DETAILED ACTION
All objections and rejections stated in prior Office Actions are withdrawn unless restated below.
Claims 2, 4, 11 and 14 remain withdrawn.
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 .
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 72 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.
Regarding claim 72, claim 72 recites an “editing frequency in RNA of 0.3% or less when contacted with a DNA comprising a target sequence.” It is unclear how editing of RNA occurs at any frequence wherein the base editor is contacted with DNA rather than RNA. For example, it is unclear if embodiments of claim 72 would include a latent property of the DNA base editor when 1) contacted with DNA comprising a target with no RNA present or only RNA present is a gRNA for the base editor, or 2) contacted with DNA comprising a target with RNA that does not include any sequence corresponding to the target sequence. It is noted that all base editors would appear to have an RNA editing frequence of zero when not contacted with RNA. For these reasons, an ordinarily skilled artisan cannot determine how to avoid infringement.
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 1, 3, 5, 9, 10, 12, 13, 16, 56, 64, 65, 69, 72, 76 and 189-193 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 14 of copending Application No. 17/797,700 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other for the following reasons.
The copending claims recite:
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The base editor ABE8e recited in copending claim 14 is understood to be the same ABE8e base editor recited in claim 76, which is stated to be SEQ ID NO: 202 of the copending specification. SEQ ID NO: 202 of the copending application is identical to recited SEQ ID NO: 169. Further, SEQ ID NO: 202 of the copending application has substitutions T111R, D119N, F149Y, A109S, H122N, Y147D, T166I, and Y147D. As such, the copending claims anticipate at least claims 1, 3, 5, 9, 10, 12, 13 and 56.
Regarding claims 64, 65, 69, 72, and 76, these claims recite a composition of matter and do not require the active performance of any method or editing of any DNA/RNA. Rather, these claims only require a base editor to latently have the recited properties under some unrecited condition (e.g. target site, gRNA, assay system, etc.). The specification evidences that the base editor ABE8e (recited SEQ ID NO: 167) is an embodiment of all of claims 64, 65, 69, 72, and 76.
Regarding claim 16, an alignment between SEQ ID NO: 202 of Application No. 17/797,700 and recited SEQ ID NO: 324 is below wherein amino acid residues 184 of 185 of SEQ ID NO: 202 are I and N, respectively, corresponding to position T166 and D167 as recited. As such, the based edition of SEQ ID NO: 202 of the reference specification and recited in the claims thereof further meets the features of claim 16. This rejection is necessitated by applicant’s amendment wherein it was not previously apparent that number of claim 16 is in accordance with SEQ ID NO: 324.
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Regarding claim 189, SEQ ID NO: 202 of Application No. 17/797,700 (identical to recited SEQ ID NO: 169) is understood to be a fusion polypeptide containing an adenosine deaminase including the specific substitutions recited in claims 190-192, as discussed above and a Cas9 domain as a napDNAbp domain as recited in claims 189 and 193.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 3, 5, 9, 10, 12, 13, 16, 56, 64, 65, 69, 72, 76 and 189-193 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 10 of copending Application No. 17/921,971 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other for the following reasons.
Copending claim 10 recites a method employing a base editor identified as ABE8e, which is SEQ ID NO: 379 of the copending applicant and identical to recited SEQ ID NO: 169.
This based editor has substitutions T111R, D119N, F149Y, A109S, H122N, Y147D, T166I, and Y147D. As such, the copending claims anticipate at least claims 1, 3, 5, 9, 10, 12, 13 and 56.
Regarding claims 64, 65, 69, 72, and 76, these claims recite a composition of matter and do not require the active performance of any method or editing of any DNA/RNA. Rather, these claims only require a base editor to latently have the recited properties under some unrecited condition (e.g. target site, gRNA, assay system, etc.). The specification evidences that the base editor ABE8e (recited SEQ ID NO: 167) is an embodiment of all of claims 64, 65, 69, 72, and 76.
Regarding claim 16, an alignment between SEQ ID NO: 379 of Application No. 17/921,971 and recited SEQ ID NO: 324 is below wherein amino acid residues 184 of 185 of SEQ ID NO: 379 are I and N, respectively, corresponding to position T166 and D167 as recited. As such, the based edition of SEQ ID NO: 379 of the reference specification and recited in the claims thereof further meets the features of claim 16. This rejection is necessitated by applicant’s amendment wherein it was not previously apparent that number of claim 16 is in accordance with SEQ ID NO: 324.
