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 .
Applicant’s amendments to the claims dated 2/9/24 are acknowledged. Claims 1-35 are pending. Claims 2, 3, 20, 31 and 35 are amended. Prosecution on the merits begins for claims 1-35.
PRIORITY
The instant application, filed 10/11/2023 is a continuation of US Patent No. 11,820,997, which is a CONTINUATION of US Patent No. 10,711,280, filed 12/18/2018, which is a CONTINUATION of US Patent No. 10,208,317, filed 11/17/2016, which is a DIVISIONAL of US Patent No. 9,546,384 filed 10/15/2014, which claims priority to US Provisional Application No. 62/064,384, filed 10/15/2014; US Provisional Application No. 62/059,527, filed 10/03/2014; US Provisional Application No. 62/052,906, filed 9/19/2014; US Provisional Application No. 62/029,261, filed 7/25/2014; US Provisional Application No. 62/017,416, filed 06/26/2014, and US Provisional Application No. 61/914,768, filed 12/11/2013. Thus, the earliest possible priority for the instant application is 12/11/2013.
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Provisional Application No. 61/914,768, filed 12/11/2013, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. All currently pending claims are directed to a method for modifying a mouse ES cell using a CRISPR system and a long targeting vector. Provisional Application No. 61/914,768, filed 12/11/2013 does not teach or suggest modifying mouse ES cells. The application is directed to modification of rat ES cells.
Thus, currently pending claims 1-35 are afforded priority to US Provisional Application No. 62/017,416, filed 06/26/2014.
CLAIMS
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Instant claim 1 is directed to a method of genetically inserting a nucleic acid into a targeted genomic location in a mouse embryonic stem cell using a CRISPR system, wherein the method comprises utilizing a large targeting vector (LTVEC) of at least 10kb that comprises the nucleic acid insert, wherein the insert is at least 30kb, or the genomic location that is targeted spans at least 30kb.
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.
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Claims 1-35 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-73 of U.S. Patent No. 11,820,997. Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are obvious variants of the patented claims.
Instant claim 1 is presented above, and is directed to a method of genomic modification comprising a cas9 protein, a CRISPR RNA (crRNA), a tracrRNA and a LTVEC comprising a DNA insert of at least 30 kb, wherein the insert comprises a 5’ and a 3’ homology arm, wherein the insertion is of at least 30 kb, or wherein the target 5’ and 3’ regions on the genome are separated by at least 30 kb.
Instant dependent claim 17 of the instant application requires wherein the sum total of the 5’ homology arm and 3’ homology arm is at least 10 kb.
Claim 1 of the ‘997 patent is directed to a method of genomic modification comprising a cas9 protein, a crRNA, a tracrRNA and a LTVEC comprising a DNA insert of at least 20 kb, wherein insert comprises a 5’ homology arm of at least 5 kb, and a 3’ homology arm of at least 5kb, that results in an insertion of at least 20 kb.
Dependent claim 69 of the ‘997 patent requires wherein the sum total of the 5’ homology arm and 3’ homology arm is at least 10 kb.
Dependent claim 36 of the ‘997 patent requires wherein the insertion of the insert at the genomic locus is at least 30 kb.
It would have been obvious to arrive at instant claim 1 from claims 1, 32 and 36 of the ‘997 patent.
Instant claims 2-6 are similar in scope or obvious over patented claims 2-6 regarding the forms of the cas9 and gRNA when introduced into the ES cells, one or more transcripts, protein/RNA complex, etc., the structure of the crRNA and tracrRNA.
Instant claims 7-8, 18, 19, 35 are similar in scope or obvious over patented claims 13-15, 33-36 regarding the deletions of endogenous nucleic acids and insertion of the insert nucleic acid.
Instant claims 9-13 are similar in scope or obvious over patented claims 16-19 regarding biallelic modification.
Instant claims 14, 17 are similar in scope or obvious over patented claims 30, 67, 69, 71 regarding the size of the LTVECs and the size of the homology arms.
Instant claim 16 is similar in scope or obvious over patented claim 20 regarding placement of the CRISPR target sequence flanked by a PAM sequence.
Instant claims 23-33 are similar in scope or obvious over patented claims 21-22, 33, 39-45, and 52-57 regarding the modifications to the genome at immunoglobin genes and/or insertions of immunoglobin genes.
Instant claim 15, 20 are similar in scope or obvious over patented claims 7-10 regarding insert/insertion sizes.
Instant claim 21 is similar in scope or obvious over patented claim 33, 37, 65 regarding the CRISPR target sequence within the native genome, or targets a sequence that was integrated into the genome.
Instant claim 22 is similar in scope or obvious over patented claim 53 regarding the targeted genomic locus of interest selected from a Markush group.
