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 .
DETAILED ACTION
Applicant's preliminary amendment filed on May 2, 2023 is acknowledged. Claims 18-26 have been canceled. Claims 4-8 and 29 were amended. Claims 1-17 and 27-29 are pending.
Election/Restrictions
Applicant’s election of Group I (claims 1-17 and 27-28) in the reply filed on February 19, 2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claim 29 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claims 1-17 and 27-28 are examined on the merits herein.
Priority
PNG
media_image1.png
46
474
media_image1.png
Greyscale
Information Disclosure Statement
The information disclosure statement (IDS) submitted on September 22, 2023, March 6, 2025, and November 4, 2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Drawings
The drawings were received on May 2, 2023.
The drawings are objected to because:
- It is difficult to distinguish between the different lines in FIGS. 1G, 1H, 2E, 3C, 3F, 3G, and 6A-6C.
- It is difficult to distinguish between the different shadings in FIGS. 1E, 2D, 3B, 4A, 4C, and 11B.
- FIGS. 7A, 7B, 8A, 9A, 9E, and 12B through 12F are small and blurry making it difficult to decipher the figures.
- FIGS. 8B through 8D are blurry making it difficult to decipher the figures.
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.
Specification
The disclosure is objected to because of the following informalities:
Page 5, line 19 reads in part “the e first extended…”. It appears that there is a typographical error and “e” should not be present in between “the” and “first”.
Page 7, line 31 reads in part “Letter designations are imposed indicting how the flaps…”. It appears that there is a typographical error and “indicting” should read “indicating” instead.
The description of the drawings section of the specification refers to colors; however, the application does not have colored drawings.
Page 9, line 17 reads “Different error classes are colored the same as in (3C).”
Page 11, line 2 reads in part “red dotted line”.
Page 12, line 1 reads in part “highlighted in purple”.
Page 12, line 5 reads in part “Red vertical lines”.
Page 13, lines 10 and 14 reads in part “highlighted in yellow”.
Page 13, line 13 reads in part “highlighted in green”.
Page 21, line 10 reads in part “between about nucleotides long”. It appears that text is missing between “about” and “nucleotides”.
Appropriate correction is required.
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink 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. See e.g., pages 2, 41, and 45.
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 2-4 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 2-4, the phrase "and the like" renders the claim(s) indefinite because the claim(s) include(s) elements not actually disclosed (those encompassed by "and the like"), thereby rendering the scope of the claim(s) unascertainable. See MPEP § 2173.05(d).
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.
Claims 2, 3, 4, 14, and 15 are 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.
Claim 2 is drawn to the provision of a genus of functional nickase domains derived from CRISPR-associated (Cas) enzyme, Pyrococcus furiosus Argonaute, and the like, where the first editing complex and second editing complex creates a first and second single-stranded break in opposite strands of the dsDNA molecule and retain nickase ability. The claim encompasses less than the full Cas enzyme and Argonaute where the nickase domain may be derived from insertions, substitutions, and/or deletions. Claim 3 limits the Cas to Cas9, Cas12, Cas13, Cas3, CasΦ, and the like. The specification envisions that the functional nickase domain can be any functional domain that catalyzes a single stranded break in a target dsDNA sequence [page 22, last paragraph]. Thus, the claims encompass a genus of functional nickase domains defined as derived from or like Cas enzyme and Pyrococcus furiosus Argonaute having nicking activity on the first and second strands.
Claim 4 is drawn to the provision of a genus of functional reverse transcriptase domains derived from M-MLV RT, HIV RT, group II intron RT (TGIRT), superscript IV, and the like, where the functional reverse transcriptase domain of the first editing complex generates a first 3’ overhang and the second editing complex generates a second 3’ overhang. The specification envisions that the functional reverse transcriptase domain can be any functional domain that catalyzes reverse transcription reactions [page 23, last paragraph]. Thus, the claim encompasses a genus of functional reverse transcriptase domains as derived from or like M-MLV RT, HIV RT, group II intron RT (TGIRT), and superscript IV, having activity of generating a 3’ overhang.
