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 amendment of claims 1, 14, 17, in the paper of 9/4/2025, is acknowledged. Applicants' arguments filed on 9/4/2025, have been fully considered and are deemed to be persuasive to overcome some of the rejections previously applied. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. Claims 1-5, 7, 8, 11, 12, 14, 16-18, 82, 83 and 88-92 are pending and at issue.
Election/Restrictions
Applicant's election without traverse of the following species:
Species Group 1: (i) (a) a first polynucleotide molecule encoding a Cas protein and an N-terminal fragment of a dimerization protein; and (b) a second polynucleotide molecule encoding a C-terminal fragment of a dimerization protein and a reverse
Species Group 2: Cas nickase.
Species Group 3: 840 substitution position.
Species Group 4: H840N
Species Group 5: M-MLV reverse transcriptase.
Species Group 6: (a) the split point is localized at any amino acid between
position 564 and 584, and the N-terminal fragment of Cas9 nickase comprises nucleotides from position 1 of the Cas9 nickase to the split point and the C- terminal fragment of Cas9 nickase comprises nucleotides from the split point to
position 1371 of the Cas9 nickase
. Species Group 7: (a) the split point is localized at any amino acid between
position 703 and 723, and the N-terminal fragment of Cas9 nickase comprises nucleotides from position 1 of the Cas9 nickase to the split point and the C- terminal fragment of Cas9 nickase comprises nucleotides from the split point to
position 1371 of the Cas9 nickase
.
in the paper of 10/15/2024, is acknowledged.
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.
Claim 1-5, 7, 8, 11, 12, 14, 16-18, 82, 83 and 88-92 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.
Claims 1 (claims 2-5, 7, 8, 11, 12, 14, 16, 88 dependent therefrom) and 17 (claims 18, 82 83 and 89-92 dependent therefrom) are indefinite in the that they are drawn to a prime editor composition (claim 1) and a composition for prime editing (claim 17) comprising a Cas protein having double-stranded cleavage activity is indefinite in that the presence of double stranded cleavage activity in a composition appears to be contradictory to intended function of a prime editor composition. This is supported by applicants specification which states, (paragraph [0167]) “prime editing genomic DNA can avoid generating a double-stranded break”.
Further as is recognized in the art “Prime editing” is designed to not involve (say goodbye to) double stranded breaks and involve (say hello to) nicks (Scholefield and Harrison, Gene Therapy, Vol 28, pp 396-401, 2021). Thus a prime editor composition or a composition for prime editing having double stranded cleavage activity is contrary to what a prime editor composition is in the art and is thus indefinite.
Appropriate correction and/or comment is required.
Claim Rejections - 35 USC § 112
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(s) 1-5, 7, 8, 11, 12, 14, 16-18, 82 83 and 88-92 are rejected under this statute on the basis that applicants newly added recitation “a catalytically active Cas protein capable of causing a double stranded break in a DNA target” in the context of applicants claimed “prime editor composition” is not supported by applicants specification at the time of filing and is thus considered new matter.
This rejection was stated in the previous office action as it applied to previous claims 1-5, 7, 8, 11, 12, 14, 16-18, 82 83 and 88-92. In response to the rejection applicants have amended the claim and traverse the rejection as it applies to the newly amended claims.
Applicants traverse this rejection on the basis that applicants acknowledge the offices assertion that a catalytically active Cas protein having double-stranded cleavage activity in the in the context of a prime editor composition is new matter. Applicants submit that while primer editor compositions can avoid generating a double stranded break, the applicantion as filed also contemplates the use of Cas enzymes that can cause a double stranded break. In support of applicants position applicants point to a number of claims of applicants specification which are drawn to a “prime editor” or “system for prime editing” and comprise “an active Cas protein”. Applicants submit that the specificaiton clearly contemplates a prime editor compositon comprising an active Cas protein. Applicants further submit that the specification teaches that "[a] 'catalytically active RNA-guided DNA endonuclease protein,' or 'DNA endonuclease' refers to an endonuclease protein directed to a specific DNA target by a gRNA, where it causes a double-strand break." paragraph [0078] of the instant application. Applicants submit that therefore, the use of prime editor compositions with catalytically active Cas proteins having a double-stranded cleavage activity are contemplated and supported by the application as filed and the priority documents.
Applicants amendment of the claims and applicants complete argument is acknowledged and has been carefully considered, however is not found persuasive for the reasons previously made of record for those reasons repeated herein.
