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
The action is written in response to applicant’s correspondence received on 6/19/2026. Claims 1-3, 9-10, 12-17, 23, 26-27, 33-34, 106, 108, 119-121, 123, and 144 are currently pending in the instant application.
Priority
The instant application claims priority to US Provisional Application 63/171,651, filed on 4/7/2021.
Election/Restriction
Applicant’s election of the inventions of Group I, claims 1-3, 9-10, 12-17, 23, 26-27, and 33, drawn to a polynucleotide drawn to a polynucleotide, has been acknowledged. Applicant makes the election with traverse and argues that Group II, drawn to a composition and a cell comprising said composition (claims 34 and 106) maintains unity with elected Group I as the compositions comprise the elected polynucleotide (i.e. ALL of Group I). Applicant’s arguments are found persuasive and the inventions of Group I and II will be rejoined and examined as a cell or composition comprising the polynucleotide of Group I.
Applicant’s election of the species:
Regarding the polynucleotide of claim 1: a DNA polymerase recruitment moiety, recited in claim 2.
With regards to the polynucleotide of claim 2: a basic site and phosphorothioate bond which is comprised in the modified nucleotide, recited in claim 3.
With regards to the polynucleotide of claim 2: a hairpin, recited in claim 9.
In the response filed on 6/19/2026 is acknowledged.
Claims 108, 119-121, 123, and 144 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to non-elected inventions.
Claims 9 and 12 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to non-elected species (drawn to a non-B DNA structure and DNA ligase recruitment moiety).
Applicant is reminded that upon the cancellation of claims to a non-elected invention, the inventorship must be corrected in compliance with 37 CFR 1.48(a) if one or more of the currently named inventors is no longer an inventor of at least one claim remaining in the application. A request to correct inventorship under 37 CFR 1.48(a) must be accompanied by an application data sheet in accordance with 37 CFR 1.76 that identifies each inventor by his or her legal name and by the processing fee required under 37 CFR 1.17(i).
Claims 1-3, 10, 13-17, 23, 26-27, 33-34, and 106 are under examination of the merits.
Specification
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency – Nucleotide and/or amino acid sequences appearing in the specification are not identified by sequence identifiers in accordance with 37 CFR 1.821(d).
Regarding species deficiencies, Fig. 14B shows representation of next-generation sequencing (NGS) results of the targeted insertion sequences. SEQ ID NOs for this sequence or sequences are not present in the figure drawings nor the brief descriptions of the figures in the specification.
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
The use of the term FUGENEHD® (paragraph 0202), LIPOFECTAMINE™ RNAiMAX (paragraph 0202), HIDI™ (paragraph 0209), which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears 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 Interpretation
Regarding claim 33 and 106, applicant recites a cell that comprises the polynucleotide of claim 1, or a composition of claim 34. Regarding these claims, though applicant describes the introduction of nucleic acids to a cell in vivo (see paragraph 0041) and where the viral vectors can be used in a wide variety of gene delivery application in cells, as well as living animal subjects (see paragraph 0043), applicant does not provide clear evidence that the cell of interest is in a human subject. Therefore, the cells that are claimed are interpreted to not read on a cell in a human subject.
Claim Rejections - 35 USC § 102
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 1-3, 10, 13-17, 23, 26-27, 33-34, and 106 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Liu et al. (WO 2020/191248 A1, published 9/24/2020), as disclosed in the IDS submitted on 4/26/2024.
Regarding claim 1, Liu teaches methods and compositions for editing nucleotide sequences, wherein Liu teaches compositions directed towards a new platform for genome editing called “prime editing”. Liu teaches prime editing is a versatile and precise genome editing method that directly writes new genetic information into a specified DNA site using a nucleic acid programmable DNA binding protein working in association with a polymerase (see paragraph 0008). Liu teaches wherein the prime editing system is programmed with a prime editing (PE) guide RNA (PEgRNA) that both specifies the target site and templates the synthesis of the desired edit in the form of a replacement DNA strand by way of an extension (either DNA or RNA) engineered onto a guide RNA (either at the 5’ or 3’ end, or an internal portion of the guide RNA) (see paragraph 0008).
