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 response of 04/20/2026, including a substitute specification and replacement drawings, has been received and entered into the application file.
Claims 1, 2, 6-10, 15, and 17 were amended in the claim set filed 04/20/2026.
Claims 18 and 19 were added in the claim set filed 04/20/2026.
Accordingly, claims 1-19 are pending and under consideration.
Election/Restrictions
Applicant's previous election with traverse of Group I (claims 1-16) with a species election of Blackjack-SpCas9 (SEQ ID NO: 13) in the reply filed on 08/26/2025 is acknowledged. The traversal was on the grounds that the cited art in the restriction requirement dated 06/26/2025 (CA 3069296 A1; hereinafter Kim; previously cited) does not teach or suggest all the elements of claim 1. After searching the patent and non-patent literature for the elected invention and species, this was found persuasive. Accordingly, the restriction requirement dated 06/26/2025 was previously withdrawn, as acknowledged by Applicant in the reply filed 04/20/2026.
Status of Prior Objections/Rejections
RE: Drawings
The drawings were previously objected to for various informalities.
The replacement drawings filed 04/20/2026 have obviated the basis of the objections of record. Therefore, the objections of record are hereby withdrawn.
However, new grounds of objection are set forth below.
However, further review of the application file has necessitated new grounds of objection, which are set forth below.
RE: Nucleotide and/or Amino Acid Sequence Disclosures
It was previously indicated that the Incorporation by Reference paragraph was missing or incomplete and further that sequences appeared in the drawings and specification without being properly identified with sequence identifiers.
The substitute specification filed 04/20/2026 includes the required Incorporation by Reference paragraph, thereby obviating the basis of the sequence compliance issue previously set forth.
The replacement drawings and substitute specification filed 04/20/2026 properly identify all sequences with their respective sequence identifiers, thereby obviating the basis of the sequence compliance issues previously set forth.
The instant drawings and specification are in sequence compliance.
RE: Specification
The disclosure was previously objected to for various informalities.
The substitute specification filed 04/20/2026 has obviated the basis of the objections of record. The Examiner acknowledges Applicant’s arguments regarding the configuration of Table 8, and all objections of record are hereby withdrawn.
RE: Claim Objections
Claims 1, 2, 6-10, 12, and 15-17 were previously objected to for minor informalities.
The amendments to the instant claims, have obviated the basis of most, but not all, of the objections of record.
Those objections not repeated below are hereby withdrawn.
RE: Claim Rejections - 35 USC § 112(a)
►Claims 1 and 11-17 were previously rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement.
The amendments to the instant claim set have obviated the basis of the rejection of record. Accordingly, the rejection of record is hereby withdrawn.
►Claims 9 and 10 were previously rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The amendments to the instant claim set have obviated the basis of the rejection of record. Accordingly, the rejection of record is hereby withdrawn.
RE: Claim Rejections - 35 USC § 112(b)
Claims 1, 2, 5, 7-9, 12, and 15-17 were previously rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 1, 2, 5, 7-9, 12, and 15-17 were previously rejected for reciting the term “preferably,” thereby rendering the scope of the claim unclear.
Applicant has deleted some, but not all, recitations of the term “preferably” in the amended claim set filed 04/20/2026. Applicant has further traversed the rejection of record, asserting that the MPEP does not prohibit the use of relative or preference language per se, but rather the test is whether the claim “reasonably apprises those skilled in the art of the scope.” Nautilus, Inc. v. Biosig Instruments, Inc. 572 U.S. 898 (2014). Applicant further asserts that the claim language covers the broader embodiment, while the preferred embodiments are all recited more narrowly, which does not obscure the scope of the instant claim language.
In response, this is not found persuasive. While the use of “preferably” in the instant claim set may essentially be interpreted as “optionally” per Applicant’s arguments, which is consistent with a reading of the instant claim set, the term “preferably” is not redefined to mean “optionally” in the instant specification. Accordingly, it must be given its plain meaning, which is that “preferably” is used to indicate what is wanted or preferred (per Merriam-Webster entry “preferably”), not what is required. Therefore, the scope of any claim reciting “preferably” is obscured, meaning one of ordinary skill in the art would not be reasonably apprised of the subject matter claimed therein.
