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 .
Priority
This Application is a Continuation from Application No. 17/139,678 filed 12/31/2020, which is a Continuation of Application No. 17/020,215 filed 09/14/2020, a Continuation of Application No. 16/680,104 filed 11/11/2019, which is also a Continuation of PCT/US2019/022375 dated 03/14/2019. Applicant’s claim to priority from earliest Provisional Application no. 62/642,919 dated 03/14/2018 is hereby acknowledged.
Application Status
Amendments to claims filed 04/13/2026 are hereby acknowledged. Claim 19 is cancelled. Claims 1-18, 20-33 are pending. Claims 1 and 26-29 are currently amended. Claims 5-7, 9, 16 and 30-33 are withdrawn from consideration after restriction/election.
Therefore, claims 1-4, 8, 10-15, 17-18 and 20-29 are under examination in this office action.
Any objection or rejection not reiterated herein has been overcome by amendments and is therefore withdrawn.
Applicant’s amendments and arguments have been thoroughly reviewed, but are not persuasive to place the claims in condition for allowance for the reasons that follows.
Drawings
The Drawing Replacement sheets and Supplemental file with higher quality and definition filed 12/20/2021 are hereby acknowledged and are acceptable.
Specification
Substitute copy of the Specification filed 04/13/2026 (130 pages) comprising the strike-through and underlined corrections is hereby acknowledged.
Clean copy of the Specification filed 04/13/2026 (120 pages) comprising the corrections is hereby acknowledged and is acceptable.
Non-Statutory Double Patenting
The non-statutory 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 non-statutory 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 non-statutory 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 non-statutory 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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The following rejections are new:
Claims 1, 10-14, 17-18 and 20-29 are rejected on the ground of non-statutory double patenting as being unpatentable over claims 1-3, 7, 9-15, 17-18, 20-21 of the U.S. Patent No. 12,655,421 (formerly co-pending US application 17/020,414; USPAT421).
Regarding claims 1, and 26-27, claim 1 of USPAT421 claims “an engineered, non-naturally occurring Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR) - associated (Cas) system comprising:(a) an RNA guide or a nucleic acid encoding the RNA guide, wherein the RNA guide comprises a direct repeat sequence and a spacer sequence; and (b) a CRISPR-Cas effector protein or a nucleic acid encoding the CRISPR-Cas effector protein, wherein the CRISPR-Cas effector protein comprises the amino acid sequence with at least 95% identity to SEQ ID NO:14 or SEQ ID NO: 16, and the CRISPR-Cas effector protein further comprises at least one nuclear localization signal (NLS), at least one nuclear export signal (NES), or at least one NLS and at least one NES, wherein the CRISPR-Cas effector protein binds to the RNA guide, and wherein the spacer sequence is capable of hybridizing to a target nucleic acid in a eukaryotic cell.”
SEQ ID NOs: 14 and 16 in USPAT421 are species in the claimed genus; both co-pending applications teaches these SEQ ID Nos in Table 4, to be used as a CRISPR-Cas effector proteins that recognize and bind to RNA guide comprising SEQ ID NO: 202 as direct repeat sequence (see Table 4, and see page 49, last paragraph), which sequences encompass the claimed system.
Regarding claims 10-11, claim 7 of USPAT421 claims the spacer sequence between 15 and 47 nt in length. Claim 8 of USPAT421 claims the spacer sequence nucleotide length between 24 and 38.
Regarding claim 12, claim 9 of USPAT421 claims the target nucleic acid comprises a sequence complementary to a nucleotide sequence in the spacer sequence.
Regarding claim 13, claim 2 of USPAT421 claims the system does not include a tracrRNA.
Regarding claim 14, claim 3 of USPAT421 claims the same elements of claim 14.
Regarding claims 17-18, claim 10 of USPAT421 claims the system of claim 1, wherein the CRISPR-Cas effector protein recognizes a protospacer adjacent motif (PAM) sequence, wherein the PAM sequence comprises a nucleotide sequence set forth as 5'-TTN-3', wherein N is any nucleotide.
Regarding claim 20, claim 12 of USPAT421 claims the CRISPR-Cas effector protein further comprises a peptide tag, a fluorescent protein, a base-editing domain, a DNA methylation domain, a histone residue modification domain, a localization factor, a transcription modification factor, a light-gated control factor, a chemically inducible factor, or a chromatin visualization factor.
Regarding claim 21, claim 13 of USPAT421 claims the nucleic acid encoding the CRISPR-Cas effector protein is codon-optimized for expression in a cell.
