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 the restriction requirement in the reply filed on 07/20/2026 is acknowledged. The traversal is on the ground(s) that the art used to argue lack of unity of invention did not teach the gRNA structural feature of comprising a U-rich tail 3’ of the crRNA spacer sequence. This is found persuasive and accordingly, the restriction requirement is withdrawn.
Claims Status
Claims 1-38 is/are currently pending and under examination.
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 – Nucleotide and/or amino acid sequences appearing in the drawings are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). Sequence identifiers for nucleotide and/or amino acid sequences must appear either in the drawings or in the Brief Description of the Drawings.
Required response – Applicant must provide:
Replacement and annotated 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 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.
Fig. 1 contains a nucleic acid sequence with no corresponding SEQ ID NO in the drawing or specification.
Claim Objections
Claims 14, 16 are objected to because of the following informalities: the first “wherein” should be separated from the following limitations by a colon, and each pair of ninth and tenth sequences should be separated from the other pairs of ninth and tenth sequences by a semicolon (e.g., claim 14, “The engineered guide RNA of claim 13, wherein: when the ninth sequence is 5’-A-3’, the tenth sequence is 5’-C-3’;…”), to clarify that the pairs of sequences are alternatives of each other. Appropriate correction is required.
Claim Rejections - 35 USC § 112
112(d):
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 13, 15, 17, 18 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 6 recites that the first sequence is “sequentially linked” to the second sequence, the second sequence is “sequentially linked” to the third sequence, the third sequence is “sequentially linked” to the fourth sequence, the fourth sequence is “sequentially linked” to a linker, the linker is “sequentially linked” to the fifth sequence, and the fifth sequence is “sequentially linked” to the sixth sequence, in a 5’ to 3’ orientation. However, dependent claim 13 recites that a ninth sequence is inserted between the first and second sequences, and a tenth sequence is inserted between the second and third sequences; dependent claim 15 recites that an eleventh sequence is inserted between the fourth sequence and the linker, and a twelfth sequence is inserted between the linker and the fifth sequence; dependent claim 17 recites that a ninth sequence is inserted between the first and second sequences, and a tenth sequence is inserted between the second and third sequences; dependent claim 18 recites that a ninth sequence is inserted between the first and second sequences, and a tenth sequence is inserted between the second and third sequences. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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.
18290467:
Claims 1-26, 33-38 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-23 of copending Application No. 18290467 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other. The copending application recites an engineered guide RNA for use in a CRISPR/Cas12f1 system, comprising a scaffold region of SEQ ID NO:477, which comprises from 5’ to 3’: a sequence 5’-A-3’, instant SEQ ID NO:11, instant SEQ ID NO:12, instant SEQ ID NO:111, and 5’-AUGCAAC-3’ (claims 1-3). The copending application further recites a complex comprising a Cas12f1 protein and the guide RNA (claim 3), DNA or a vector encoding the components of this complex (claims 4-5), and a method of gene editing using this complex (claims 16-23). The copending application recites that the gRNA further comprises a 3’ terminal U-rich tail consisting of the sequence 5’-(UaN)dUe-3’, 5’-UaVUaVUe-3’, or 5’-UaVUaVUaVUe-3’ (claim 1).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 27-32 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-23 of copending Application No. 18290467 in view of Lau (2017).
The copending application recites an engineered guide RNA for use in a CRISPR/Cas12f1 system, comprising a scaffold region of SEQ ID NO:477, which comprises from 5’ to 3’: a sequence 5’-A-3’, instant SEQ ID NO:11, instant SEQ ID NO:12, instant SEQ ID NO:111, and 5’-AUGCAAC-3’ (claims 1-3). The copending application further recites a complex comprising a Cas12f1 protein and the guide RNA (claim 3), DNA or a vector encoding the components of this complex (claims 4-5), and a method of gene editing using this complex (claims 16-23). The copending application recites that the gRNA further comprises a 3’ terminal U-rich tail consisting of the sequence 5’-(UaN)dUe-3’, 5’-UaVUaVUe-3’, or 5’-UaVUaVUaVUe-3’ (claim 1).
However, the copending application does not recite that the vector further comprises a first promoter sequence operably linked to the sequence encoding the Cas endonuclease and a second promoter sequence operably linked to the sequence encoding the gRNA.
Lau teaches that sequences encoding Cas endonucleases and gRNAs should be operably linked to promoter sequences.
Regarding claims 27-32, Lau teaches that sequences encoding Cas endonucleases and gRNAs should be operably linked to promoter sequences (pages 3 and 11, Abstract), and that the promoter operably linked to the sequence encoding a gRNA is “most often” a U6 promoter (page 11, Table 2). It would have been obvious to an artisan that to enable expression of the Cas endonuclease and gRNA encoded in the vectors of the copending application, promoter sequences operably linked to each coding sequence would be required, and adequate promoter sequences for each were known in the art, as taught by Lau.
This is a provisional nonstatutory double patenting rejection.
Subject Matter Not Found in Prior Art
The following is a statement of reasons for the indication of subject matter not found in the prior art: per the limitations of claims 1, 6, 20, 22, 27, and 33, any engineered guide RNA of the instant application must comprise a U-rich tail 3’ of the spacer sequence, wherein the U-rich tail has the sequence (UaN)bUc. While this tail sequence was known in the prior art, it was only known as useful with use of a Cpf1/Cas12a CRISPR endonuclease, and in fact, was known to not be useful with use of a Cas9 CRISPR endonuclease (Bin Moon, 2018, of record). As Cas12a/Cpf1 and Cas12f1/Cas14 (Cas12f1 is a Cas14, see instant specification page 37) are distinct proteins of distinct protein families (see Harrington 2018, e.g. Fig. 1, of record), and because a U-rich tail 3’ of the gRNA spacer sequence is known to be useful for some but not all Type V CRISPR nucleases (Cas12a but not Cas9), it would not have been obvious to an artisan to modify a gRNA for use with a Cas14/Cas12f1 endonuclease to comprise a U-rich tail.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AFRICA M MCLEOD whose telephone number is (703)756-1907. The examiner can normally be reached Mon-Fri 9:00AM-6:00PM EST.
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/AFRICA M MCLEOD/ Examiner, Art Unit 1635
/KIMBERLY CHONG/Primary Examiner, Art Unit 1636
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