Accordingly, while Applicant’s amendments have obviated the basis of the rejection of some claims, this is not true of all claims. Those rejections not repeated below are hereby withdrawn.
New/Maintained Grounds of Objection/Rejection
Drawings
The drawings are objected to because:
37 CFR 1.84 (u)(1) states “View numbers must be preceded by the abbreviation "FIG."”
In the instant case, the view numbers for all Figures are preceded by the word "Figure" instead of the abbreviation "FIG.". It would be remedial to precede each drawing with the abbreviation “FIG.” in place of “Figure.”.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Objections
Claims 3-6, 9, 10, 12, 16, and 17 are objected to because of the following informalities:
With regard to claim 3, the recitation of “SEQ ID NOs 6 to 23” lacks a colon preceding the recited SEQ ID NOs. It would be remedial to amend the instant claim to recite “SEQ ID NOs: 6 to 23” (bolded and underlined emphasis added).
With regard to claim 4, the recitation of “SEQ ID NO. 13” is not consistent with the conventional recitation of sequence identifiers, which utilizes a colon preceding the recited SEQ ID NOs. It would be remedial to amend the instant claim to recite “SEQ ID NO: 13” (bolded and underlined emphasis added).
With regard to claim 5, the instant claim structure does not comport with standard grammatical and/or linguistic conventions. The recitation of “7 to 11 amino acids or 8 to 10 amino acids or highly preferably 9 amino acids” lacks commas properly separating clauses within the instant claim language. It would be remedial to amend the instant claim to include said commas, for example “7 to 11 amino acids, or 8 to 10 amino acids, or highly preferably 9 amino acids” (bolded and underlined emphasis added), thereby comporting with standard grammatical and/or linguistic conventions.
With regard to claim 6, the instant claim structure does not comport with standard grammatical and/or linguistic conventions. The recitation of “the variant Cas9 protein according to claim 1, said mutation also comprising an insertion to replace the segment deleted wherein…” lacks a comma preceding the “wherein” clause. It would be remedial to amend the instant claim to include said comma, for example “the variant Cas9 protein according to claim 1, said mutation also comprising an insertion to replace the segment deleted, wherein…” (bolded and underlined emphasis added), thereby comporting with standard grammatical and/or linguistic conventions. Furthermore, the recitation of “said insertion having a length of 1 to 6 amino acid(s) and comprises amino acids which are different from acidic and aromatic amino acids…” (bolded emphasis added) is not structurally consistent internally. The bolded “comprises” should recite “comprising” for purposes of internal consistency.
Claim 9 includes numerous grammatical and/or typographical errors. For example, “intalics” should be spelled “italics” and should not be followed by a lone parenthesis. Furthermore, there are numerous punctuation marks missing from the instant claim. As previously set forth, the absence of a coordinating conjunction separating the recited preferred SEQ ID NOs substantially complicates the interpretation of instant claim 9. Finally, the instant claim still recites UniProt entry identifier(s). As previously set forth, incorporation by reference of essential material is only permitted by way of an incorporation by reference to a U.S. patent or U.S. patent application publication, which patent or patent application itself does not incorporate such essential material by reference. In the instant case, incorporation by reference of an electronic database is subject to change over time is improper, and the claims should only refer to the instant SEQ ID NOs. It would be remedial to amend instant claim 9 such that it comports with standard grammatical and/or linguistic conventions and such that all UniProt identifier(s) is/are appropriately removed.
With regard to claim 10, the recitation of “90% sequence identity to the amino acid sequence of (SEQ ID NO: 2)” includes parentheses that are unnecessary and improper. It would be remedial to remove the parentheses encompassing SEQ ID NO: 2. Additionally, the recitation of “selected from the following group consisting of SEQ ID NOs 6 to 23” lacks a colon preceding the recited SEQ ID NOs. It would be remedial to amend the instant claim to recite “SEQ ID NOs: 6 to 23” (bolded and underlined emphasis added).
