DETAILED CORRESPONDENCE
Status of the Application
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on December 22, 2025 has been entered.
Claims 1, 4, 8, 11-14, 17, and 396-400 are pending in the application.
Applicant’s amendment to the claims, filed December 22, 2025 is acknowledged. This listing of the claims replaces all prior versions and listings of the claims.
Applicant’s remarks filed December 22, 2025 in response to the final rejection filed September 26, 2025 and the advisory action filed December 3, 2025 have been fully considered.
The text of those sections of Title 35 U.S. Code not included in the instant action can be found in a prior Office action.
Restriction/Election
In response to a requirement for restriction/election mailed June 6, 2024, applicant elected without traverse the invention of Group I, corresponding to pending claims 1, 4, 8, 11-14, 17, and 396-400, and the species of S661T in the reply filed August 5, 2024.
All pending claims are drawn to the elected invention and are being examined on the merits.
Priority
This application is filed under 35 U.S.C. 371 as a national stage of international application PCT/US2019/044480, filed on July 31, 2019, which claims domestic priority under 35 U.S.C. 119(e) to U.S. provisional application numbers 62/712,809, 62/751,421, 62/775,865, 62/822,639, and 62/873,031, filed on July 31, 2018, October 26, 2018, December 5, 2018, March 22, 2019, and July 11, 2019, respectively.
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), 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 disclosures of the prior-filed applications, U.S. provisional application numbers 62/712,809, 62/751,421, and 62/775,865 fail to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) for claims 1, 4, 8, 11-14, 17, and 396-400 of this application. For example, the provisional application numbers 62/712,809, 62/751,421, and 62/775,865 fail to provide descriptive support for the recited mutations in claim 1. Claims 1, 4, 8, 11-14, 17, and 396-400 have an effective filing date of March 22, 2019.
Claim Objections
Claim 1 is objected to in the recitation of “97% sequence identity to a human adenosine deaminase that act on RNA 2” and in the interest of improving claim form and grammar, it is suggested that the noted phrase be amended to recite “97% sequence identity to the amino acid sequence of a human adenosine deaminase that acts
Claims 396, 398, and 400 are objected to because there is no conjunction connecting between “exosomes” and “microvesicles” and in the interest of improving claim form and grammar, it is suggested that the conjunction “or” be inserted between “exosomes,” and “microvesicles.”
Claim Rejections - 35 USC § 112(b)
The rejection of claims 1, 4, 8, 11-14, and 17 under 35 U.S.C. 112(b) as being indefinite in the recitation of “a homologous hADAR2 protein of the same species, or an ortholog of hADAR2 protein of a different species and consisting of no more than 40 mutations…wherein the amino acid numbering corresponds to the…corresponding position in the homologous hADAR2 or orthologous hADAR2” in claim 1 is withdrawn in view of applicant’s amendment to claim 1 to delete the phrase at issue,
the rejection of claims 11-14 and 17 under 35 U.S.C. 112(b) as being indefinite in the recitation of “engineered adenosine deaminase or a catalytic domain thereof of claim 1” (claims 11, 13, and 14) or “adenosine deaminase protein or catalytic domain thereof” (claim 17) is withdrawn in view of applicant’s amendments to claims 11, 13, 14, and 17 to delete the phrases at issue, and
the rejection of claim 8 under 35 U.S.C. 112(b) as being indefinite in the recitation of “the functional domain comprises a dead CRISPR-Cas protein or CRISPR-Cas nickase protein and a guide molecule comprising a sequence that hybridizes to a target sequence” is withdrawn in view of applicant’s amendment to claims 4 and 8.
Claims 1, 4, 8, 11-14, 17, and 396-400 are newly rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Claim 1 (claims 4, 8, 11-14, 17, and 396-400 dependent therefrom) recites the limitation “the amino acid sequence having at least 97% sequence identity to a human adenosine deaminase that act on RNA 2 (hADAR2) protein” in lines 2-3. There is insufficient antecedent basis for this limitation in the claim and it is unclear from the claims and the specification as to the specific amino acid sequence having at least 97% sequence identity to a human adenosine deaminase that act on RNA 2 (hADAR2) protein” to which the limitation refers. It is suggested that applicant clarify the meaning of the noted phrase.
Claim 1 (claims 4, 8, 11-14, 17, and 396-400 dependent therefrom) is confusing in the recitation of “wherein said hADAR2 consists of E488Q and D619G mutations and one or more of the mutations selected from…” because hADAR2 is not known in the art to consist of the recited mutations. It appears applicant intended for “hADAR2” to be “engineered protein” in the phrase “wherein said hADAR2 consists of E488Q and D619G mutations and one or more of the mutations selected from…” and applicant may consider amending claim 1 to replace “hADAR2” with “engineered protein” in the noted phrase. In the interest of advancing prosecution, the recitation of “wherein said hADAR2 consists of E488Q and D619G mutations and one or more of the mutations selected from…” in claim 1 is interpreted as meaning “wherein said engineered protein consists of E488Q and D619G mutations and one or more of the mutations selected from…”
Claim 399 (claim 400 dependent therefrom) recites the limitation “the composition of claim 17.” There is insufficient antecedent basis for this limitation in the claim. Applicant may consider amending claim 17 to replace “composition” with “system.”
Claim Rejections - 35 USC § 112(a)
The rejections of claims 1, 4, 8, 11-14, and 17 under 35 U.S.C. 112(a) for new matter and for failing to comply with the written description and enablement requirements are withdrawn in view of applicant’s amendment to claim 1.
Claims 1, 4, 8, 11-14, 17, and 396-400 are newly rejected under 35 U.S.C. 112(a) as failing to comply with the written description requirement. The claims 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 at the time the application was filed, had possession of the claimed invention. This is a new matter rejection.
