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 .
Applicant’s amendments and arguments of May 19, 2026, are entered.
Claims 17 and 21-22 have been amended.
Claims 18-20 and 23-24 have been canceled.
No new claims have been added.
Information Disclosure Statement
The information disclosure statement(s) (IDS) submitted on May 19, 2026, was filed before the mailing of the Final Office Action on July 25, 2026. The Non-Patent Literature is in compliance with the provisions of 37 CFR 1.97 and are being considered by the examiner.
Drawings
Applicant submitted replacement drawings that overcome the previous objections. Therefore, the objection to the drawings are withdrawn.
Claim Rejections - 35 USC § 112(a)
In light of Applicant’s amendments and unless otherwise noted, the rejections under 35 U.S.C. §112(a) for written description are withdrawn.
Claim Rejections - 35 USC § 112(b)
In light of Applicant’s cancellation of claim 20, the rejection under 35 U.S.C. §112(b) for being indefinite is withdrawn.
Claim Rejections – 35 USC § 103
In light of Applicant’s amendments, the previous rejection claims 17-24 under 35 U.S.C. §103 is withdrawn.
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.
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.
Claims 17 and 21-22 are newly rejected under 35 U.S.C. §103 as being unpatentable over Kim et al. [Concurrent progress of reprogramming and gene correction to overcome therapeutic limitation of mutant ALK2-iPSC, Nature Experimental & Molecular Medicine, 2016], in view of Liu et al. [WO 2020 236982 A1, 2020], in view of Marcussen & Grogan (Hereinafter Marcussen) [US 2017 0159056 A1].
For claim 17, Kim et al. discloses a recombinant gene editing complex: comprising (i) a single guide RNA (sgRNA) that specifically hybridizes to a target nucleic acid sequence of an ACVR1 gene [Abstract, Reprogramming factors and gene editing tools ¶ 1]. However, Kim does not teach a target nucleic acid comprising an ACVR1-encoding target sequence and a protospacer adjacent motif consisting of SEQ ID NO: 51, wherein the sgRNA of (i) is hybridized to the target nucleic acid. Additionally, Kim et al. does not teach a first rAAV particle encoding a first recombinant gene editing protein or fragment thereof; and a second rAAV particle encoding a second recombinant gene editing protein or fragment thereof.
For the limitation related to target nucleic acid comprising an ACVR1-encoding target sequence and a protospacer adjacent motif consisting of SEQ ID NO: 51, Marcussen discloses a nucleic acid sequence, SEQ ID NO: 1, that shares an identical contiguous core nucleotide sequence with the only difference being the presence of additional flanking nucleotides in the prior art of Marcussen versus the unspecified nucleotides, i.e. “N”, at the corresponding positions in Applicant’s claimed sequence. However, the overlapping region exhibits 100% identity.
With respect to the protospacer adjacent motif, Liu et al. discloses a protospacer adjacent motif with a Cas9 editing complex [¶ 0073]. Liu et al. further discloses a dual-vector rAAV system where two recombinant adeno-associated viral particles each contain a portion of a gene editing construct [¶ 0004]. Liu et al. specifically discloses the first rAAV particle encodes one recombinant gene editing protein component, and the second rAAV particle encodes the complementary recombinant component necessary to reconstitute the complete gene editing complex in the target cell [Id], where the first recombinant editing complex is a Cas9-based adenine base editor N-terminus portion and the second recombinant editing complex is a Cas9-based adenine editor C-terminus are divided.