Claims 14 and 15 are drawn to the provision of a genus of additional functional domains defined solely by function. The specification envisions that an additional functional domain can be a functional enzymatic domain such as a DNA repair protein domain. Inclusion of a DNA repair domain in the fusion editor protein can enhance the efficiency of DNA repair after generation of the 3’ overhang [page 24, first full paragraph]. Thus, the claims encompass a genus of additional functional domains defined solely by function of enhancing efficiency of 3’-overhang generation.
To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of a complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, and any combination thereof.
The specification envisions that examples of the functional nickase domain include Cas enzyme, Pyrococcus furiosus Argonaute, and the like, or a functional nickase domain derived therefrom. In some embodiments, the nickase domain is derived from an enzyme that has been modified, such as to ablate double stranded nuclease functionality. Non-limiting examples of Cas enzymes include Cas9, Cas12, Cas13, Cas3, CasΦ, and the like. Exemplary modifications include having one of multiple nuclease domains in the enzyme domain being inactivated [page 22, last paragraph bridging to page 23].
The specification envisions that examples of functional reverse transcriptase domains include avian myeloblastosis virus (AMV), RNase H, M-MLV (including wild-type and engineered domains), HIV RT, TGIRT, superscript IV, and the like, or a functional domain thereof [page 23, last paragraph bridging to page 24].
The specification discloses that a plasmid sequence encoding Cas9 and M-MLV-rt with 5 point mutations is available at Addgene depository. In addition, other Cas9 sequences, structures, and optimizations are those Cas9 nuclease sequences and structures known in the art. Further, Cas (e.g., Cas9) orthologs have been described in various species, including, but not limited to S. pyogenes and S. thermophilus [page 23, first paragraph]. The specification discloses that reverse transcriptase has been used primarily to transcribe mRNA into cDNA which can then be cloned into a vector for further manipulation and many such enzyme are known and encompassed by the disclosure (e.g., AMV, RNase H, M-MLV, and other exemplary non-limiting embodiments include HIV RT, TGIRT, and superscript IV) [page 23, last paragraph bridging to page 24]. The specification discloses that the first extended guide RNA and/or second extended guide RNA molecule can be engineered to include additional functional domains that aid in the efficiency of 3’-overhang generation. In one embodiment, the extended guide RNA incorporated structured RNA motifs at the 3’ terminus that enhance their stability and prevent degradation of the 3’ extension (e.g., evopreQ1 and pseudoknots) [page 22, first full paragraph]. The specification also discloses that an example of an additional functional domain is the functional DNA-binding domain from Rad15, or homologs thereof [page 24, first full paragraph].
Even if one accepts that the examples described in the specification meet the claim limitations of the rejected claims with regard to structure and function, the examples are only representative of a small group of functional nickase domains, functional reverse transcriptase domains, and additional functional domains. The results are not necessarily predictive of the broad genus of functional nickase domains, functional reverse transcriptase domains, and additional functional domains that are encompassed by the claims. Thus, it is impossible for one to extrapolate from the examples described herein those functional nickase domains, functional reverse transcriptase domains, and additional functional domains that would necessarily meet the structural/functional characteristics of the rejected claims.
The prior art does describe Cas9 protein and guide RNA complexes, where the Cas9 protein comprises two domains, the RuvC domain and HNH domain that nick opposite strands of DNA, such that inactivating mutations in the HNH domain creates a nickase that functions to nick the second strand of a double-stranded target DNA sequence as claimed (e.g., Cotta-Ramusino et al. WO 2017/180711, e.g., page 5, lines 17-21; Maizels et al. (Nucleic Acids Research, Vol. 46, No. 14, pages 6962-6973, July 9, 2018, e.g., page 6968, left column, 2nd full paragraph). The Cas9 nickase with an inactivating mutation in the HNH domain creates a nick 3 nucleotides upstream of the PAM (Gasiunas et al. (Proceedings of the National Academy of Sciences, USA, Vol. 109, No. 39, E2579-E2586, September 2012, including pages 1/8-8/8 of Supporting Information, e.g., Fig. 5). The prior art describes an Acidaminococcus sp. Cas12a (Cpf1) protein, which contains only a RuvC domain and no HNH domain, with a R1226A mutation that demonstrates nicking of the non-target DNA strand, and the guide RNA structure necessary for function (Yamano et al. Cell, Vol. 165, 949-962, May 5, 2016, including page S1-S7 of Supplemental Figures, and pages 1-2 of Supplemental Information, e.g., Fig. 6F). Cas12a (Cpf1) does not create a nick three nucleotides upstream of the protospacer adjacent motif in the nontarget (second) strand, rather it nicks after the 18th base (Zetsche et al. Cell, Vol. 163, pages 759-771, October 22, 2015; e.g., page 762, paragraph bridging columns; Fig. 3). The prior art describes Bacillus hisashii Cas12b (BhCas12b) and the associated guide RNA for nicking of a non-target DNA strand (Strecker et al. Nature Communications, Vol. 10, No. 1, 212, January 22, 2019, printed as pages 1-8, e.g., Abstract; page 2, paragraph bridging columns).
