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 .
Application Status
This action is written in response to applicant’s correspondence received 20 April 2026. Claims 1-8, 10-11, 14-16, 20, and 22-30 are currently pending. Claims 7-8, 10-11, 14-16, 20, and 30 are withdrawn from prosecution as being drawn to non-elected subject matter. Accordingly, claims 1-6 and 22-29 are examined herein. The restriction requirement mailed 10 October 2025 is still deemed proper. Applicant's elected Group I without traverse in the reply filed 8 December 2025.
Any rejection or objection not reiterated herein has been overcome by amendment.
Applicant' s amendments have been thoroughly reviewed, but are not persuasive to place the
claims in condition for allowance for the reasons that follow.
Claim Interpretation
Regarding claims 1, 22, and 25, it is noted that the instant specification teaches that “Cas10d used in the present invention may be a polypeptide containing at least the N-terminal HD domain. For example, the Cas10d may be the full-length Cas10d protein, a polypeptide containing a region extending from the N-terminal HD domain to one or more C-terminal α-helix regions of Cas10d, or a polypeptide containing the N- terminal HD domain of Cas10d and lacking one or more C-terminal α-helix regions of Cas10d. The Cas10d may lack all of the C- terminal α-helix regions. As used herein, the term ‘Cas10d’ includes the full-length Cas10d polypeptide and Cas10d fragments containing the N-terminal HD domain as described above” (Instant specification; [0023]).
Therefore, under the broadest reasonable interpretation of the claims, part (i) of claims 1, 22, and 25 are interpreted as being directed towards CRISPR type I-D proteins Cas5d, Cas6d, Cas7d, and a Cas10d fragment comprising only an N-terminal HD domain.
Applicable Prior Art
Additionally, it is noted that the instant specification teaches that background art applicable to the instant application includes the subsequently referenced McBride reference in this Office Action ([0004]-[0011]). Further, the IDS filed 24 May 2023 teaches that the McBride reference was first available online 11/27/2020.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code in paragraph [0011]. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Claim Rejections - 35 USC § 112
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 4 and 28 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. This is a new rejection necessitated by amendment.
Regarding claims 4 and 28, the claims recite that the C-terminal partial sequence of Cas10d comprises an amino acid sequence consisting of 100-400 amino acids (see Claims 4 and 28). However, claim 1 (i.e., the claim from which both claims 4 and 28 ultimately depend) already recites that the C-terminal partial sequence of Cas10d contains 135-170 amino acids (see Claim 1). Therefore, claims 4 and 28 fail to further limit the subject matter of claim 1 because claim 1 already defines the length of the C-terminal partial sequence as falling within the broader ranges recited in claims 4 and 28.
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.
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 22-29 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 McBride ("Diverse CRISPR-Cas complexes require independent translation of small and large subunits from a single gene." Molecular cell 80.6 (2020): 971-979). This is a new rejection necessitated by amendment.
Regarding claims 1, 22, and 25, Osakabe is drawn towards a method for targeting a target nucleotide sequence (Abstract). Osakabe teaches a method for altering a target nucleotide sequence on the genomic DNA of a eukaryotic cell, the method comprising introducing into the eukaryotic cell an expression vector encoding (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 Claims 1, 6, and 8). 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 or in vivo (i.e., the target nucleotide sequence may be isolated and present within a target cell) ([0026]).
Osakabe does not teach or suggest the use of a polypeptide consisting of a C-terminal partial sequence of Cas10d that does not contain the N-terminal HD domain of Cas10d and contains 135-170 amino acids from the C-terminus of the full-length amino acid sequence (Claims 1, 22, and 25).
McBride is drawn towards a study concerned with the characterization of a previously uncharacterized type I-D CRISPR system (Abstract). McBride teaches the co-expression of Cas3′, Cas10d, Cas7d, Cas5d, and Cas6d from Synechocystis with the first repeat-spacer-repeat of the associated CRISPR array in E. coli (pg. 972; Figure 1A). McBride teaches that the C-terminus of Cas10d, a subunit referred to as “Cas11d”, results from an internal translational initiation site present within Cas10d (pg. 973; see Figure 2A). McBride teaches that Cas11d maps to residues 830-975 of Cas10d (i.e., Cas11d is 146 amino acids in length) (pg. e4). McBride teaches that a Cas10d construct lacking the Cas11d subunit, termed “ΔCas11d”, (i.e., a Cas10d N-terminal fragment reading on the claimed Cas10d protein as discussed above in the “Claim Interpretation”) only showed DNA binding comparable to the wildtype Cas10d when a complementation with Cas11d expressed from a separate plasmid restored the protein constituents of the wild-type complex (pg. 973).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have substituted the nucleic acid encoding the Cas10d of Osakabe for the ΔCas11d construct of McBride (i.e., a construct that comprises nucleic acids encoding the claimed Cas10d protein as described above), alongside the expression of a separate plasmid expressing Cas11d because it would have merely amounted to a simple substitution of one known element for another to obtain predictable results. Because McBride teaches that the Cas11d subunit can be expressed from a second nucleic acid and associate with the Cas10d protein lacking the Cas11d subunit in order to restore wildtype binding affinities of the CRISPR system, one would have expected that utilizing the nucleic acids encoding the ΔCas11d protein and Cas11d protein to have behaved identically to the Cas10d protein present within the method of Osakabe when expressed. Additionally, because both references teach the use of nucleic acids encoding the Cas10d proteins, one would have expected the substitution to have predictably resulted in the successful expression of the ΔCas11d protein and Cas11d protein, wherein the expression results in wildtype Cas10d activity.
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, McBride teaches that the Cas11d subunit is 146 amino acids in length (pg. e4).