Regarding claim 22, claim 14 of USPAT421 claims wherein the nucleic acid encoding the CRISPR-Cas effector protein is operably linked to a promoter.
Regarding claim 23, claim 15 of USPAT421claims the nucleic acid encoding the CRISPR-Cas effector protein is in a vector.
Regarding claim 24, claim 15 of USPAT421 claims the nucleic acid encoding the CRISPR-Cas effector protein is in a vector, which encompasses the claimed vectors.
Regarding claim 25, claim 17 of USPAT421 claims the system is present in a delivery system comprising a nanoparticle, a liposome, an exosome, a microvesicle, or a gene-gun.
Regarding claim 26, claim 18 of USPAT421 claims a cell comprising the system of claim 1.
Regarding claim 27, claim 18 of USPAT421 claims a cell comprising the system of claim 1. MPEP 804(II)(B)(1) states,” The portion of the specification of the reference that describes subject matter that falls within the scope of a reference claim may be relied upon to properly construe the scope of that claim. In particular, when ascertaining the scope of the reference’s claim(s) to a compound, the examiner should consider the reference’s specification, including all of the compound’s uses that are disclosed. See Sun Pharm. Indus., 611 F.3d at 1386-88, 95 USPQ2d at 1801-02 (emphasis added).” Co-pending application 17.020,414 teaches that the cell can be eukaryotic or prokaryotic (see page 10, line 20).
Regarding claim 28, claim 20 of USPAT421 claims “the cell is a mammalian cell or a plant cell”.
Regarding claim 29, claim 21 of USPAT421 claims “wherein the cell is a human cell”.
Response to Arguments
Applicant's arguments filed 04/13/2026 have been fully considered but they are not persuasive.
Regarding Applicant’s arguments on page 10 of Remarks, traversing the Non Statutory Double Patenting (NSDP) rejection over co-pending application 17/020,414, Examiner would like to point out that the rejection is no longer a provisional rejection, since the application is now patented, i.e., US Patent No. 12,655,421.
Claim 1 of USPAT421 is drawn to a generic repeat sequence that is recognized by CRISPR-Cas effector proteins with 95% sequence identity with SEQ ID NOs: 14 or 16.
According to the Specification of USPAT421, Table 5A presents SEQ ID NO: 14 as an effector protein recognizing a repeat sequence of SEQ ID NO: 21, which is CCTACAATACCTAAGAAATCCGTCCTAAGTTGACGG. Table %A also presents SEQ ID NO: 16 as recognizing a repeat sequence of SEQ ID NO: 6, which is CCCACAATACCTGAGAAATCCGTCCTACGTTGACGG.
Both sequences fit the generic formula for RNA of instant app.’s SEQ ID NO: 202 , which is 5’-CCGUCNNNNNNUGACGG-3’.
Therefore, regarding the repeat sequences claimed as SEQ ID NO: 202, it is clear that the species of Cas proteins in USPAT421 are able to work with the claimed sequence SEQ ID NO: 202. Therefore, the generic limitation in claim 1 of USPAT421 encompasses the generic sequence for SEQ ID NO: 202.
MPEP 2131.02, part III states that “A generic disclosure will anticipate a claimed species covered by that disclosure when the species can be “at once envisaged” from the disclosure”. In this case, the species are disclosed in Table 5A of the reference USPAT421.
The following rejections are new:
Claims 1-4, 10-13, 15, 17-18 and 20-29 are rejected on the ground of non-statutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. 10,808,245 (USPAT245). Although the claims at issue are not identical, they are not patentably distinct from each other because:
Regarding claims 1, 2 and 15, claim 1 of USPAT245 claims “An engineered, non-naturally occurring Clustered Regularly lnterspaced Short Palindromic Repeat (CRISPR) - associated (Cas) system comprising:
(a) an RNA guide or a nucleic acid encoding the RNA guide, wherein the RNA guide comprises a direct repeat sequence and a spacer sequence; and
(b) a CRISPR-Cas effector protein or a nucleic acid encoding the CRISPR-Cas effector protein, wherein the CRISPR-Cas effector protein comprises an amino acid sequence set forth in SEQ ID NO: 5,
wherein the CRISPR-Cas effector protein binds to the RNA guide, and wherein the spacer sequence binds to a target nucleic acid”.
SEQ ID NO: 5 is a species of the claimed genus in instant application’s claim 1.
SEQ ID NO: 5 of USPAT245 is identical to SEQ ID NO: 5 of instant Application’s claim 15.
