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 .
Status of Application/Amendment/Claims
This Office action is in response to the communications filed on June 24, 2026.
Currently, claims 1-10 are pending in the instant application. Claims 5-9 are withdrawn from further consideration as being drawn to a nonelected invention. Accordingly, claims 1-4 and 10 are under examination on the merits in the instant application.
The following rejections are either newly applied or are reiterated and are the only rejections and/or objections presently applied to the instant application.
Response to Arguments and Amendments
Withdrawn Rejections
Any rejections/objections not repeated in this Office action are hereby withdrawn.
Response to Declaration
The declaration under 37 CFR 1.130(a) filed on June 24, 2026 is sufficient to overcome the rejection of claims 1-4 based on Jeong et al. (Research Square, 2020).
Maintained Rejections
Claim Rejections - 35 USC § 112
Claims 1-4 remain rejected under 35 U.S.C. 112(b) as being indefinite for the reasons as set forth in the Office action mailed on March 24, 2026 and for the reasons stated below.
Applicant's arguments filed on June 24, 2026 have been fully considered but they are not persuasive. Applicant argues that one of ordinary skill in the art would understand the claims as amended are definite by pointing out the concurrently filed §1.132 declaration. In response, the declaration filed under 37 C.F.R. §1.132 is not found persuasive. As an initial matter, the declarant is not the absolute authority in the field such that all of the statements made by the declarant without any objective, scientific evidence are credible thus should be given weight. There is no supporting document provided with the declaration. The declaration is merely full of personal opinion statements. The only non-personal aspect of the declaration pertaining to the §112(b) rejection is the reference to “Figure 3A”. It is noted that Figure 3A shows “wtTadA”, which is presumed to from E. coli, is now identified as SEQ ID NO:3 and has “P” at amino acid residue 48. However, the instant claims do not recite SEQ ID NO:3 having “P” at 48. As such, “the wild type tRNA-specific Escherichia coli adenosine deaminase” is not clearly defined. In fact, the wild-type E. coli tRNA adenosine deaminase A (tadA) was known to have the “N” amino acid residue at position 48 as clearly evidenced by Figure 1 of Wolf et al. (The EMBO Journal, 2002, 21:3841-3851). Even better, the TadA7.10 of E. coli as appears to be claimed in claim 2 was known to have the “A” amino acid residue at position 48 as clearly evidenced by Figure 2b of Gaudelli et al. (Nature, 2017, 551:464-471, of record). As such, the declarant’s simplistic personal opinion that any person of ordinary skill in the relevant art would immediately understand that a wild-type tadA is known to have the “P” amino acid at position 48 is not objectively supported by any scientific evidence thus is found ineffective and unpersuasive to show that the mere words that are newly introduced “wherein” clause help render the claims definite under §112(b). As clearly and objectively evident in Wolf and Guadelli, art-recognized wild-type TadA species were not known to have the “P” residue at position 48 thus the examiner is at a loss as to the claimed subject matter and the assertions made in the declaration, which is not found credible, let alone persuasive in view of Wolf and Gaudelli, who do not teach position 48 being “P” in a wild-type E. coli TadA. It is interesting to note that applicant and the declarant completely dismissed and failed to address Gaudelli mentioned in the last Office action.
Also note that “if the language of a claim, given its broadest reasonable interpretation, is such that a person of ordinary skill in the relevant art would read it with more than one reasonable interpretation, then a rejection under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph is appropriate.” (emphasis added). See MPEP §2173.02.
In the instant case, the “wild type” sequence is amenable to a sequence having “N” or “A” at amino acid residue 48, none of which is the required “P”. That is, the “wild type” is amenable to more than one reasonable claim interpretation, thereby rendering the claims indefinite. Again, there is no specific, precise sequence identified/claimed for the wild type that indeed has the required “P” at the required position.
Accordingly, this rejection is maintained.
Claim Rejections - 35 USC § 112
Claims 1-4 remain rejected under 35 U.S.C. 112(a) as failing to comply with the written description requirement for the reasons as set forth in the Office action mailed on March 24, 2026 and for the reasons stated below.
Applicant's arguments filed on June 24, 2026 have been fully considered but they are not persuasive. Applicant argues that the data presented in the instant specification’s Examples 3-4 and Figures 5-9 together with the prior art knowledge are sufficient to describe the genus because one of ordinary skill in the art would understand that the “particular TadA7.10 construct” that is disclosed in the specification “may be applicable across multiple ABE backbones” and “can be extended to other Cas9 proteins.” In response, it is noted that applicant’s arguments merely amount to assertions without any objective supporting evidence. Applicant did not provide any scientific, factual reasoning as to why the single species disclosed in the specification represents all structural variants encompassed by the instantly claimed genus. Note that “it is incumbent upon applicant to come forth with countervailing evidence to rebut the rejection made by the examiner.” Ex parte Webb, 30 USPQ2d 1064, 1067-68 (Bd. Pat. App. & Int.1993). Hence, applicant’s conclusory statement without any objective evidence corroborating the statement confers little or no weight.