The prior art does describe a functional reverse transcriptase domain; however, Liu et al. (US 2023/0220374) teaches that the reverse transcriptase domain is a specific sequence and not a derivative thereof. Liu et al. teaches that the multi-flap prime editors may include a truncated version of M-MLV reverse transcriptase (SEQ ID NO: 766) [0553].
The prior art does not disclose inherent nickase activity on the non-target strand by any of the other specifically claimed proteins of Cas13, Cas3, CasΦ, and the like. The prior art does not teach specific mutation(s) that allow these other proteins to specifically nick the second strand of a double-stranded target as claimed, or to specifically nick three nucleotides upstream of a protospacer adjacent motif. Doudna et al. (US 2018/0346927) discloses Cas12e (CasX) and its guide RNA and generally envisions a CasX protein with nickase activity; however, Doudna et al. does not describe the specific mutation(s) that would create a CasX protein that nicks the non-target (second) strand of a double-stranded DNA. Doudna et al. (WO 2018/064352) discloses Cas12d (CasY) and its guide RNA and generally envision a CasY protein with nickase activity; however, Doudna et al. does not describe the specific mutation(s) that would create a CasY protein that nicks the non-target (second) strand of a double-stranded DNA. Yan et al. (Science, Vol. 363, No. 6422, pages 88-91, January 4, 2019, printed as pages 1/4-4/4, published online December 6, 2018.) teach Cas12c proteins that complex with guide RNA to cleave both stands of DNA near a minimal PAM sequence (e.g., page 3/4, paragraph bridging middle and right columns; Fig. 4C); however, Yan et al. does not describe specific mutation(s) that would create a Cas12c protein capable of nicking the non-target (second strand) of a double-stranded DNA. Yan et al. teach that the Cas12 members of type V CRISPR-Cas systems have weak sequence similarity and varied domain structure (e.g., page 1/4, paragraph bridging left and middle columns; Fig. 1). Neither the prior art nor specification describe the specific mutations capable of creating a nickase that is capable of nicking the second strand from a Cas12e, Cas12d, or Cas12c protein. Furthermore, although post-filing, Devillars et al. (International Journal of Molecular Sciences 2024) discloses that CRISPR/Cas13 systems from class VI are distinguishable from the other CRISPR systems in the sense that they naturally recognize and cleave ssRNA molecules according to a gRNA (Figure1d). Contrary to DNA targeting Cas proteins, Cas13 systems do not need to recognize a PAM sequence in order to cleave its target RNA [page 5, second full paragraph].
The prior art does not appear to offset the deficiencies of the instant specification
in that it does not describe a genus of functional nickase domains having nicking activity on the first and second strands, genus of functional reverse transcriptase domains having activity of generating a 3’ overhang, or a genus of additional functional domains having function of enhancing efficiency of 3’-overhang generation.
Therefore, the skilled artisan would have reasonably concluded applicants were
not in possession of the claimed invention for claims 2, 3, 4, 14, and 15.
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)(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 1-16 and 27-28 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Liu et al. (US 2023/0220374).