As stated previously, applicants comments regarding support for the above amendment at paragraph [0078] of the instant application is acknowledged, however, this submitted support is insufficient to support that applicants were in possession of the claimed prime editor comprising a polynucleotide encoding a catalytically active Cas protein having a double-stranded cleavage activity.
It continues that the basis of the lack of support is that while applicants have submitted that support is found in that portion of applicants specification that is drawn to generic terminology such as “Polynucleotides and polypeptides”, “Cas proteins”, “Reverse transcriptases” and such, support for the claimed “prime editor” is not found. The lack of support is further seen throughout applicants specification (paragraph [0027], [0048]) and priority documents 63/109,131 (paragraph [0167]) which states “prime editing genomic DNA can avoid generating a double-stranded break”.
In response to applicants submission that the specification teaches that "[a] 'catalytically active RNA-guided DNA endonuclease protein,' or 'DNA endonuclease' refers to an endonuclease protein directed to a specific DNA target by a gRNA, where it causes a double-strand break." paragraph [0078] and applicants submission that therefore, the use of prime editor compositions with catalytically active Cas proteins having a double-stranded cleavage activity are contemplated and supported by the application as filed and the priority documents is not found persuasive on basis that while it is recognized that applicants specification supports prime editor compositions with catalytically active Cas proteins, it does not support prime editor compositions with catalytically active Cas proteins having a double-stranded cleavage activity. Applicants do not define Cas proteins as having double stranded cleavage activity, but rather DNA endonucleases which are not synomoyous with Cas proteins.
Further as is recognized in the art “Prime editing” is designed to say goodbye to double stranded breaks and hello to nicks (Scholefield and Harrison, Gene Therapy, Vol 28, pp 396-401, 2021). Thus a prime editor composition or a composition for prime editing having double stranded cleavage activity is considered new matter.
Applicant is referred to the revised guidelines concerning compliance with the written description requirement of U.S.C. 112, first paragraph, published in the Official Gazette and also available at www.uspto.gov.
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.
The rejection of claim(s) 1-5, 7, 8, 11, 12, 14, 16, 17, 18, 82, 83, 88-90, 92 under 35 U.S.C. 102(a)(2) as being anticipated by Halperin (US 11,352,623) is withdrawn based upon applicants amendment of the claims in the paper of 6/20/2025.
Specifically Halperin does not teach the claimed prime editor wherein the Cas portion of the prime editor causes a double stranded break in a DNA (see also above rejection under 35 U.S.C. 112(b). Further Halperin teaches that “CRISPR nucleases may offer a straightforward approach to create targeted, double-stranded breaks in genomic DNA. However, precisely altering the sequence of a genomic target has been difficult due to inefficiency of homology-directed repair, toxicity of double-stranded breaks, and the challenge of delivering homologous donor DNA”.
It is noted that the withdrawal of the rejection is based upon applicants amendment of the claims in the paper of 6/20/2025 and not applicants arguments based upon the establishment of a priority date.
Claim Rejections - 35 USC § 103
The rejection of claim(s) 1-8, 11, 12, 14, 16, 17, 18, 82, 83, 88-90, 92 is/are rejected under 35 U.S.C. 103 as being unpatentable over Halperin (US 11,352,623) is withdrawn based upon applicants amendment of the claims in the paper of 6/20/2025.
Specifically Halperin does not teach the claimed prime editor wherein the Cas portion of the prime editor causes a double stranded break in a DNA (see also above rejection under 35 U.S.C. 112(b). Further Halperin teaches that “CRISPR nucleases may offer a straightforward approach to create targeted, double-stranded breaks in genomic DNA. However, precisely altering the sequence of a genomic target has been difficult due to inefficiency of homology-directed repair, toxicity of double-stranded breaks, and the challenge of delivering homologous donor DNA”.
It is noted that the withdrawal of the rejection is based upon applicants amendment of the claims in the paper of 6/20/2025 and not applicants arguments based upon the establishment of a priority date.
Remarks
No claim is allowed.
Conclusion
THIS ACTION IS MADE FINAL. 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 RICHARD G HUTSON whose telephone number is (571)272-0930. The examiner can normally be reached 6-3 EST Mon-Fri.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Robert Mondesi can be reached on (408) 918-7584. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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rgh
10/16/2025
/RICHARD G HUTSON/Primary Examiner, Art Unit 1652
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