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, Claims 1-6 and 22-29, in the reply filed on 8 December 2025 is acknowledged.
Claims 7-8, 10-11, 14-16, 20, and 30 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 8 December 2025.
Applicant is reminded that upon the cancelation of claims to a non-elected invention, the inventorship must be corrected in compliance with 37 CFR 1.48(a) if one or more of the currently named inventors is no longer an inventor of at least one claim remaining in the application. A request to correct inventorship under 37 CFR 1.48(a) must be accompanied by an application data sheet in accordance with 37 CFR 1.76 that identifies each inventor by his or her legal name and by the processing fee required under 37 CFR 1.17(i).
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, specifically FIGs. 1-1, 1-2, and 1-3, 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.
Claim Rejections - 35 USC § 103
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 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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1-6 and 22-30 is/are rejected under 35 U.S.C. 103 as being unpatentable over Osakabe (PG Pub No: CA 3,073,372, published 19 February 2019) in view of Lin (Nucleic Acids Research 48.18 (9 October 2020): 10470-10478).
Regarding claims 1, 22, and 25, Osakabe is drawn towards a method for targeting a target nucleotide sequence (Abstract). Osakabe teaches the use of a complex for altering a target nucleotide sequence comprising (i) CRISPR type I-D associated proteins Cas3d, Cas5d, Cas6d, Cas7d and Cas10d, and (ii) a guide RNA comprising a sequence complementary to a target nucleotide sequence, and common repetitive sequences derived from a CRISPR locus, preceding and following the complementary sequence (i.e., a crRNA) ([0061]; pg. 70; see Claim 6). Osakabe teaches the use of a plasmid encoding the Cas3d, Cas5d, Cas6d, Cas7d, Cas10d, and a crRNA (pg. 12; see FIG. 2). Osakabe teaches that the method may be performed in vitro (i.e., the target nucleotide sequence may be isolated) ([0026]).
Osakabe does not teach or suggest the use of a polypeptide containing the N-terminal HD domain of Casd10 (Claims 1, 22, and 25). Osakabe does not teach or suggest the use of a polypeptide that does not contain the N-terminal HD domain of a Cas10d and contains a C-terminal partial sequence of Cas10d (Claims 1, 22, and 25).
However, one of ordinary skill in the art would have considered the teachings of Lin as both references are common fields of endeavor pertaining to the use of Cas10d proteins.
Lin is drawn towards a study concerned with a subtype I-D CRISPR system (Abstract). Lin teaches that the subtype I-D system comprises a Cas10d endonuclease HD domain, termed Cas3", and a helicase domain, termed Cas3’ (pg. 10471, 10476; see Figure 1A). Lin teaches that the N-terminus of the Cas10d protein comprises the HD domain (pg. 10471, 10476; see Figure 1A). Lin teaches that Cas3d comprises a helicase domain, termed Cas3' that can unwind target dsDNA and allow for the Cas3" to nick the non- target DNA strand (pg. 10470). Lin teaches that the Cas3" was able to be separated from the subtype I-D system (i.e., resulting in two polypeptides: one containing the N-terminal HD domain of Casd10 and one that does not contain the N-terminal HD domain of a Cas10d and contains a C-terminal partial sequence of Cas10d) and merged to Cas3' such that the system was transformed from a dormancy-based immune system into an immune system that can directly degrade invasive genomes (pg. 10476).
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 Cas10d of Osakabe for a polypeptide containing the N-terminal HD domain of Casd10 and a polypeptide that does not contain the N-terminal HD domain of a Cas10d and contains a C-terminal partial sequence of Cas10d, as described by Lin. A person of ordinary skill in the art would have been motivated to do so in order to transform a dormancy-based immune system into an immune system that can directly degrade invasive genomes following the merger of the N-terminal HD domain with the Cas3. A person of ordinary skill in the art would have had a reasonable expectation of success because both Osakabe and Lin teach the use of subtype I-D CRISPR systems comprising functional Cas10d polypeptides.
Regarding claims 2 and 26, Osakabe teaches the use of a Cas3d protein ([0061]; pg. 70; see Claim 6).