Liu teaches where the guide RNAs or PEgRNAs may comprise various structural elements to include, but are not limited to a gRNA core, which refers to the sequence within the gRNA that is responsible for Cas9 binding (see paragraph 0206).
Liu further teaches where in Figs. 3A-3G, the PEgRNA comprises a 5’ extension arm comprising a primer binding site and a DNA synthesis template (see paragraph 0070). However, in a specific embodiment (Fig. 3A and 3B), Liu shows a 3’ editor gRNA and an intramolecular extension, which comprises the DNA template sequence, placing the DNA template sequence on the 3’ end of the polynucleotide (see paragraph 0082).
Therefore, Liu teaches a polynucleotide that can comprise of an RNA guide sequence, wherein the gRNA can comprise of a gRNA core (Cas-binding domain), and a DNA template sequence (DNA synthesis template) on the 3’ end.
Regarding claim 2, Liu teaches where the PEgRNA could comprise, in certain embodiments, secondary RNA structures, such as, but not limited to, hairpin, stem/loops, toe loops, RNA binding protein recruitment domains (e.g., the MS2 aptamer which recruits and binds to the MS2cp protein). Such secondary structures could be positioned within the spacer, the gRNA core, or the extension arm (see paragraph 0082). Here, Liu teaches an MS2 aptamer being positioned within the extension arm, which comprises the DNA template sequence. Looking to the specification for guidance, the instant application discloses the DNA template sequence could comprise a sequence of interest, a primer binding sequence and a sequence of interest (which is taught by the extension arm of Liu), or a template for amplification by a DNA polymerase (see paragraph 0098). Regarding Liu, an MS2 aptamer recruits and binds to the MS2 Coat Protein, which recruits DNA polymerase to the template sequence (such as reverse transcriptase as presented by Liu). Therefore, Liu teaches where the DNA template sequence comprises MS2 aptamer/MS2CP which is a DNA polymerase recruitment moiety as it recruits reverse transcriptase.
Liu also teaches if the extension arm is RNA, the DNA polymerase could be a reverse transcriptase or any suitable RNA-dependent DNA polymerase. If the extension arm is DNA, then the DNA polymerase could be a DNA-dependent DNA polymerase (see paragraph 0082).
Regarding claim 3, Liu teaches where the nucleic acid molecule may include…modified phosphate groups (e.g. phosphorothioates) (see paragraph 0227). Liu also teaches the PEgRNA may be improved by introducing modifications to the edit template region. Such modifications may include…locked-nucleic acids (LNA), 2’-O-methyl modifications, etc. (see paragraph 0661).
Regarding claim 10, Liu teaches where MS2 aptamer can be positioned on the extension arm, or the DNA template sequence region, which binds a MS2CP. MS2CP is a protein which recruits reverse transcriptase, a DNA polymerase (see paragraph 0082). Liu further teaches that it is of note that one of ordinary skill in the art will be able to select an appropriate DNA polymerase, depending on the nature of the nucleic acid materials of the extension arm (i.e. DNA or RNA), for use in prime editing that may be implemented either as a fusion with the NapDNAbp (PEgRNA) or provided in trans as a separate moiety. Liu teaches if the extension arm is DNA, the DNA polymerase could be a DNA-dependent DNA polymerase and teaches in various embodiments, provision of the DNA polymerase could be in trans, such as with an RNA-protein recruitment domain (see paragraph 0082).
Regarding claim 13, Liu teaches wherein the prime editing system is programmed with a prime editing (PE) guide RNA (PEgRNA) that both specifies the target site and templates the synthesis of the desired edit in the form of a replacement DNA strand by way of an extension (either DNA or RNA) engineered onto a guide RNA (either at the 5’ or 3’ end, or an internal portion of the guide RNA) (see paragraph 0008).
