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 .
Applicants file a Preliminary Amendment on November 27, 2023, in which they canceled claims 3, 6-7, 9-10, 12, 17, 19, 24-27, 30, 33, and 35, and amended claims 2, 4-5, 8, 11, 13-16, 18, 22-23, 28-29, 32, and 36-37.
Election/Restrictions
Applicant’s election without traverse of Group I (claims 1-2, 4-5, 8, 11, 13-16, 18, 20-23, 28-29, and 36) in the reply filed on May 4, 2026 is acknowledged.
Claims 31-32, 34, and 37-38 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 May 4, 2026.
In addition, Applicants elect species E563R. Applicants further submit that the amino acids K and H are positively charged, as is R. Applicants’ assertion is persuasive, and E563R, E563K, and E563R are examined. It is also noted that these three species were not found in the search. Therefore, the search for additional amino acid species is expanded.
Applicants also amended claims 1-2, 4-5, 8, 11, 13-14, 16, 18, 20-22, 23, 28-29, and withdrawn claim 32. Claims 1-2, 4-5, 8, 11, 13-16, 18, 20-23, 28-29, and 36 are under examination.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55. However, certified translations have not yet been filed.
Information Disclosure Statement
The Information Disclosure Statements filed June 24, 2024; January 9, 2025; and May 4, 2026 have been considered.
Specification
The use of the terms TALEN and page 1, line 22; PYMOL at page 32, line 16; page 39, line 7; page 42, line 28; page 114, line 2; page 117, line 4; page 119, line 2; page 122, line 13, and page 125, line 7; CHIMERAX at page 32, line 16; page 39, line 7; page 42, line 29; page 114, line 2; page 117, line 4; page 119, line 2; page 122, line 13, and page 125, line 7; LIPOFECTAMINE at page 114, line 12; page 117, line 13; page 123, line 9; page 125, line 17; page 128, line 17; page 134, line 2; page 136, line 9; page 139, line 17; page 142, line 10; page 144, line 10; and page 147, line 12; MOFLO at page 114, line 16; page 117, line 18; page 119, line 23; page 123, line 13; page 126, line 1; and page 128, line 1; CRISPRESSO at page 114, line 24; page 117, line 26; page 119, line 3; page 123, line 24; page 126, line 9; page 128, line 3; and page 130, line 27; SEPHAROSE at page 131, line 24; DNA CLEAN & CONCENTRATOR at page 132, lines 13-14; COVARIS at page 134, line 14 and page 147, line 21; and QUBIT at page 134, line 13 and page 147, line 21; which are trade names or marks used in commerce, has been noted in this application. The terms should be accompanied by the generic terminology; furthermore the terms should be capitalized wherever they appear or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Rejections - 35 USC § 112
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 23 and 28 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.
At claim 23, lines 2 and 8, the phrase “functional derivative” is unclear because it does not set forth any structure or sequence that must be maintained in order to be considered a functional derivative.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c).
In the present instance, claim 23 recites the broad recitation “the Cas12i effector protein,” and the claim also recites that “the Cas12i effector protein is capable of inducing double-strand breaks or single-strand breaks in DNA molecules” and “the engineered Cas12i nuclease or a functional derivative thereof is an enzyme inactive mutant.”
In the present instance, claim 23 recites the broad recitation “a functional domain,” and the claim also recites “preferably, the functional domain is one or more selected from the group consisting of: translation initiation domain . . . and nuclease domain,” which is the narrower statement of the range/limitation. The claims are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claim 28 depends from claim 23 and is therefore included in these rejections.
At claim 28, lines 2 and 4, the phrase “functional derivative” is unclear because it does not set forth any structure or sequence that must be maintained in order to be considered a functional derivative.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 8, 22-23, 28-29, and 36 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Cheng et al. (U.S. Patent Application Publication No. 2020/0063126, published February 27, 2020, and cited in the Information Disclosure Statement filed June 24, 2024).
Regarding claim 1, Cheng discloses Type V-I CRISPR nucleases, which are also referred to as CRISPR-Cas12i (paragraph [0012]. Cheng discloses the sequence of the Cas12i that includes a replacement of an amino acid in the RuvC domain, which interacts with a single-stranded DNA substrate, and which has a sequence that has 99.5% identity to the sequences of the instantly claimed Cas12i (SEQ ID NO: 5) (Appendix 1, SEQ ID NOS: 2-24).
Regarding claim 8, Cheng discloses that amino acid 418 has the leucine replaced with an alanine (SEQ ID NO: 5) (Appendix 1, SEQ ID NOS: 2-24).
Regarding claim 22, Cheng discloses the sequence of the Cas12i that includes a replacement of an amino acid in the RuvC domain, which interacts with a single-stranded DNA substrate, and which has a sequence that has 99.5% identity to the sequences of the instantly claimed Cas12i (SEQ ID NO: 5) (Appendix 1, SEQ ID NOS: 2-24).
Regarding claim 23, Cheng discloses that the Cas12i can be inactive, can induce double- or single-strand breaks (paragraphs [0349]-[0350] and [0393]). Cheng discloses that the Cas12i can include a heterologous functional domain, including specific nucleobase modification or a nuclease domain such as FokI (paragraphs [0269] and [0391]).
Regarding claim 28, Cheng discloses that the Cas12i can be a split enzyme, which can associate with each other to form a functional enzyme and form a complex with a guide RNA that can bind to a target site (paragraphs [0207]-[0211]).
Regarding claim 29, Cheng discloses a system comprising a guide RNA and the Cas12i (paragraph [0012]).
Regarding claim 36, Cheng discloses a composition and kit comprising the Cas12i (paragraphs [0322]-[0323]).
Cheng discloses each and every limitation of claims 1, 8, 22-23, 28-29, and 36. Therefore, Cheng anticipates claims 1, 8, 22-23, 28-29, and 36,
Allowable Subject Matter
Claims 2, 4-5, 11, 13-16, 18, and 20-21 are 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. The prior art fails to disclose or suggest Cas12i nucleases that have amino acid substitutions at the claimed positions, based on SEQ ID NO: 1.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Rusk (16 Nature Methods 215 (2019)) discloses that Type V CRISPR-Cas elements were discovered to be one of three major branches (column 1, fourth paragraph). Rusk discloses that Cas12i belongs to the second branch (column 1, fourth paragraph). Rusk discloses that Cas12i does not require a tracrRNA for single-strand DNA cleavage or for nicking the DNA strand (column 2 first full paragraph).
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NANCY J LEITH whose telephone number is (313)446-4874. The examiner can normally be reached Monday - Thursday 8:00 AM - 6:30 PM.
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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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NANCY J. LEITH
Primary Examiner
Art Unit 1636
/NANCY J LEITH/Primary Examiner, Art Unit 1636
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