Regarding claims 1-3, Liu et al. teaches a multi-flap prime editing system that addresses the challenges associated with flap equilibration and subsequent incorporation of the edit into the non-edited complementary genomic DNA strand by simultaneously editing both DNA strands. In the dual-flap prime editing system, two pegRNAs are used to target opposite strands of a genomic site and direct the synthesis of two complementary 3′ flaps containing edited DNA sequence [0013], [1407], Figure 90, and Example 7. Liu et al. also teaches that multi-flap 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 (“napDNAbp”) working in association with a polymerase (i.e., in the form of a fusion protein or otherwise provided in trans with the napDNAbp), 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 (e.g., at the 5′ or 3′ end, or at an internal portion of a guide RNA) [0014]. Further, Liu et al. teaches a pair of prime editors, each comprising a nucleic acid programmable DNA binding protein (napDNAbp) and a reverse transcriptase. In various embodiments, each prime editor is capable of carrying out genome editing by target-primed reverse transcription in the presence of an extended guide RNA [0020]. In certain embodiments, the napDNAbp has a nickase activity and may be a Cas9 protein [0022].
Regarding claim 4, Liu et al. teaches that the multi-flap prime editors may include a truncated version of M-MLV reverse transcriptase (SEQ ID NO: 766) [0553]. Liu et al. also teaches that the multi-flap prime editor fusion protein may have the following amino acid sequence (referred to as “PE1”), which includes a Cas9 variant comprising an H840A mutation (i.e., a Cas9 nickase) and an M-MLV RT wild type, as well as an N-terminal NLS sequence (19 amino acids) and an amino acid linker (32 amino acids) that joins the C-terminus of the Cas9 nickase domain to the N-terminus of the RT domain [0640].
Regarding claims 5 and 6, Liu et al. teaches that each spacer sequence of each PEgRNA may bind to a specific binding site of the double-stranded DNA sequence adjacent the target site to be edited [0060].
Regarding claim 7, Liu et al. provides a schematic of dual-flap prime editing in Figure 90 (reproduced below). Specifically, a DNA target sequence is acted upon by two prime editing complexes (guided by pegRNA-A and pegRNA-B). The two pegRNAs target opposite strands of the double helix. Each prime editor (PE2pegRNA) nicks a single DNA strand, then synthesizes a 3′ DNA flap using the pegRNA as a template. The action of the two prime editor complexes results in the production of an intermediate containing two 3′ flaps on opposite strands of the DNA. The two 3′ flaps are complementarity to one another at their 3′ ends. Annealing of the 3′ ends of the 3′ flaps results in the formation of a double-duplex structure, with one duplex made of paired 3′ flaps containing the new DNA sequence (red), and the other duplex made of paired 5′ flaps containing the original DNA sequence (black). Excision of the intervening original DNA duplex (black paired 5′ flaps) yields a double-nicked DNA species containing the desired new DNA sequence (red) having replaced the original DNA sequence. Ligation of both nicks completes the editing process [0203].
PNG
media_image2.png
396
806
media_image2.png
Greyscale
Regarding claims 8-10, Liu et al. provides a schematic of dual-flap prime editing in Figure 90 (see above). Liu et al. also teaches in Example 7 the use of multi-flap prime editing, specifically using dual prime editors, for the precise insertion of new DNA sequence, the precise deletion of endogenous genomic DNA sequence, or the replacement of an endogenous genomic DNA sequence with a new DNA sequence [1841]. Specifically, two pegRNAs are used to target opposite strands of a genomic site and direct the synthesis of two complementary 3′ flaps containing edited DNA sequence. There is no requirement for the pair of edited DNA strands (3′ flaps) to directly compete with 5′ flaps in endogenous genomic DNA, as the complementary edited strand is available for hybridization instead. Since both strands of the duplex are synthesized as edited DNA, the dual-flap prime editing system obviates the need for the replacement of the non-edited complementary DNA strand required by classical prime editing. Instead, cellular DNA repair machinery need only excise the paired 5′ flaps (original genomic DNA) and ligate the paired 3′ flaps (edited DNA) into the locus. Therefore, there is also no need to include sequences homologous to genomic DNA in the newly synthesized DNA strands, allowing selective hybridization of the new strands and facilitating edits that contain minimal genomic homology. Nuclease-active versions of prime editors that cut both strands of DNA could also be used to accelerate the removal of the original DNA sequence [1845]. Further, depending on the orientation of the staggered DNA nicks generated by dual prime editors, the system can either replace the sequence between the two nicks with a new desired sequence (5′ overhang staggered orientation), or insert new DNA sequence with concomitant target site duplication (3′ overhang staggered orientation) [1846].
