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 .
Election/Restrictions
Applicant’s election of claims 330-342 and 344-351 drawn to a primer editor comprising an amino acid substitution relative to SEQ ID NO:81 in the reply filed on July 13, 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)).
Status of Claims
Claims 192 and 330-351 are currently pending in the instant application. Upon further consideration, claim 343 is hereby rejoined. Accordingly, claims 192 and 330-351 are under examination on the merits in the instant application.
Drawings
The drawings are objected to because not all Figures are clearly legible. See for instance Figures 4A, 5A-5B, and 69. In fact, no single Figure is clearly legible as none of the Figures are in black colored text/lines in their entirety. Note that the patent application content should be in black font for legibility. That is, all application papers must be clearly legible using black colored font text and black lines. See MPEP §608.01. In addition to the illegibility issues, some of the Figures contain undisguisable legends. See for instance Figure 71 showing that the four legends are not clearly distinguishable from each other thus the four bars in the graph are not clearly identifiable. Applicant is required to review all Figures and make appropriate corrections for clear legibility and clear distinction for different legends.
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.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed applications, Application Nos. 63/136,194 and 63/176,180, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. It is noted that the aforementioned ’194 and ‘180 provisional applications do not provide adequate written description support for the instantly claimed subject matter, in particular, the three recited amino acid substitutions in the nCas9. Accordingly, the effective filing date for claims 192 and 330-351 will be the filing date of Application No. 63/176,202, which is April 16, 2021.
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 349 is 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.
Claim 349 recites “One or more polynucleotides encoding the prime editor of claim 192.” It is unclear whether the plurality of polynucleotides are meant to be a mixture of identical polynucleotide sequences or whether the plurality of polynucleotides are meant to read on two different nucleotide sequences, one encoding “(i)” and the other encoding “(ii)”, of the prime editor of claim 192.
Claim Rejections - 35 USC § 103
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 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.
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.
Claims 192, 330-345, and 347-351 are rejected under 35 U.S.C. 103 as being unpatentable over Anzalone et al. (Nature, 2019, 576:149-157, applicant’s citation) in view of Spencer et al. (Scientific Reports, 2017, 7:16836, applicant’s citation), Liu et al. (US 2018/0127780 A1, applicant’s citation), and Ma et al. (Archives of Biochemistry and Biophysics, 2004, 422:153-160).
Anzalone discloses a “prime editor 2 (PE2)” composition comprising a “Cas9(H840A) nickase”, “an engineered M-MLV reverse transcriptase (D200N, L603W, T306K, W313F, T330P)”, and “a prime editing guide RNA (pegRNA)”, wherein the engineered M-MLV reverse transcriptase is fused to the C terminus of Cas9(H840A), wherein the PE2 composition provides efficient editing of a target nucleic acid in a cell. See page 152; Figure 2; Extended Data Figures 1d and 4a. It is noted that Anzalone’s “engineered M-MLV reverse transcriptase” has the amino acid sequence of SEQ ID NO:98 claimed in the instant case.
Anzalone teaches that the prime editor can further comprise “nicking sgRNAs”. See pages 153-155.
Anzalone does not teach that the “Cas9(H840A) nickase” further comprises R221K and N394K, wherein the nickase and the engineered M-MLV reverse transcriptase are linked via SEQ ID NO:105 and the prime editor further comprises SEQ ID NO:101 and SEQ ID NO:140.
Spencer teaches that the “combination of R221K and N394K showed the largest significant increase in activity”, which is about “1.5 times that of WT SpCas9”. See page 11.
Liu teaches that inclusion of an NLS “is critical for the nucleobase editor to be imported into the nucleus.” See paragraph 0038.
Liu teaches that multiple NLS can be added, wherein one or more NLS is added to the N-terminus, C-terminus, and/or an internal position to a genome editing fusion protein, wherein the NLS comprises “PKKKRKV (SEQ ID NO:373)” and the NLS can be “SV40 bipartite NLS (KRTADGSEFESPKKKRKV (SEQ ID NO:375)”. See paragraphs 0074-0075 and 0124.
It is noted that Liu’s SEQ ID NO:375 is 100% identical to SEQ ID NO:140 claimed in the instant case.
Liu teaches that the NLS can be added via a linker comprising “the amino acid sequence (SGGS)n (SEQ ID NO: 379)”, wherein n can be 2. See paragraph 0225.
Ma teaches that a protein having “a putative bipartite nuclear localization sequence (NLS)” in the N-terminal region has methionine as the first amino acid preceding the NLS, wherein methionine serves “as an initiator methionine” for protein translation, wherein the use of the first position methionine preceding the NLS “as a translational start site” is necessary for the protein to be localized to the nucleus. See pages 158-159; Table 1.