The concurrently filed §1.132 declaration is no better. The declarant merely states, without any objective, factual evidence, that it is his personal opinion that similar results “are expected to be reproducible”. The declarant’s conclusory statement without any corroborating, underlying factual evidence bears no weight in showing that the instant specification itself demonstrates the possession of the entire genus or a representative number of species.
Note that “expert opinion that an application meets the requirements of 35 U.S.C. 112 is not entitled to any weight; however, facts supporting a basis for deciding that the specification complies with 35 U.S.C. 112 are entitled to some weight” and “declarant’s opinion on the ultimate legal issue is not evidence in the case”, wherein a declaration which states “only conclusions” “may have little weight when considered in light of all the evidence of record in the application.” (emphasis added). See MPEP §716.01(c).
Since applicant’s arguments and the declarant’s statements are found ineffective and unpersuasive for the reasons stated above, this rejection is maintained.
Claim Rejections - 35 USC § 103
Claims 1 and 4 remain rejected under 35 U.S.C. 103 as being unpatentable over Liu et al. for the reasons as set forth in the Office action mailed on March 24, 2026 and for the reasons stated below.
Applicant's arguments filed on June 24, 2026 have been fully considered but they are not persuasive. Applicant argues that the claims are not obvious because the P48R mutation’s effect “would not have been predictable” because Liu does not disclose TadA with P48R. In so arguing, applicant points out the concurrently filed §1.132 declaration. The declarant provides a conclusory statement, without any factual evidence, that the effect of the P48R mutation would not have been predicted and that such mutation “is an unexpected and surprising functional change that is not clearly explained structurally.” It is unclear whether the declarant intended to assert “unexpected and surprising” effects pertaining to the instantly claimed P48R mutation. If so, applicant’s attention is directed to the fact that the rejected claims are not commensurate in scope with the disclosed, single structure species. Note that the “objective evidence of nonobviousness must be commensurate in scope with the claims which the evidence is offered to support.” See MPEP §716.02.
The examiner is bewildered by the declarant’s and applicant’s discussion of Gaudelli, which is not cited in the instant rejection thus bears no relevance to the obviousness rationale pertaining to the instant rejection.
The declarant in the §1.132 declaration states “the mere presence of arginine at the corresponding position in an ortholog would not have allowed a skilled artisan to predict increased cytosine editing activity.” The declarant further states that the “R” substitution was not known for “particularly high cytosine editing activity”. In response, the examiner is unable to understand why “increased cytosine editing activity” or “particularly high cytosine editing activity” should be predicted or required in rendering the instant claims obvious under §103. Note that such activity is not a claimed feature, and furthermore, the instant obviousness rejection is not established on a rationale of providing “increased” or “particularly high” cytosine editing activity. As such, the declarant’s statements are completely irrelevant thus are found unpersuasive to rebut the rejection of record.
In view of the foregoing, this rejection is maintained.
Claim 3 remains rejected under 35 U.S.C. 103 as being unpatentable over Liu et al. in view of Rees et al. for the reasons as set forth in the Office action mailed on March 24, 2026 and for the reasons stated below.
Applicant's arguments filed on June 24, 2026 have been fully considered but they are not persuasive. Applicant argues that Rae does not cure the deficiencies of Liu. In response, neither applicant nor the declarant clearly established the alleged “deficiencies of Liu” for the reasons stated hereinabove. Neither applicant nor the declarant adequately addressed the obviousness rationale over Liu as set forth in the last Office action as explained above.
Accordingly, this rejection is maintained.
New Rejections Necessitated by Amendment
Claim Rejections - 35 USC § 112
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim 10 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 10 directly depends from claim 1, which is found indefinite for the reasons of record as set forth in the last Office action and for the reasons explained hereinabove. Accordingly, claim 10 that reads on a wild type TadA having no “P” residue at position 48 is deemed indefinite for the same reasons for finding claim 1 indefinite.
Claim Rejections - 35 USC § 112
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim 10 is 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 10 directly depends from claim 1, which is found insufficient to describe the entire genus for the reasons of record as set forth in the last Office action and for the reasons explained hereinabove. The Cas9 species recited in claim 10 is far from adequately supporting a representative number of species of the instantly claimed base editor as the D10A mutation-containing Cas9 is far from addressing the genus of “adenosine deaminase variant”.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over Liu et al. (US 2018/0073012 A1, of record).
Claim 10 directly depends from claim 1, which is found prima facie obvious over Liu for the reasons of record as set forth in the last Office action and for the reasons explained hereinabove thus the obviousness rationale for claim 1 will not be repeated. It is further noted that Liu taught an ABE comprising a Cas9 domain, which “comprises a D10A mutation”. See paragraphs 0217-0222.
Accordingly, the structure of claim 10 would have been prima facie obvious for the reasons for finding claim 1 obvious as set forth in the last Office action, further in view of Liu’s teachings pertaining to a D10A mutation-containing Cas9.
Conclusion
No claim is allowed.
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 DANA H SHIN whose telephone number is (571)272-8008. The examiner can normally be reached Monday-Thursday: 8am - 6:30pm.
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.
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/DANA H SHIN/Primary Examiner, Art Unit 1635
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