MPEP § 2163.II.A.3.(b) states, “when filing an amendment an applicant should show support in the original disclosure for new or amended claims”. See also MPEP 714.02. MPEP § 2163.II.A.3.(b) further states, “[i]f the originally filed disclosure does not provide support for each claim limitation, or if an element which applicant describes as essential or critical is not claimed, a new or amended claim must be rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112, para. 1, as lacking adequate written description”. According to MPEP § 2163.I.B, “While there is no in haec verba requirement, newly added claim limitations must be supported in the specification through express, implicit, or inherent disclosure” and “The fundamental factual inquiry is whether the specification conveys with reasonable clarity to those skilled in the art that, as of the filing date sought, applicant was in possession of the invention as now claimed. See, e.g., Vas-Cath, Inc., 935 F.2d at 1563-64, 19 USPQ2d at 1117”.
Claim 1 has been amended to recite (in relevant part) “the amino acid sequence having at least 97% sequence identity to a human adenosine deaminase that act on RNA 2 (hADAR2) protein” in lines 2-3. According to applicant’s remarks at p. 8:
Applicant has amended claim 1 to recite "at least 97% sequence identity to a human adenosine deaminase that act on RNA 2 (hADAR2) protein" and "consists of" the specified mutations. The hADAR2 protein comprises 701 amino acids, as is well known in the art. At 97% sequence identity, up to 21 amino acid positions (3% of 701) may differ from the wildtype hADAR2 sequence. The claim recites E488Q and D619G as required mutations, plus one or more mutations selected from a group of 15 additional positions (V351G, S486A, T375S, S370C, P462A, N597I, L332I, I398V, K350I, M383L, S661T, S582T, V440I, S495N, K418E). In total, the claim encompasses 2-17 specified mutations (E488Q + D619G + 1 to 15 selected mutations), all of which are disclosed in paragraphs [0587]-[0640] and demonstrated in the working example. The specification inherently supports this claim limitation through the recitation of various mutations to the hADAR2 protein that exceed 21 amino acid positions as recited by the 97% threshold, and these mutations can be found throughout paragraphs [0587]-[0640]. The 97% threshold accommodates the full range of claimed mutation combinations (up to 17 mutations) while allowing minimal variation (1-4 amino acids) at positions outside the specified mutations. This limited additional variation accommodates conservative substitutions (e.g., similar hydrophobic residues, similar charged residues) or minor variations that do not affect the engineered protein's cytidine deaminase activity, while ensuring the claimed proteins retain the core structural identity and functional characteristics of hADAR2.
However, the applicant’s noted remarks fail to show support for the newly added limitation “the amino acid sequence having at least 97% sequence identity to a human adenosine deaminase that act on RNA 2 (hADAR2) protein” in claim 1. First, it is unclear as to how the 17 recited mutations in claim 1 provide descriptive support for variation of up to 21 mutations of the hADAR2 sequence. Second, the 17 recited mutations in claim 1 are specify both a specific amino acid position and a specific amino acid substitution at that position and fail to provide descriptive support for 17 mutations at any position within the sequence of hADAR2 with any other amino acid. Applicant is invited to show support for the claim 1 limitation “the amino acid sequence having at least 97% sequence identity to a human adenosine deaminase that act on RNA 2 (hADAR2) protein” in the original application. In the absence of descriptive support, the newly added limitation introduces new matter into the claims.
Claim Rejections - 35 USC § 102
Claims 1, 4, 8, 11-14, 17, and 396-400 are newly rejected under 35 U.S.C. 102(a)(2) as being anticipated by Zhang et al. (U.S. 2021/0163944 A1; with priority to at least January 21, 2019; cited on the attached Form PTO-892; hereafter “Zhang”).
As amended, claim 1 is drawn to an engineered protein having cytidine deaminase activity and comprising the amino acid sequence having at least 97% sequence identity to a human adenosine deaminase that act on RNA 2 (hADAR2) protein wherein said hADAR2 consists of E488Q and D619G mutations and one or more of the mutations selected from the group consisting of: V351G, S486A, T375S, S370C, P462A, N597I, L3321,1398V, K350I, M383L, S661T, S582T, V4401, S495N, and K418E, wherein the amino acid numbering of the mutation positions corresponds to the amino acid sequence of the hADAR2 protein.
Regarding claim 1, Zhang teaches a human ADAR2 with the mutations V351G, E488Q, and D619G (pp. 77-78, paragraph [0650]).
Regarding claims 4, 8, 11, 13, 17, 397, and 399, Zhang teaches a system comprising the modified ADAR or a nucleotide sequence encoding the modified ADAR, a catalytically inactive Cas13 protein or a nucleotide sequence encoding the catalytically inactive Cas13 protein, and a guide sequence capable of hybridizing with a target RNA sequence (pp. 81-82, paragraph [0681]).
Regarding claims 12, 14, 396, 398, and 400, Zhang teaches the system is a vector system for expression (paragraph [0681]) and teaches the components of the system are delivered to a cell via lipid nanoparticles (paragraph [0689]).
Therefore, Zhang anticipates claims 1, 4, 8, 11-14, 17, and 396-400 as written.
Conclusion
Status of the claims:
Claims 1, 4, 8, 11-14, 17, and 396-400 are pending.
Claims 1, 4, 8, 11-14, 17, and 396-400 are rejected.
No claim is in condition for allowance.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DAVID J STEADMAN whose telephone number is (571)272-0942. The examiner can normally be reached Monday to Friday, 7:30 AM to 4:00 PM.
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/David Steadman/Primary Examiner, Art Unit 1656