Instant claim 34 is similar in scope or obvious over patented claim 57 regarding the insert comprises a disease allele.
Thus, the instant claims are obvious variants of the patented claims.
Claims 1-35 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-69 of U.S. Patent No. 10,711,280. Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are an obvious variant of the patented claims.
Instant claim 1 is presented above, and is directed to a method of genomic modification comprising a cas9 protein, a CRISPR RNA (crRNA), a tracrRNA and a LTVEC comprising a DNA insert of at least 30 kb, wherein the insert comprises a 5’ and a 3’ homology arm, wherein the insertion is of at least 30 kb, or wherein the target 5’ and 3’ regions on the genome are separated by at least 30 kb.
Claim 1 of the ‘280 patent is directed to a method of genomic modification comprising a cas9 protein, a crRNA, a tracrRNA and a LTVEC comprising a DNA insert, that results in an insertion or deletion of at least 30 kb.
Claim 64 of the ‘280 patent requires wherein the total sum of the 3’ and 5’ homology arms of the LTVEC is at least 10 kb.
It would have been obvious to arrive at instant claim 1 from claims 1 and 64 of the ‘280 patent.
Instant claims 2-6 are similar in scope or obvious over patented claims 11-16 regarding the forms of the cas9 and gRNA when introduced into the ES cells, one or more transcripts, protein/RNA complex, etc., the structure of the crRNA and tracrRNA.
Instant claims 7-8, 18, 19, 35 are similar in scope or obvious over patented claims 17-18, 23-24, 28-31, 46-52, 54-56, 58-61, 68 regarding the deletions of endogenous nucleic acids and insertion of the insert nucleic acid.
Instant claims 9-13 are similar in scope or obvious over patented claims 19-22 regarding biallelic modification.
Instant claims 14, 17 are similar in scope or obvious over patented claims 23, 27, 62, 34, 66 regarding the size of the LTVECs and the size of the homology arms.
Instant claim 16 is similar in scope or obvious over patented claim 26 regarding placement of the CRISPR target sequence flanked by a PAM sequence.
Instant claims 23-33 are similar in scope or obvious over patented claims 34-45 regarding the modifications to the genome at immunoglobin genes and/or insertions of immunoglobin genes.
Instant claims 15, 20 are similar in scope or obvious over patented claims 24-25 regarding insert/insertion sizes.
Instant claim 21 is similar in scope or obvious over patented claims 32-33, 65, 66, 68 regarding the CRISPR target sequence within the native genome, or targets a sequence that was integrated into the genome.
Instant claim 22 is similar in scope or obvious over patented claim 53 regarding the targeted genomic locus of interest selected from a Markush group.
Instant claim 34 is similar in scope or obvious over patented claim 57 regarding the insert comprises a disease allele.
Thus, the instant claims are obvious variants of the patented claims.
Claims 1-35 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-61 of U.S. Patent No. 10,208,317. Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are an obvious variant of the patented claims.
Instant claim 1 is presented above, and is directed to a method of genomic modification comprising a cas9 protein, a CRISPR RNA (crRNA), a tracrRNA and a LTVEC comprising a DNA insert of at least 30 kb, wherein the insert comprises a 5’ and a 3’ homology arm, wherein the insertion is of at least 30 kb, or wherein the target 5’ and 3’ regions on the genome are separated by at least 30 kb.
Claim 1 of the ‘317 patent is directed to a method of genomic modification comprising a cas9 protein, a crRNA, a tracrRNA and a LTVEC comprising a DNA insert, that results in an insertion or deletion of at least 30 kb.
The instantly claimed requirement wherein the insert is at least 30 kb is obvious over the insert of at least 30 kb of the patented claims. Thus, instant claim 1 is an obvious variant of the patented claim.
Instant claims 2-6 are similar in scope or obvious over patented claims 2-8 regarding the forms of the cas9 and gRNA when introduced into the ES cells, one or more transcripts, protein/RNA complex, etc., the structure of the crRNA and tracrRNA.
Instant claims 7-8, 18, 19, 35 are similar in scope or obvious over patented claims 9-10, 16-17, 21-24, 45-51, 53-55, 58-60 regarding the deletions of endogenous nucleic acids and insertion of the insert nucleic acid.
Instant claims 9-13 are similar in scope or obvious over patented claims 11-15 regarding biallelic modification.
Instant claims 14, 17 are similar in scope or obvious over patented claims 16, 20, 61 regarding the size of the LTVECs and the size of the homology arms.
Instant claim 16 is similar in scope or obvious over patented claim 19 regarding placement of the CRISPR target sequence flanked by a PAM sequence.
Instant claims 23-33 are similar in scope or obvious over patented claims 27-44 regarding the modifications to the genome at immunoglobin genes and/or insertions of immunoglobin genes.