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 McBride ("Diverse CRISPR-Cas complexes require independent translation of small and large subunits from a single gene." Molecular cell 80.6 (2020): 971-979). This is a new rejection necessitated by amendment.
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 consisting of a C-terminal partial sequence of Cas10d that does not contain the N-terminal HD domain of Cas10d and contains 135-170 amino acids from the C-terminus of the full-length amino acid sequence (Claims 1, 22, and 25).
The applicable teachings of McBride are discussed above as applied to claims 1, 22, and 25.
Therefore, it would have been obvious for the same reasons as discussed above in the currently pending 35 USC 103 rejections of record of claims 1-6 and 22-29 to have substituted the nucleic acid encoding the Cas10d of Osakabe for the ΔCas11d construct of McBride (i.e., a construct that comprises nucleic acids encoding the claimed Cas10d protein as described above), alongside the expression of a separate plasmid expressing Cas11d.
Regarding claims 2 and 26, patented claim 1 claim the use of a Cas3d protein.
Regarding claims 4 and 28, McBride teaches that the Cas11d subunit is 146 amino acids in length (pg. e4).
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 McBride ("Diverse CRISPR-Cas complexes require independent translation of small and large subunits from a single gene." Molecular cell 80.6 (2020): 971-979) as described above, further in view of Osakabe (PG Pub No: CA 3,073,372, published 19 February 2019). This is a new rejection necessitated by amendment.
Regarding claims 3, 5, 23-27, and 29, claims 1 and 3 of US Patent No. 12,012,596 in view of McBride 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 McBride does not teach or suggest that the method can be utilized to alter gene expression via transcriptional activation or inactivation (Claims 3 and 27).
The applicable teachings of Osakabe are discussed above as applied to claims 1-6 and 22-29.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modify the method rendered obvious by claims 1 and 3 of US Patent No. 12,012,596 in view of McBride such that the method was utilized to alter gene expression via transcriptional activation or inactivation, as described by Osakabe, because it would have merely amounted to a combination of prior art elements according to known methods to yield predictable results. Because both the patented claims and Osakabe teach the use of CRISPR type I-D systems for the targeting and editing of nucleic acids of interest within cells, one would have expected modifying the method of the patented claims such that it transcriptionally activated or inactivated a target gene would have predictably resulted in the modulation of the genes expression. And because Osakabe teaches that the system can be used to control gene expression of a gene of interest, one would have been motivated to have modified the patented method to have done so.
Regarding claims 5 and 29, claims 1 and 3 of US Patent No. 12,012,596 in view of McBride 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 McBride 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 McBride 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 McBride 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).
The applicable teachings of Osakabe are discussed above as applied to claims 1-6 and 22-29.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have substituted the cell rendered obvious by claims 1 and 3 of US Patent No. 12,012,596 in view of McBride for a eukaryotic cell, a plant cell, a non-human animal cell, or an in vitro environment, as described by Osakabe, because it would have merely amounted to simple substitution of one known element for another to obtain predictable results. Because both Osakabe and the patented claims teach that the type I-D system can be used in different environments and cells, one would have expected modifying the patented method such that the system was introduced into the claimed environments to have successfully resulted in the editing of a target nucleic acid within the environments.
Response to Arguments
Applicant’s arguments with respect to the previously utilized Lin reference in the previous rejection of claim(s) 1-6 and 22-29 have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Insofar as Applicant’s arguments pertain to the newly recited 35 USC 103 and double patenting rejections of record, Applicant alleges that the references do not teach the expression of a Cas10d protein and a polypeptide consisting of a C-terminal, partial sequence of type I-D Cas10d for targeting a target nucleotide sequence (Remarks; pg. 2-3).
This argument is not found persuasive because, as discussed above, the instant specification teaches that “Cas10d used in the present invention may be a polypeptide containing at least the N-terminal HD domain. For example, the Cas10d may be the full-length Cas10d protein, a polypeptide containing a region extending from the N-terminal HD domain to one or more C-terminal α-helix regions of Cas10d, or a polypeptide containing the N- terminal HD domain of Cas10d and lacking one or more C-terminal α-helix regions of Cas10d. The Cas10d may lack all of the C- terminal α-helix regions. As used herein, the term ‘Cas10d’ includes the full-length Cas10d polypeptide and Cas10d fragments containing the N-terminal HD domain as described above” (Instant specification; [0023]).
Therefore, under the broadest reasonable interpretation of the claims, part (i) of claims 1 and 22 are interpreted as being directed towards CRISPR type I-D proteins Cas5d, Cas6d, Cas7d, and a Cas10d fragment comprising only an N-terminal HD domain as rendered obvious by the combination of Osakabe and McBride.
Applicant alleges that the instant specification provides the unexpected result of the C-terminal partial sequence of Cas10d alongside the Cas10d protein resulted in a 2.5 fold increase in genome editing activity compared to the genome editing activity of Cas3d, Cas5d, Cas6d, Cas7d, and Cas10d alone (Remarks; pg. 5).
This argument is not found persuasive because McBride teaches that a Cas10d construct lacking the Cas11d subunit, termed “ΔCas11d”, (i.e., a Cas10d N-terminal fragment reading on the claimed Cas10d protein as discussed above in the “Claim Interpretation”) only showed DNA binding comparable to the wildtype Cas10d when a complementation with Cas11d expressed from a separate plasmid restored the protein constituents of the wild-type complex (pg. 973). Therefore, one of ordinary skill in the art would have expected that the expression of the C-terminal partial sequence to result in an increased in genome editing because McBride teaches that the C-terminal partial sequence is required by the ΔCas11d construct in order to bind to DNA.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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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/KYLE T REGA/Examiner, Art Unit 1636
/NEIL P HAMMELL/Supervisory Patent Examiner, Art Unit 1636
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