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Regarding claim 189, SEQ ID NO: 379 of Application No. 17/921,971 (identical to recited SEQ ID NO: 169) is understood to be a fusion polypeptide containing an adenosine deaminase including the specific substitutions recited n claims 190-192, as discussed above and a Cas9 domain as a napDNAbp domain as recited in claims 189 and 193.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 3, 5, 9, 10, 12, 13, 15, 16, 56, 64, 65, 69, 72, 76 and 189-193 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 19 and 27 of copending Application No. 18/927,415 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other for the following reasons.
Copending claim 19 and 27 recites a method employing a base editor identified as ABE8e(V106W), which is SEQ ID NO: 433 of the copending application having an additional substitution V106W and identical to recited SEQ ID NO: 188.
This based editor has substitutions V106W, T111R, D119N, F149Y, A109S, H122N, Y147D, T166I, and Y147D. As such, the copending claims anticipate at least claims 1, 3, 5, 9, 10, 12, 13, 15 and 56. Further, the base editor ABE8e (also recited in copending claim 27) has substitutions T111R, D119N, F149Y, A109S, H122N, Y147D, T166I, and D167N and is identical to recited SEQ ID NO: 166.
Regarding claims 64, 65, 69, 72, and 76, these claims recite a composition of matter and do not require the active performance of any method or editing of any DNA/RNA. Rather, these claims only require a base editor to latently have the recited properties under some unrecited condition (e.g. target site, gRNA, assay system, etc.). The specification evidences that the base editor ABE8e (recited SEQ ID NO: 167) is an embodiment of all of claims 64, 65, 69, 72, and 76.
Regarding claim 16, SEQ ID NO: 433 of the copending application has all of the substitutions recited in claim 16, wherein the rejection to claim 16 is necessitated by applicant’s amendment wherein it was not clear that numbering is in regards to SEQ ID NO: 324.
Regarding claim 189, SEQ ID NO: 379 of Application No. 18/927,415 (identical to recited SEQ ID NO: 188) is understood to be a fusion polypeptide containing an adenosine deaminase including the specific substitutions recited in claims 190-192, as discussed above and a Cas9 domain as a napDNAbp domain as recited in claims 189 and 193.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to arguments
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The claims recite a composition of matter and do not require the performance of any active step of a method. An embodiment of claim 72 is a base editor being a single polypeptide present in a buffer with the presence of no further proteins, DNA or RNA, including the same being present in a -80[Symbol font/0xB0]C. Claim 72 only recites latent properties that the base editor has if it were employed for editing nucleic acids, which is not required for infringement of claim 72. The claims expressly recite contact with DNA only. The claims do not recite “when contacted with DNA and RNA both comprising a target sequence.” Rather, claim 72 provides the conundrum of “when [a base editor is] contacted with DNA comprising a target system” in an in vitro system having only DNA and no RNA how to assess “editing frequence in RNA” when no RNA is required to be present. This presents substantial difficulty in determining if any base editor is capable of meeting the limitations of claim 72; for example, if editing frequency in RNA indirectly requires RNA to be present and/or if such RNA is required to have a correspondence target sequence.
Regarding claims 64, 65 and 69, the recited target sequence and adenosine to be edited is generic in the claims. A typical embodiment may be as presented in Fig. 7A:
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Three adenosine bases in vicinity of the indicated target sequence (sown boxed) are edited at different rates by the same base editor, with A1 having a particularly poor editing rate. If A1 or A7 were used assess if the limitations of claim 65, a 70% editing efficiency is not reached for a base editor SaABE8e. If A5 is used to asses editing rate, then maybe the 70% editing efficiency of claim 65 is reached, which raises a question of whether SaABE8e is reached or not. However, in reconsideration of the rejection, if there is some potential setup of DNA substrate to be edited and conditions wherein the indel formation rate of claim 64, editing efficiency of claim 65 or off-target DNA editing frequency of claim 69 can be reached, the same will be considered to meet the features of such claims.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 TODD M EPSTEIN whose telephone number is (571)272-5141. The examiner can normally be reached Mon-Fri 9:00a-5:30p.
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/TODD M EPSTEIN/Primary Examiner, Art Unit 1652