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify Anzalone’s PE2 comprising SpCas9 nickase with H840A by further incorporating R221K and N394K into the SpCas9 nickase. One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success so as to improve the activity of Anzalone’s prime editor because SpCas9 comprising R221K and N394K was known to provide a “significant increase in activity” as evidenced by Spencer.
It would also have been obvious to one of ordinary skill in the art before the effective filing date to incorporate art-recognized NLS sequences to the N-terminus, C-terminus, and the internal position of the above-modified PE2 comprising SpCas9 nickase comprising R221K, N934K, and H840A. One of ordinary skill in the art would have been motivated to do so in order to improve the prime editing activity of the above-modified prime editor because genome editing activity was known to occur in the nucleus thus the presence of multiple NLS in the N-terminus, C-terminus, and the internal position of a genome editing fusion protein was deemed “critical” for the fusion protein “to be imported into the nucleus” as taught by Liu, who taught that art-recognized NLS includes the amino acid sequence of “KRTADGSEFESPKKKRKV” that is identical to SEQ ID NO:140 claimed in the instant case. As such, one of ordinary skill in the art would have had a reasonable expectation of success in adding the art-recognized NLS sequence into each of the N-terminus, C-terminus, and the internal position of the above-modified PE2 fusion protein comprising SpCas9 nickase linked to the engineered M-MLV RT comprising five mutations. When adding the NLS sequence to the N-terminus of the fusion protein, one of ordinary skill in the art would have been motivated to add methionine as the first amino acid preceding the NLS sequence in order to efficiently translate the NLS as well as the entire fusion protein in view of the teachings of Ma, who taught that use of the first position methionine preceding the NLS “as a translational start site” is necessary for the protein to be localized to the nucleus, wherein the NLS having methionine added to “KRTADGSEFESPKKKRKV” is identical to SEQ ID NO:101 claimed in the instant case. When adding the NLS sequence to the internal position of the fusion protein, one of ordinary skill in the art would have been motivated to add (SGGS)2 linkers flanking the NLS sequence in order to link the SpCas9 nickase to the engineered M-MLV RT because use of such linkers for adding NLS to a genome editing fusion protein was an art-recognized methodology as evidenced by Liu, wherein the NLS flanked by (SGGS)2 on each side is identical to SEQ ID NO:105 claimed in the instant case. Taken together, one of ordinary skill in the art would have had a reasonable expectation of success in obtaining a prime editor comprising the amino acid sequence that is at least 80% identical to SEQ ID NO:99 claimed in the instant case.
In view of the foregoing, claims 192, 330-345, and 347-351 taken as a whole would have been prima facie obvious before the effective filing date sought in the instant case.
Claims 192, 330-336, 338, 340-345, and 347-351 are rejected under 35 U.S.C. 103 as being unpatentable over Liu et al. (Nature Communications, published online on April 9, 2021, 12:2121, applicant’s citation) in view of Spencer et al. (Scientific Reports, 2017, 7:16836, applicant’s citation).
Liu discloses an “NLS-optimized SpCas9-based prime editor” or “a nuclear localization signal sequence optimized PE2 (referred to as PE2*)” and a nucleic acid encoding the prime editor, wherein the prime editor comprises “C-myc NLS” and “BP-SV40 NLS” in the N-terminus and “vBP-SV40 NLS” and “SV40 NLS” in the C-terminus, wherein the SpCas9 nickase comprises H840A and is linked to M-MLV RT that “harbors five mutations” via a linker, wherein the prime editor also comprises a pegRNA and a nicking sgRNA, wherein the M-MLV RT is “from PE2” in Reference number 6, which is Anzalone et al. (Nature, 2019, 576:149-157). See pages 2-3 and 9; Figures 1a and 1c.
It is noted that Anzalone’s engineered M-MLV RT comprises “D200N, L603W, T306K, W313F, T330P”.
Liu does not teach that the SpCas9 nickase further comprises R221K and N394K.
Spencer teaches that the “combination of R221K and N394K showed the largest significant increase in activity”, which is about “1.5 times that of WT SpCas9”. See page 11.
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify Liu’s NLS-optimized prime editor comprising SpCas9 nickase with H840A by further incorporating R221K and N394K into the SpCas9 nickase. One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success so as to improve the activity of Liu’s prime editor because SpCas9 comprising R221K and N394K was known to provide a “significant increase in activity” as evidenced by Spencer.
Accordingly, claims 192, 330-336, 338, 340-345, and 347-351 taken as a whole would have been prima facie obvious before the effective filing date granted in the instant application.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 192, 330-345, and 347-351 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-30 of U.S. Patent No. 11,447,770 B1 in view of Anzalone et al. (Nature, 2019, 576:149-157, applicant’s citation), Spencer et al. (Scientific Reports, 2017, 7:16836, applicant’s citation), Liu et al. (US 2018/0127780 A1, applicant’s citation), and Ma et al. (Archives of Biochemistry and Biophysics, 2004, 422:153-160).