Regarding claims 3 and 27, Osakabe teaches that the method can be utilized to alter gene expression via transcriptional activation or inactivation ([0085]).
Regarding claims 4 and 28, Lin teaches that the C-terminal portion of the Cas10d is at least 127 amino acids in length (pg. 10473).
Regarding claims 5 and 29, Osakabe teaches that the method can be performed in a eukaryotic cell ([0015]).
Regarding claim 6, Osakabe teaches that the alternation can be a deletion, insertion, or substitution ([0036]).
Regarding claim 23, Osakabe teaches that the method may be performed in a plant cell ([0015]).
Regarding claim 24, Osakabe teaches that the method may be performed in a non-human animal cell ([0015]).
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, 4, 6, 22, and 28 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 3 of U.S. Patent No. 12,012,596 in view of Lin (Nucleic Acids Research 48.18 (9 October 2020): 10470-10478).
Regarding claims 1, 22, and 25, patented claim 1 claims a method for altering a target nucleotide sequence, the method comprising (a) introducing into a cell: (i) one or more expression cassettes comprising nucleic acids encoding CRISPR type I-D associated proteins Cas3d, Cas5d, Cas6d, Cas7d and Cas10d, and (ii) a guide RNA comprising (1) a sequence complementary to the target nucleotide sequence and (2) common repetitive sequences derived from a CRISPR locus, preceding and following the complementary sequence, or a DNA encoding the guide RNA (see patented Claim 1).
Patented claim 1 does not claim the use of a polypeptide containing the N-terminal HD domain of Casd10 (Claims 1, 22, and 25). Patented claim 1 does not claim the use of a polypeptide that does not contain the N-terminal HD domain of a Cas10d and contains a C-terminal partial sequence of Cas10d (Claims 1, 22, and 25).
However, one of ordinary skill in the art would have considered the teachings of Lin as both references are common fields of endeavor pertaining to the use of Cas10d proteins.
Lin is drawn towards a study concerned with a subtype I-D CRISPR system (Abstract). Lin teaches that the subtype I-D system comprises a Cas10d endonuclease HD domain, termed Cas3", and a helicase domain, termed Cas3’ (pg. 10471, 10476; see Figure 1A). Lin teaches that the N-terminus of the Cas10d protein comprises the HD domain (pg. 10471, 10476; see Figure 1A). Lin teaches that Cas3d comprises a helicase domain, termed Cas3' that can unwind target dsDNA and allow for the Cas3" to nick the non- target DNA strand (pg. 10470). Lin teaches that the Cas3" was able to be separated from the subtype I-D system (i.e., resulting in two polypeptides: one containing the N-terminal HD domain of Casd10 and one that does not contain the N-terminal HD domain of a Cas10d and contains a C-terminal partial sequence of Cas10d) and merged to Cas3' such that the system was transformed from a dormancy-based immune system into an immune system that can directly degrade invasive genomes (pg. 10476).
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 patented Cas10d for a polypeptide containing the N-terminal HD domain of Casd10 and a polypeptide that does not contain the N-terminal HD domain of a Cas10d and contains a C-terminal partial sequence of Cas10d, as described by Lin. A person of ordinary skill in the art would have been motivated to do so in order to transform a dormancy-based immune system into an immune system that can directly degrade invasive genomes following the merger of the N-terminal HD domain with the Cas3. A person of ordinary skill in the art would have had a reasonable expectation of success because both the patented claims and Lin teach the use of subtype I-D CRISPR systems comprising functional Cas10d polypeptides.
Regarding claims 2 and 26, patented claim 1 claim the use of a Cas3d protein.
Regarding claims 4 and 28, Lin teaches that the C-terminal portion of the Cas10d is at least 127 amino acids in length (pg. 10473).
Regarding claim 6, patented claim 3 claims that the alternation can be a deletion, insertion, or substitution.
Claims 3, 5, 23-27, and 29 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 3 of U.S. Patent No. 12,012,596 in view of Lin (Nucleic Acids Research 48.18 (9 October 2020): 10470-10478) as described above, further in view of Osakabe (PG Pub No: CA 3,073,372, published 19 February 2019).