Regarding claim 11, Liu et al. teaches that an extension arm is a single strand extension at the 3′ end or the 5′ end of the PEgRNA which comprises a primer binding site and a DNA synthesis template sequence that encodes via a polymerase (e.g., a reverse transcriptase) a single stranded DNA flap containing the genetic change of interest, which then integrates into the endogenous DNA by replacing the corresponding endogenous strand, thereby installing the desired genetic change [0260]. Liu et al. also teaches that genetic changes that are possible with the prime editing processes described includes inversions [0102].
Regarding claims 12 and 13, Liu et al. teaches that the second nick can be positioned at least 5 nucleotides downstream of the first nick or in certain embodiments the second nick can be introduced between about 5-150 nucleotides on the unedited strand away from the site of the PEgRNA-induced nick [0319].
Regarding claims 14 and 15, Liu et al. teaches that to further improve the dual flap editing efficiency, a pseudoknot evoPreQ1 motif was introduced to protect the pegRNA 3′ end. Liu et al. teaches that in comparing the editing efficiency generated by the unmodified and evoPreQ1-modified dual pegRNAs, there was an overall increase of the editing efficiency with modified pegRNAs at the targeted IDS locus. The improvement of dual-flap editing efficiency can reach up to 5.3-fold [1866].
Regarding claim 16, Liu et al. teaches that the spacer sequence is the sequence in the guide RNA or PEgRNA (having about 20 nts in length) which binds to the protospacer in the target DNA [0258].
Regarding claims 27 and 28, Liu et al. teaches systems and methods for simultaneously editing both strands of a double-stranded DNA sequence at a target site to be edited. The systems comprise a first and second prime editor complex, wherein each of the first and second prime editor complexes comprises (1) a prime editor comprising (i) a nucleic acid programmable DNA binding protein (napDNAbp), and (ii) a polypeptide having an RNA-dependent DNA polymerase activity; and (2) a pegRNA comprising a spacer sequence, gRNA core, a DNA synthesis template, and a primer binding site, wherein the DNA synthesis template encodes a desired DNA sequence or a complement thereof, wherein the desired DNA sequence and the complement thereof form a duplex comprising an edited portion which integrates into the target site to be edited [abstract]. Liu et al. also teaches cells comprising a prime editor and an extended guide RNA [0064]. Further, Liu et al. teaches a plurality of PEgRNAs for use in multi-flap prime editing. In some embodiments, the plurality comprises a first, a second, a third, and a fourth PEgRNA [0075].
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim 17 is rejected under 35 U.S.C. 103 as being unpatentable over Liu et al. (US 2023/0220374) as applied to claims 1-16 and 27-28 above, and further in view of Chen et al. (US 2016/0298134).
Regarding claim 17, the teachings of Liu et al. are discussed above.
However, Liu et al. does not teach that the first guide domain and second guide domain are independently between about 25 and 40 nucleotides long.
Chen et al. teaches that the first region of the guide RNA is complementary to sequence (i.e., protospacer sequence) at the target site in the chromosomal sequence such that the first region of the guide RNA can base pair with the target site. In various embodiments, the first region of the guide RNA can comprise from about 10 nucleotides to more than about 25 nucleotides [0083].
It would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the multi-flap prime editing system of Liu et al. wherein the first guide domain and second guide domain are independently about 25 nucleotides long because Liu et al. taught a multi-flap prime editing system and Chen et al. taught that the first region of the guide RNA is complementary to sequence (i.e., protospacer sequence) at the target site in the chromosomal sequence such that the first region of the guide RNA can base pair with the target site and wherein the first region of the guide RNA can comprise about 25 nucleotides. One of ordinary skill in the art would have made such a modification because it would have amounted to a simple substitution of one known element for another to obtain predictable results.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHRISTINA TRAN whose telephone number is (571)270-0550. The examiner can normally be reached M-F 7:30 - 5:00pm.
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, 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.
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.
/C.T./
Examiner, Art Unit 1637
/Jennifer Dunston/Supervisory Patent Examiner, Art Unit 1637
Prosecution Insights