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are encompassed and/or rendered obvious by the ‘770 patent claims, which require a prime editing system comprising a fusion protein or a nucleic acid encoding the fusion protein, wherein the fusion protein comprises a “napDNAbp” and “a reverse transcriptase” and a PEgRNA and a gRNA core, wherein the “napDNAbp” is Cas9 comprising H840A and the reverse transcriptase is M-MLV RT. It would have been obvious to incorporate R221K and N394K into the napDNAbp of the ‘770 patent claims, engineer the M-MLV RT of the ‘770 patent claims to comprise “D200N, L603W, T306K, W313F, T330P” mutations, and add NLS sequences into the N-terminus, C-terminus, and internal position between the napDNAbp and M-MLV RT in view of the combined teachings of Anzalone, Spencer, Liu, and Ma for the reasons set forth in the §103 rejection above, which is fully incorporated by reference herein thus will not be repeated.
Claims 192, 330-345, and 347-351 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-30 of U.S. Patent No. 11,795,452 B2 in view of Spencer et al. (Scientific Reports, 2017, 7:16836, applicant’s citation), Liu et al. (US 2018/0127780 A1, applicant’s citation), and Ma et al. (Archives of Biochemistry and Biophysics, 2004, 422:153-160).
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are encompassed and/or rendered obvious by the ‘452 patent claims drawn to a prime editing system comprising “a prime editing guide RNA (PEgRNA)”, “a nicking single guide RNA (sgRNA)”, and a fusion protein or a nucleic acid encoding the fusion protein, wherein the fusion protein comprises a “napDNAbp” that is a Cas9 nickase comprising H840A and “a reverse transcriptase” comprising D200N, T306K, W313F, T330P, and L603W. It would have been obvious to incorporate R221K and N394K into the napDNAbp of the ‘452 patent claims and add NLS sequences into the N-terminus, C-terminus, and internal position between the napDNAbp and the reverse transcriptase in view of the combined teachings of Spencer, Liu, and Ma for the reasons set forth in the §103 rejection above, which is fully incorporated by reference herein thus will not be repeated.
Claims 192, 330-345, and 347-351 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-32 of U.S. Patent No. 12,509,680 B2 in view of Anzalone et al. (Nature, 2019, 576:149-157, applicant’s citation), Spencer et al. (Scientific Reports, 2017, 7:16836, applicant’s citation), Liu et al. (US 2018/0127780 A1, applicant’s citation), and Ma et al. (Archives of Biochemistry and Biophysics, 2004, 422:153-160).
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are encompassed and/or rendered obvious by the ‘680 patent claims drawn to a multiplex prime editing system comprising a PEgRNA and a fusion protein or a nucleic acid encoding the fusion protein, wherein the fusion protein comprises a “napDNAbp” that is a Cas9 nickase an M-MLV RT. It would have been obvious to incorporate R221K and N394K into the napDNAbp of the ‘680 patent claims, engineer the M-MLV RT of the ‘680 patent claims to comprise “D200N, L603W, T306K, W313F, T330P” mutations, and add NLS sequences into the N-terminus, C-terminus, and internal position between the napDNAbp and M-MLV RT in view of the combined teachings of Anzalone, Spencer, Liu, and Ma for the reasons set forth in the §103 rejection above, which is fully incorporated by reference herein thus will not be repeated.
Claims 192, 330-345, and 347-351 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-31 of U.S. Patent No. 12,570,972 B2 in view of Anzalone et al. (Nature, 2019, 576:149-157, applicant’s citation), Spencer et al. (Scientific Reports, 2017, 7:16836, applicant’s citation), Liu et al. (US 2018/0127780 A1, applicant’s citation), and Ma et al. (Archives of Biochemistry and Biophysics, 2004, 422:153-160).
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are encompassed and/or rendered obvious by the ‘972 patent claims drawn to a prime editing system comprising a PEgRNA and a fusion protein or a nucleic acid encoding the fusion protein, wherein the fusion protein comprises a “napDNAbp” that is a Cas9 nickase an M-MLV RT. It would have been obvious to incorporate R221K and N394K into the napDNAbp of the ‘972 patent claims, engineer the M-MLV RT of the ‘972 patent claims to comprise “D200N, L603W, T306K, W313F, T330P” mutations, and add NLS sequences into the N-terminus, C-terminus, and internal position between the napDNAbp and M-MLV RT in view of the combined teachings of Anzalone, Spencer, Liu, and Ma for the reasons set forth in the §103 rejection above, which is fully incorporated by reference herein thus will not be repeated.