Regarding claims 3, 5, 23-27, and 29, claims 1 and 3 of US Patent No. 12,012,596 in view of Lin renders obvious claims 1-2, 4, 6, 22, 25-26, and 28 as described above.
Regarding claims 3 and 27, claims 1 and 3 of US Patent No. 12,012,596 in view of Lin does not teach or suggest that the method can be utilized to alter gene expression via transcriptional activation or inactivation (Claims 3 and 27).
However, one of ordinary skill in the art would have considered the teachings of Osakabe as both references are common fields of endeavor pertaining to the use of CRISPR type I-D systems.
Osakabe is drawn towards a method for targeting a target nucleotide sequence (Abstract). Osakabe teaches the use of a complex for altering a target nucleotide sequence comprising (i) CRISPR type I-D associated proteins Cas3d, Cas5d, Cas6d, Cas7d and Cas10d, and (ii) a guide RNA comprising a sequence complementary to a target nucleotide sequence, and common repetitive sequences derived from a CRISPR locus, preceding and following the complementary sequence (i.e., a crRNA) ([0061]; pg. 70; see Claim 6). Osakabe teaches the use of a plasmid encoding the Cas3d, Cas5d, Cas6d, Cas7d, Cas10d, and a crRNA (pg. 12; see FIG. 2). Osakabe teaches that the method can be utilized to alter gene expression via transcriptional activation or inactivation ([0085]).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method rendered obvious by claims 1 and 3 of US Patent No. 12,012,596 in view of Lin such that the method was utilized to alter gene expression via transcriptional activation or inactivation, as described by Osakabe. A person of ordinary skill in the art would have been motivated to do so in order to control gene expression of a gene of interest. A person of ordinary skill in the art would have had a reasonable expectation of success because both Osakabe and claims 1 and 3 of US Patent No. 12,012,596 in view of Lin are drawn towards the use of CRZISPR type I-D systems that can target and edit nucleic acids of interest.
Regarding claims 5 and 29, claims 1 and 3 of US Patent No. 12,012,596 in view of Lin does not teach or suggest that the method can be performed in a eukaryotic cell (Claims 5 and 29). Regarding claim 23, claims 1 and 3 of US Patent No. 12,012,596 in view of Lin does not teach or suggest that the method can be performed in a plant cell (Claim 23). Regarding claim 24, claims 1 and 3 of US Patent No. 12,012,596 in view of Lin does not teach or suggest that the method can be performed in a non-human animal cell (Claim 24). Regarding claims 25-26, claims 1 and 3 of US Patent No. 12,012,596 in view of Lin does not teach or suggest that the method can be utilized to bring the system into contact with an isolated nucleic acid (Claims 25-26).
However, as discussed above, one of ordinary skill in the art would have considered the teachings of Osakabe.
Osakabe teaches that the method can be performed in a eukaryotic cell ([0015]). Osakabe teaches that the method may be performed in a plant cell ([0015]). Osakabe teaches that the method may be performed in a non-human animal cell ([0015]). Osakabe teaches that the method may be performed in vitro (i.e., the target nucleotide sequence may be isolated) ([0026]).
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 cell rendered obvious by claims 1 and 3 of US Patent No. 12,012,596 in view of Lin for a eukaryotic cell, a plant cell, a non-human animal cell, or an in vitro environment, as described by Osakabe. A person of ordinary skill in the art would have had a reasonable expectation of success because both Osakabe and claims 1 and 3 of US Patent No. 12,012,596 in view of Lin teach the use of CZRIPR type I-D systems that can be utilized in target cells or environments of interest.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KYLE T REGA whose telephone number is (571)272-2073. The examiner can normally be reached M-R 8:30-4:30, every other F 8:30-4:30 (EDT/EST).
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Neil Hammell can be reached at 571-270-5919. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KYLE T REGA/Examiner, Art Unit 1636
/NEIL P HAMMELL/Supervisory Patent Examiner, Art Unit 1636