 of U.S. Patent No. USPN 11,268,082 and London et al. (DNA Repair (Amst) 2015 June; 30:90-103, cited on IDS and provided by Applicants) in view of NCBI WP_306789577.1 (2005), NCBI NP_037039.1 and NCBI NP_033558.2 (2008).
The USPN and London et al. do not teach the sequence of Cas9, APOBEC and XRCC1. However, the teachings of WP_306789577.1 (Cas9), NP_037039.1 (APOBEC) and NP_033558.2 (XRCC1) cure this deficiency.
The NCBI teaches the sequence of Cas9 is WP_306789577.1 and is a 100% identical to instantly claimed SEQ ID NO: 1.
The NCBI teaches the sequence of APOBEC is NP_037039.1 and is a 100% identical to instantly claimed SEQ ID NO: 3.
NCBI teaches the sequence of XRCC1 is NP_033558.2 and is a 100% identical to instantly claimed SEQ ID NO: 4.
With respect to claims 17 and 20, it would have been obvious to a person of ordinary skill in the art to create the fusion protein or complex using the NCBI sequences above in order to derive the fusion protein because NCBI teaches the amino acid sequence of each component and the sequences are 100% identical to the claimed sequences. There is a reasonable expectation of success given that the sequences are well established in the art and available in NCBI database.
Claims 1-2, 9-13, 15-16 and 25 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 208-228 of copending application 18/066,878. Although the claims at issue are not identical, they are not patentably distinct from each other because the copending application anticipates the instant claims.
The copending application claims a method for producing a RNP complex comprising complexing a napDNAbp, cytidine deaminase and at least two UGI domains. comprising a napDNAbp, a cytidine deaminase domain and two UGI domains, wherein the napDNAbp is CasX, CasY, dCas9, Cas9 nickase or Argonaute protein, wherein the cytidine deaminase is APOBEC (claims 208-224). The copending application claims the orientation of the complex or fusion protein (claim 225). The fusion protein/complex of the copending application anticipates instant claims 1-2, 9-13, 15-16 and 25.
Claims 1-5, 9-16 and 25 are rejected on the grounds of nonstatuutory double patenting as being unpatentable over claims 208-228 of copending application 18/066,878 in view of London et al. (DNA Repair (Amst) 2015 June; 30:90-103, cited on IDS and provided by Applicants).
The copending application does not teach the BERAP is XRCC1. However, the teachings of London et al. cure this deficiency.
The teachings of London et al. are presented in detail above.
With respect to claims 3-5 and 14, It would have been obvious to a person of ordinary skill in the art before the effective filing date of the invention to employ XRCC1 as the base excision repair associated protein in the fusion protein of the copending application in view of the well-established role of XRCC1 as a protein involved in the base excision repair pathway. XRCC1 was known to function as a scaffold protein that coordinates and recruits base excision repair factors at sites of DNA damage and thus represents a known alternative base excision repair associated protein. There is a reasonable expectation of success given XRCC1’s established involvement in base excision repair at the time of the invention.
Claims 1-5, 9-17, 20 and 25 are rejected on the grounds of nonstatuutory double patenting as being unpatentable over claims 208-228 of copending application 18/066,878 and London et al. (DNA Repair (Amst) 2015 June; 30:90-103, cited on IDS and provided by Applicants) in view of NCBI WP_306789577.1 (2005), NCBI NP_037039.1 and NCBI NP_033558.2 (2008).
The copending Application and London et al. do not teach the sequence of Cas9, APOBEC and XRCC1. However, the teachings of WP_306789577.1 (Cas9), NP_037039.1 (APOBEC) and NP_033558.2 (XRCC1) cure this deficiency.
The NCBI teaches the sequence of Cas9 is WP_306789577.1 and is a 100% identical to instantly claimed SEQ ID NO: 1.
The NCBI teaches the sequence of APOBEC is NP_037039.1 and is a 100% identical to instantly claimed SEQ ID NO: 3.
NCBI teaches the sequence of XRCC1 is NP_033558.2 and is a 100% identical to instantly claimed SEQ ID NO: 4.
With respect to claims 17 and 20, it would have been obvious to a person of ordinary skill in the art to create the fusion protein or complex using the NCBI sequences above in order to derive the fusion protein because NCBI teaches the amino acid sequence of each component and the sequences are 100% identical to the claimed sequences. There is a reasonable expectation of success given that the sequences are well established in the art and available in NCBI database.
Conclusion
No claims are allowed.
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/TARA L MARTINEZ/ Examiner, Art Unit 1654