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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on December 2, 2025 has been entered.
Application Status
Applicant’s remarks and amendments to the claims filed December 2, 2025 are acknowledged. Claims 8, 22, 26, 28, 42, 52, 59, and 70 were amended, and claims 86-87 were introduced. Claims 1, 3-5, 8-9, 12, 14, 17, 19-20, 22, 26, 28, 30, 42, 45, 48-49, 52, 59, 64-65, 70, and 86-87 are pending and under examination hereinafter.
Withdrawn Rejections
Applicant’s amendments to the claims resolve the objections to the claims raised in the prior action. The amendments also overcome the grounds for the § 112(b) rejections raised in the prior action. The aforementioned rejections are withdrawn, accordingly.
Applicant’s remarks and amendments to the claims have been thoroughly reviewed, but are not found persuasive to place the claims in condition for allowance for the reasons that follow. Any objection or rejection not reiterated herein has been overcome by amendment.
Specification
The specification is objected to because of the following informalities:
The specification contains embedded hyperlinks and/or other form of browser-executable code. See at least paragraphs [00165], [00222]-[00224], [00599]-[00600], [01074], and other paragraphs throughout the specification. Applicant is required to delete the embedded hyperlinks 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.
Appropriate correction is required.
Claim Objections
Claims 26, 59, and 87 are objected to because of the following informalities:
Claim 26 recites “wherein modifying of the one or more target sequences of interest comprises an insertion of deletion of one or more nucleotides,” which should be amended to recite “wherein modifying [[of]] the one or more target sequences of interest comprises an insertion or[[of]] deletion of one or more nucleotides” to improve the grammar of the claim.
Claim 59 recites “said guide sequence.” Although no such “guide sequence” is previously recited in the claim, it is reasonably clear that this term refers to the previously recited “guide molecule.” As such, it would be preferable to amend the claim to recite “said guide molecule
Claim 59 recites “(A)… or catalytic domain thereof thereof,” and “(B)… or catalytic domain thereof thereof,” each of which should be amended to strike the duplicated word.
Claim 87 recites “wherein modifying of the one or more target sequences of interest comprises increasing or decreasing expression of the one or more target sequences of interest,” which should be amended to recite “wherein modifying [[of]] the one or more target sequences of interest comprises increasing or decreasing expression of the one or more target sequences of interest” to improve the grammar of the claim.
Appropriate correction is required.
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 28 and 87 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. The following rejections are new and necessitated by Applicant’s amendments to the claims.
The methods of claims 28 and 87 depend from the method of claim 26, which requires a Cas12b effector protein, and wherein “modifying [] the one or more target sequences of interest comprises an insertion [or] deletion of one or more nucleotides.” Claims 28 and 87 recite distinct “modifying” outcomes, which are linked to the additional structural elements recited in each claim. Claim 28 requires that the Cas12b effector protein be coupled to an engineered adenosine deaminase, such that “modifying the one or more target sequences of interest comprises deaminating one or more nucleotides in the one or more target sequences of interest.” Claim 87 requires that the Cas12b effector protein be coupled to a transcriptional activator or repressor, such that “modifying [] the one or more target sequences of interest comprises increasing or decreasing expression of the one or more target sequences of interest.”
The phrasing of the distinct “modifying” outcomes of the dependent claims, i.e., phrasing which is substantially identical to the phrasing in claim 26, makes it unclear whether claims 28 and 87 still require the outcome of “insertion [or] deletion of one or more nucleotides,” or whether the claims intend to replace the previously recited outcome with the later recited outcome which corresponds to the structural elements in the claim (i.e., the engineered adenosine deaminase, and the transcriptional activator or repressor). These interpretations lead to different, mutually exclusive claim scopes, which renders the claims indefinite.
Response to Remarks - § 112(b)
Applicant’s remarks regarding the § 112(b) rejections raised in the prior action have been reviewed. The remarks are moot because the previous rejections have been withdrawn, and none of Applicant’s remarks are relevant to the new rejections above, which are necessitated by Applicant’s amendments to the claims.
Claim Rejections - 35 USC § 112(a) – Written Description
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claim 59 is 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. This is a new matter rejection necessitated by Applicant’s amendments to the claims.
MPEP 608.04(a) states that “If the new matter has been entered into the claims or affects the scope of the claims, the claims affected should be rejected under 35 U.S.C. 112(a)… on the ground that it recites elements without support in the original disclosure.”
Claim 59 has been amended to recite “wherein (A) said adenine or cytosine is outside said target sequence that forms said oligonucleotide duplex, wherein said adenosine deaminase, cytidine deaminase, or catalytic domain thereof [] deaminates said adenine or cytosine outside said oligonucleotide duplex.” Applicant’s remarks do not indicate where support for the amendments to claim 59 may be found in the original disclosure.
A thorough review of the disclosure uncovered written support for a cytosine outside the target sequence that forms said oligonucleotide duplex, wherein a cytidine deaminase or catalytic domain thereof deaminates the cytosine ([00030]; [00620]; [00919]; “59.,” pg. 577). However, no explicit or implicit written support was found for an adenine outside the target sequence that forms said oligonucleotide duplex, or an adenosine deaminase which deaminates any nucleotide outside of the target sequence. The newly introduced limitations in “(A)” which refer to adenine and an adenosine deaminase fail to comply with the written description requirement.
Allowable Subject Matter
As stated in paragraph 20 of the prior action, a thorough review of the prior art failed to uncover any teaching or suggestion of a Cas12b effector protein at least 95% identical to SEQ ID NO: 519 wherein the Cas12b effector protein comprises one or more mutations at amino acid positions K8456, S893, and E837 relative to SEQ ID NO: 519. Accordingly, the instantly claimed Cas12b effector protein, and systems and methods comprising the Cas12b effector protein are free of the prior art applied and considered during examination.
Conclusion
Claims 1, 3-5, 8-9, 12, 14, 17, 19-20, 22, 30, 42, 45, 48-49, 52, 64-65, 70, and 86 are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JENNA L PERSONS whose telephone number is (703)756-1334. The examiner can normally be reached M-F: 9-5pm.
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/JENNA L PERSONS/Examiner, Art Unit 1637
/Soren Harward/Primary Examiner, TC 1600