With regard to claim 12, the recitation of “a single guide RNA (sgRNA)” is not internally consistent, as “crRNA” is recited in the same claim without any definition of said acronym. These acronyms are both defined at instant claim 1. Thus, there is no need to define these acronyms again. For purposes of internal consistency, it would be remedial to recite “an sgRNA” in place of “a single guide RNA (sgRNA)” at instant claim 12 (bolded and underlined emphasis added).
With regard to claim 16, the recitation of “single guide RNA” intermixed with “sgRNA” in the same claim lacks internal consistency. As set forth above, sgRNA is defined at instant claim 1 (along with crRNA). Thus, there is no need to define these acronyms again. For purposes of internal consistency, it would be remedial to recite “sgRNA” in place of “single guide RNA” throughout instant claim 16.
With regard to claim 17, the recitation of “single guide RNA (sgRNA)” is not internally consistent, as “crRNA” is recited in the same claim without any definition of said acronym. These acronyms are both defined at instant claim 1. Thus, there is no need to define these acronyms again. For purposes of internal consistency, it would be remedial to recite “sgRNA” in place of “a single guide RNA (sgRNA)” at instant claim 17.
Appropriate correction is required.
The Examiner notes that the instant claim set requires substantial grammatical and/or typographical revision to be in condition for allowance. While those errors that most impact interpretation have been noted and set forth above, this is not an exhaustive list of all minor grammatical and/or typographical errors. It would be remedial to carefully review the instant claim set to correct such errors.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 5, 7-9, 12, and 15-18 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding claims 5, 7-9, 12, and 15-17, the phrase "preferably" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Regarding claim 18, claim 18 depends from claim 9 and does not resolve the basis of the indefiniteness rejection set forth above. Thus, claim 18 is also rejected as being indefinite for the reasons set forth above.
Allowable Subject Matter
Claims 1, 2, 11, 13, 14, and 19 are allowed.
The following is a statement of reasons for the indication of allowable subject matter:
While Cas9 and variants thereof (including high-fidelity variants) are well-known in the art, as set forth in the instant specification and supported by a search of both the patent and non-patent literature, the instantly-claimed Cas9 variant comprising a mutation in the surface loop as set forth at instant claim 1 does not appear to have been known in the field as of the effective filing date, nor does the state of the art as of the effective filing date provide sufficient motivation to arrive at the instant invention. While Slaymaker et al., 2016 (of record) does disclose that the RuvC domain (which comprises the region of mutated amino acid residues set forth in the instant application per UniProt entry Q99ZW2) is implicated in stabilizing the nontarget strand of the target DNA and is thus a viable target to alter in order to require more stringent Watson-Crick base pairing between the RNA guide and the target DNA strand (page 84, text column 2, paragraph 2), they do not disclose the instantly claimed mutation. Additionally, CA 3069296 A1 (hereinafter Kim; of record) discloses the deletion of one or more amino acids in region 2-3 of SpCas9 to improve target specificity (page 12, lines 16-19; page 94, lines 9-11), which completely encompasses the instantly claimed range of 6-12 amino acids and must necessarily produce a Cas9 with the instantly claimed structure and function (see MPEP § 2114 and § 2173.05(g)), as set forth in the restriction requirement dated 06/26/2025. However, as Applicant noted in the reply dated 08/26/2025, this disclosure constitutes “a laundry list of possible mutated amino acids”; furthermore, Kim does not motivate the deletion of 6-12 amino acids specifically, as instantly claimed.
In summary, it does not appear that a person having ordinary skill in the art would have been sufficiently motivated by what was known in the field at the time of the effective filing date of the claimed invention to alter a wild-type Cas9 to arrive at the instantly claimed variant Cas9.
Conclusion
Claims 1, 2, 11, 13, 14, and 19 are allowed.
Claims 5, 7-9, 12, and 15-18 are rejected.
Claims 3-6, 9, 10, 12, 16, and 17 are objected to.
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 Sarah E Allen whose telephone number is (571)272-0408. The examiner can normally be reached M-Th 8-5, F 8-12.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jennifer Dunston can be reached at 571-272-2916. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SARAH E ALLEN/Examiner, Art Unit 1637
/J. E. ANGELL/Primary Examiner, Art Unit 1637
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