Instant claim 15, 20 are similar in scope or obvious over patented claims 18, 21, regarding insert/insertion sizes.
Instant claim 21 is similar in scope or obvious over patented claims 25-26 regarding the CRISPR target sequence within the native genome, or targets a sequence that was integrated into the genome.
Instant claim 22 is similar in scope or obvious over patented claim 52 regarding the targeted genomic locus of interest selected from a Markush group.
Instant claim 34 is similar in scope or obvious over patented claim 56-57 regarding the insert comprises a disease allele.
Thus, the instant claims are obvious variants of the patented claims.
Claims 1-21 and 35 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-26 of U.S. Patent No. 9,546,384. Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are an obvious variant of the patented claims.
Instant claim 1 is presented above, and is directed to a method of genomic modification comprising a cas9 protein, a CRISPR RNA (crRNA), a tracrRNA and a LTVEC comprising a DNA insert of at least 30 kb, wherein the insert comprises a 5’ and a 3’ homology arm, wherein the insertion is of at least 30 kb, or wherein the target 5’ and 3’ regions on the genome are separated by at least 30 kb.
Claim 1 of the ‘384 patent is directed to a method of producing an F0 generation mouse comprising the genomic modification comprising a cas9 protein, a crRNA, a tracrRNA and a LTVEC comprising a DNA insert, that results in an insertion or deletion of at least 30 kb.
The instant claim is an obvious variant encompassed by the claims of the patent during the process of making the mice. Thus, the instant claims are an obvious variant of the patented claims.
Instant claims 2-6 are similar in scope or obvious over patented claims 2-7, 22 regarding the forms of the cas9 and gRNA when introduced into the ES cells, one or more transcripts, protein/RNA complex, etc., the structure of the crRNA and tracrRNA.
Instant claims 7-8, 18, 19, 35 are similar in scope or obvious over patented claims 8, 14, 17, 19-21, 24 regarding the deletions of endogenous nucleic acids and insertion of the insert nucleic acid.
Instant claims 9-13 are similar in scope or obvious over patented claims 9-13 regarding biallelic modification.
Instant claims 14, 17 are similar in scope or obvious over patented claims 16 regarding the size of the LTVECs and the size of the homology arms.
Instant claim 16 is similar in scope or obvious over patented claim 23 regarding placement of the CRISPR target sequence flanked by a PAM sequence.
Instant claim 15, 20 are similar in scope or obvious over patented claims 17 , 18, 19, 21, 24 regarding insert/insertion sizes.
Instant claim 21 is similar in scope or obvious over patented claims 25-26 regarding the CRISPR target sequence within the native genome, or targets a sequence that was integrated into the genome.
Thus, the instant claims are obvious variants of the patented claims.
Claims 1-20, 35 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-24 of U.S. Patent No. 9,228,208. Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are an obvious variant of the patented claims.
Instant claim 1 is presented above, and is directed to a method of genomic modification comprising a cas9 protein, a CRISPR RNA (crRNA), a tracrRNA and a LTVEC comprising a DNA insert of at least 30 kb, wherein the insert comprises a 5’ and a 3’ homology arm, wherein the insertion is of at least 30 kb, or wherein the target 5’ and 3’ regions on the genome are separated by at least 30 kb.
Claim 1 of the ‘208 patent is directed to a method of genomic modification comprising a cas9 protein, a crRNA, a tracrRNA and a LTVEC comprising a DNA insert, that results in an insertion or deletion of at least 30 kb.
Thus, the instant claim is an obvious variant of the patented claim.
Instant claims 2-6 are similar in scope or obvious over patented claims 2-8 regarding the forms of the cas9 and gRNA when introduced into the ES cells, one or more transcripts, protein/RNA complex, etc., the structure of the crRNA and tracrRNA.
Instant claims 7-8, 18, 19, 35 are similar in scope or obvious over patented claims 9-10, 16-17, 21-24 regarding the deletions of endogenous nucleic acids and insertion of the insert nucleic acid.
Instant claims 9-13 are similar in scope or obvious over patented claims 11-15, regarding biallelic modification.
Instant claims 14, 17 are similar in scope or obvious over patented claims 16, 20 regarding the size of the LTVECs and the size of the homology arms.
Instant claim 16 is similar in scope or obvious over patented claim 19 regarding placement of the CRISPR target sequence flanked by a PAM sequence.
Instant claim 15, 20 are similar in scope or obvious over patented claims 17-18 regarding insert/insertion sizes.
Thus, the instant claims are obvious variants of the patented claims.
Conclusion
No claims are allowed.
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KAA
/CHRISTOPHER M BABIC/Supervisory Patent Examiner, Art Unit 1633
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