Claims 192, 330-345, and 347-351 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-31 of U.S. Patent No. 12,624,354 B2 in view of Anzalone et al. (Nature, 2019, 576:149-157, applicant’s citation), Spencer et al. (Scientific Reports, 2017, 7:16836, applicant’s citation), Liu et al. (US 2018/0127780 A1, applicant’s citation), and Ma et al. (Archives of Biochemistry and Biophysics, 2004, 422:153-160).
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are encompassed and/or rendered obvious by the ‘354 patent claims drawn to a prime editing system comprising a PEgRNA and a fusion protein or a nucleic acid encoding the fusion protein, wherein the fusion protein comprises a “napDNAbp” that is a Cas9 nickase an M-MLV RT. It would have been obvious to incorporate R221K and N394K into the napDNAbp of the ‘354 patent claims, engineer the M-MLV RT of the ‘354 patent claims to comprise “D200N, L603W, T306K, W313F, T330P” mutations, and add NLS sequences into the N-terminus, C-terminus, and internal position between the napDNAbp and M-MLV RT in view of the combined teachings of Anzalone, Spencer, Liu, and Ma for the reasons set forth in the §103 rejection above, which is fully incorporated by reference herein thus will not be repeated.
Claims 192, 330-345, and 347-351 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 69 and 71-99 of copending Application No. 17/219,590 in view of Spencer et al. (Scientific Reports, 2017, 7:16836, applicant’s citation), Liu et al. (US 2018/0127780 A1, applicant’s citation), and Ma et al. (Archives of Biochemistry and Biophysics, 2004, 422:153-160).
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are encompassed and/or rendered obvious by the ‘682 claims, which are drawn to a prime editing system comprising a fusion protein or a nucleic acid encoding the fusion protein, wherein the fusion protein comprises a “napDNAbp” domain such as Cas9 comprising H840A and an M-MLV RT comprising D200N, T306K, W313F, T330P, and L603W, wherein the fusion protein is at least 85% identical to SEQ ID NO:134. It is noted that SEQ ID NO:134 of the ‘590 claims is at least 98% identical to SEQ ID NO:99 claimed in the instant case. It would have been obvious to incorporate R221K and N394K into the napDNAbp of the ‘590 claims and add NLS sequences into the N-terminus, C-terminus, and internal position between the napDNAbp and the reverse transcriptase in view of the combined teachings of Spencer, Liu, and Ma for the reasons set forth in the §103 rejection above, which is fully incorporated by reference herein thus will not be repeated.
Claims 192, 330-345, and 347-351 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 10-33 of copending Application No. 17/440,682 in view of Spencer et al. (Scientific Reports, 2017, 7:16836, applicant’s citation), Liu et al. (US 2018/0127780 A1, applicant’s citation), and Ma et al. (Archives of Biochemistry and Biophysics, 2004, 422:153-160).
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are encompassed and/or rendered obvious by the ‘682 claims, which are drawn to a prime editing system comprising a fusion protein or a nucleic acid encoding the fusion protein, wherein the fusion protein comprises a “napDNAbp” domain such as Cas9 comprising H840A and an “RT domain” such as M-MLV RT comprising D200N, T306K, W313F, T330P, and L603W. It would have been obvious to incorporate R221K and N394K into the napDNAbp of the ‘682 claims and add NLS sequences into the N-terminus, C-terminus, and internal position between the napDNAbp and the reverse transcriptase in view of the combined teachings of Spencer, Liu, and Ma for the reasons set forth in the §103 rejection above, which is fully incorporated by reference herein thus will not be repeated.
Claims 192, 330-345, and 347-351 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8, 10, 12-15, and 50-56 of copending Application No. 17/786,168 in view of Anzalone et al. (Nature, 2019, 576:149-157, applicant’s citation), Spencer et al. (Scientific Reports, 2017, 7:16836, applicant’s citation), Liu et al. (US 2018/0127780 A1, applicant’s citation), and Ma et al. (Archives of Biochemistry and Biophysics, 2004, 422:153-160).
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are encompassed and/or rendered obvious by the ‘168 claims, which are drawn to a prime editing system comprising a fusion protein or a nucleic acid encoding the fusion protein, wherein the fusion protein comprises a Cas9 nickase and an RT polypeptide such as M-MLV RT. It would have been obvious to incorporate R221K and N394K into the Cas9 nickase of the ‘168 claims, engineer the M-MLV RT of the ‘168 claims to comprise “D200N, L603W, T306K, W313F, T330P” mutations, and add NLS sequences into the N-terminus, C-terminus, and internal position between the napDNAbp and M-MLV RT in view of the combined teachings of Anzalone, Spencer, Liu, and Ma for the reasons set forth in the §103 rejection above, which is fully incorporated by reference herein thus will not be repeated.
Claim Objections
Claim 346 is 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.
Conclusion
Claims 192, 330-345, and 347-351 are rejected.
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/DANA H SHIN/Primary Examiner, Art Unit 1635
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