Here, it would have been prima facie obvious to a person of ordinary skill in the art prior to the filing of the claimed invention to modify the systems and methods of Kim et al. that discloses a gene editing complex, e.g. CRISPR Cas9 system, that uses a sgRNA targeting a specific area in the ACVR1 gene with the teachings of both Marcussen that discloses an antisense oligonucleotide sequence designed for targeting a mutant AVCR1 gene with the additional teachings of Liu et al. that discloses a dual-vector system utilizing Cas9 adenine base editing where the Cas9 adenine base editor is divided between both an N-terminus and C-terminus portion that further includes a protospacer adjacent motif. Given this, there is a reasonable expectation of success that a person of ordinary skill in the art would have recognized the teachings of Kim et al. and combined them with the teachings of Marcussen in order to target an ACVR1 gene using the nucleic acid sequence disclosed by Marcussen where the Cas9 editing complex could then be employed using a dual-vector rAAV system as taught by Liu et al. allowing for efficient in vivo delivery of the Cas9 editing system disclosed by Kim et al. modified with the nucleic acid sequence of Marcussen given that these references address compatible gene editing systems and rAAV dual-vector strategies were known to reconstitute full-length editing proteins in target cells.
For claim 21 where the first and second rAAV particles are either an rAAV9 capsid or an AAV6.2 capsid, Liu et al. discloses that the AAV9 particles were used [¶ 00505].
For claim 22 where the recombinant gene editing complex of claim 18 for the N-terminus and C-terminus ABE constructs are divided by using a trans-splicing intein, Liu et al. teaches the use of trans-splicing inteins to cytosine base editors and adenine base editors to be divided into halves that are each smaller than the AAV packaging size [¶ 00498].
Here, it would have been prima facie obvious to a person of ordinary skill in the art prior to the filing of the claimed invention to modify the systems and methods of Kim et al. that discloses a gene editing complex, e.g. CRISPR-Cas9 system, that uses a sgRNA targeting a specific area in the ACVR1 gene with both Marcussen that discloses an antisense oligonucleotide sequence designed for targeting a mutant AVCR1 gene with the additional teachings of Liu et al. that discloses the use of a dual-vector rAAV delivery system based off of the Cas9 system that includes adenine base editors for the N-terminus and C-terminus portions where the Cas9 system contains a protospacer adjacent motif, and the N-terminus and C-terminus adenine based editor is divided by a trans-splicing intein. Because of this, there is reasonable expectation of success that a person of ordinary skill in the art would combine Kim et al. with the additional teachings of Liu et al. allowing a dual-vector Cas9 gene editing complex that contains an adenine base editor that has been divided into a N-terminus and C-terminus adenine base editor for packaging purposes that is capable of targeting the ACVR1 gene.
The Supreme court has acknowledged:
When a work is available in one field of endeavor, design incentives and other market forces can prompt variations of it, either in the same field or a different one. If a person of ordinary skill can implement a predictable varition..103 likely bars its patentability…if a technique has been used to improve one device, and a person of ordinary skill in the art would recognize that it would improve similar devices in the same way, using the technique is obvious unless its actual application is beyond that person’s skill. A court must ask whether the improvement is more than the predictable use of prior-art elements according to their established functions…
…the combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results (see KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 U.S. 2007) emphasis added.
In KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398 (2007), the Supreme Court reaffirmed "the conclusion that when a patent 'simply arranges old elements with each performing the same function it had been known to perform' and yields no more than one would expect from such an arrangement, the combination is obvious." Id. at 417 (quoting Sakraida v. Ag Pro, Inc., 425 U.S. 273,282 (1976)). The Supreme Court also emphasized a flexible approach to the obviousness question, stating that the analysis under 35 U.S.C. § 103 "need not seek out precise teachings directed to the specific subject matter of the challenged claim, for a court can take account of the inferences and creative steps that a person of ordinary skill in the art would employ." Id. at 418; see also id. at 421 ("A person of ordinary skill is... a person of ordinary creativity, not an automaton.").
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary
Conclusion
No claims 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 JOHN DAVID MOORE whose telephone number is (703)756-1887. The examiner can normally be reached M-F 8-5.
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/JOHN DAVID MOORE/Examiner, Art Unit 1638
/Tracy Vivlemore/Supervisory Primary Examiner, Art Unit 1638
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