MPEP 804(II)(B)(1) states,” The portion of the specification of the reference that describes subject matter that falls within the scope of a reference claim may be relied upon to properly construe the scope of that claim. In particular, when ascertaining the scope of the reference’s claim(s) to a compound, the examiner should consider the reference’s specification, including all of the compound’s uses that are disclosed. See Sun Pharm. Indus., 611 F.3d at 1386-88, 95 USPQ2d at 1801-02 (emphasis added).”
SEQ ID NO: 5 of instant Application is identical to SEQ ID NO: 5 of USPAT245. In the Specification, Table 5A, of USPAT245, SEQ ID NO: 5 recognizes a direct repeat sequence of SEQ ID NO: 10, which is GTTGCAAAACCCAAGAAATCCGTCTTTCATTGACGG. This sequence is encompassed within the generic RNA formula of SEQ ID NO: 202 claimed in instant application’s claim 1 (5’-CCGUNNNNNNUGACGG-3’).
As shown above, the sequence corresponding to the generic SEQ ID NO: 202 is proximal to the 3’ end of the direct repeat sequence, as claimed in instant Application’s claim 2.
USPAT245’s claim 12 is drawn to “The system of claim 1, wherein the CRISPR-Cas effector protein further comprises at least one nuclear localization signal (NLS), at least one nuclear export signal (NES), or at least one NLS and at least one NES”, as in instant Application’s claim 1.
Regarding claim 3, claim 5 of USPAT245 claims the same elements of claim 3 for the direct repeat sequence.
Regarding claim 4, claims 3 and 4 of USPAT245 claim the same sequences SEQ ID NO: 9 and 10 and also sequences 95% identical to the two sequences.
Regarding claim 10, USPAT245’s claim 6 is drawn to a spacer sequence comprising between 15 and 47 nucleotides in length.
Regarding claim 11, USPAT245’s claim 7 is drawn to spacer sequence comprising between 24 and 38 nucleotides in length.
Regarding claim 12, USPAT245’s claim 8 is drawn to target nucleic acid comprising a sequence complementary to the spacer sequence.
Regarding claim 13, claim 2 of USPAT245 claims the system does not include a tracrRNA.
Regarding claims 17-18, claim 9 of USPAT245 claims “the system of claim 1, wherein the CRISPR-Cas effector protein recognizes a protospacer adjacent motif (PAM) sequence, wherein the PAM sequence comprises a nucleotide sequence set forth as 5'-TTN-3', wherein N is any nucleotide”. Claim 10 of USPAT245 claims “the PAM sequence comprises a nucleotide sequence set forth as 5’-TTY-3’, wherein Y is C or T”.
Regarding claim 20, claim 13 of USPAT245 claims the CRISPR-Cas effector protein further comprises a peptide tag, a fluorescent protein, a base-editing domain, a DNA methylation domain, a histone residue modification domain, a localization factor, a transcription modification factor, a light-gated control factor, a chemically inducible factor, or a chromatin visualization factor.
Regarding claim 21, USPAT245’s claim 14 claims the nucleic acid encoding the CRISPR-Cas effector protein is codon-optimized for expression in a cell.
Regarding claim 22, claim 15 of USPAT245 claims wherein the nucleic acid encoding the CRISPR-Cas effector protein is operably linked to a promoter.
Regarding claims 23-24, claims 16-17 of USPAT245 claim the nucleic acid encoding the CRISPR-Cas effector protein is in a vector and recite the same type of vectors.
Regarding claim 25, claim 18 of USPAT245 claims the system is present in a delivery system comprising a nanoparticle, a liposome, an exosome, a microvesicle, or a gene-gun.
Regarding claim 26 , claim 19 of USPAT245 claims “A cell comprising the system of claim 1”.
Regarding claims 27-29, claim 19 of USPAT245 claims a cell.
The USPAT245’s specification teaches that "a cell" is eukaryotic, prokaryotic, bacterial, mammalian, see e.g. page 7. The scope of cell classifications in the instant claims covers human, mammalian, bacterial, plant, eukaryotic, and prokaryotic cells. Therefore, given the information in the USPAT245’s specification, claims 27-29 are prima facie obvious evidenced by applicant's inclusion of a cell.
Allowable Subject Matter
Claim 8 is 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
Claims 1-4, 10-15, 17-18 and 20-29 are rejected. Claim 8 is objected to.
No Claim is allowed.
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/A.D./Examiner, Art Unit 1636
/NANCY J LEITH/Primary Examiner, Art Unit 1636
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