Liu further specifies a DNA synthesis template refers to the region or portion of the extension arm of a PEgRNA that is utilized as the template strand by a polymerase of a prime editor to encode a 3’ single-strand DNA flap that contains the desired edit (see paragraph 0189). Liu also teaches where the guide RNAs or PEgRNAs may comprise various structural elements to include, but are not limited to a gRNA core, which refers to the sequence within the gRNA that is responsible for Cas9 binding (see paragraph 0206). Liu teaches where the nucleic acid molecule may include…modified phosphate groups (e.g. phosphorothioates) (see paragraph 0227). Therefore, Liu teaches a polynucleotide that can comprise of an RNA guide sequence (i.e. PEgRNA), wherein the gRNA can comprise of a gRNA core (Cas-binding domain), and DNA template sequences (DNA synthesis template) on the 3’ end which can be modified with phosphorothioate groups or bonds.
Regarding claim 14, Liu teaches where the PEgRNA that both specifies the target site and templates the synthesis of the desired edit in the form of a replacement DNA strand (see paragraph 0008 and claim 11). One skilled in the art would recognize that a guide RNA that specifies the target site indicates a “sequence of interest” as recited in the instant claim. Furthermore, Liu teaches where the “primer binding site” refers to the nucleotide sequence located on a PEgRNA as a component of the extension arm (typically at the 3’ end of the extension arm) and serves to bind the primer sequence that is formed after Cas9 nicking of the target sequence by the prime editor (see paragraph 0246). Liu also recites in claim 6 wherein the PEgRNA of claim 1 has at least one nucleic acid extension arm further comprising a primer binding site (see claim 6).
Regarding claim 15, Liu teaches where PEgRNAs may comprise various structural elements to include, but are not limited to a gRNA core, which refers to the sequence within the gRNA that is responsible for Cas9 binding (see paragraph 0206). Here, the cas-binding region comprises RNA. Furthermore, Liu teaches where the PEgRNA may be referred to as a chimeric or hybrid PEgRNA which comprises an RNA portion (i.e. the guide RNA components including the spacer and gRNA core) and a DNA portion (i.e. the extension arm) (see paragraph 0239).
Regarding claim 16, Liu teaches where the intermolecular RNA extension is inserted into the gRNA, which refers to the portion of the guide RNA corresponding or comprising the tracrRNA (see paragraph 0616).
Regarding claim 17, Liu teaches a polynucleotide comprising a RNA guide, a Cas-binding region, and a DNA template sequence, wherein the DNA template sequence is at the 3’ end of the polynucleotide, as recited in claim 1. Liu further teaches in some embodiments, there an intermolecular RNA extension that is inserted into the gRNA. Liu defines the gRNA as the portion of the guide RNA corresponding or comprising the tracrRNA, which binds and/or interacts with the Cas9 protein or equivalent thereof (see paragraph 0616). Absent evidence to the contrary, one skilled in the art would recognize that the gRNA presented in Liu, which corresponds or comprises the tracrRNA, would be a Cas-binding region capable of “hybridizing” tracrRNA.
Regarding claim 23, Liu recites where the DNA synthesis template is at least 8 nucleotides, ranging up to 15 nucleotides (see claim 8).
Regarding claim 26, Liu teaches a PEgRNA of about 20 nucleotides which contains a nucleotide sequence that is complementary to the protospacer sequence in the target DNA sequence (see paragraph 0265).
Regarding claim 27, Liu teaches Fig. 3D which depicts a spacer sequence with a stem-loop structure between the guide RNA and the DNA template.
Regarding claim 33, Liu teaches a cell comprising said guide polynucleotide or composition (see paragraph 0047 and 1110).
Regarding claim 34, Liu teaches a composition comprising one or more of a napDNAbp (PEgRNA), a fusion protein, a reverse transcriptase, and an extended guide RNA (see paragraph 0048).
Regarding claim 106, Liu teaches a cell comprising said guide polynucleotide or composition (see paragraph 0047 and 1110).
In view of the foregoing, claims 1-3, 10, 13-17, 23, 26-27, 33-34, and 106 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Liu, as evidenced above.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DAVID YU whose telephone number is (571)272-1118. The examiner can normally be reached Monday-Friday 7:30 am -5 pm.
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, Ram Shukla can be reached at 571-272-0735. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/D.T.Y./Examiner, Art Unit 1635
/RAM R SHUKLA/Supervisory Patent Examiner, Art Unit 1635
Prosecution Insights