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/Restriction/Claims
Applicant’s election with traverse of Group I (Claims 1-4, 6 and 40) in the reply filed om 1/14/2026 is acknowledged.
Applicant’s traversal is on the grounds that group I shares the common technical features with Groups II, III, IV, V and VI and can be examined together without undue burden. This is not found persuasive because the common technical feature was known in the art at the time of the invention, Briefly, Leonard describes a plasmid and extracellular vesicle thereof comprising an expression cassette encoding a fusion protein comprising CD63 and at least one cargo RNA with specific embodiments to RNA-motifs that bind the fusion protein with additional functional RNA sequences like sgRNAs (Leonard, para 37, 39). As the common technical feature was known in the art at the time of the invention, this cannot be considered a common special technical feature that would otherwise unify the groups. Furthermore, the search and examination of methods (Groups III and IV) is not coextensive with the search for compositions (Group I, II, V and VI), since the methods have manipulative steps that the compositions don’t have, and are evaluated differently under certain statues (i.e. 35 U.S.C 101 and 112 in particular). Accordingly, unity of invention is lacking and the requirement is still deemed proper and is therefore made FINAL.
Claims 1-4, 6, 14-17, 19, 21, 23-24, 28-29, 35 and 40-43 are pending. Claims 14-17, 19, 21, 23-24, 28-29, 35 and 41-43 are currently withdrawn from further consideration pursuant to 37 CFR 1.142 (b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claims 1-4, 6 and 40 are the subject of the present Official action.
Priority
Applicant’s claim for the benefit of a prior-filed application PRO 63/148,872 and 371 of PCT/US2022/016053 filed on 2/12/2021 and 2/11/2022, respectively, under 35 U.S.C 119(e) or under 35 U.S.C 120, 121 or 365(c) is acknowledged.
Accordingly, the effective priority date of the instant application is granted as 2/12/2021.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 12/11/2024, 7/18/2025 and 1/14/2026 were received. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement was considered by the examiner.
Claim Interpretation
The claims describe a plasmid system comprising several expression plasmids and an envelope plasmid. It is emphasized that the current claim language broadly encompasses ANY delivery system which comprises the plasmid system including both extracellular vesicles, lentiviral vector systems among others.
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 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.
Claims 1-4 and 40 are rejected under 35 U.S.C. 103 as being unpatentable over Lu et al. WO 2019/213257, published 11/7/2019 (hereinafter Lu) in view of Leonard et al. US 2020/0390700, published 12/17/2020 (hereinafter Leonard).
Claim 1: Lu describes lentivirus-like particles for delivering a plasmid system comprising a first mammalian expression plasmid comprising a eukaryotic promoter operably linked to a nucleic acid sequence comprising a CRISPR-associated endonuclease and a gRNA comprising at least one aptamer coding sequence (Lu, abstract and para 7, 9, 11). Lu further describes a second mammalian expression plasmid comprising a eukaryotic promoter operably linked to a nucleic acid sequence encoding a modified viral protein that is a fusion protein with an aptamer-binding protein (Lu, para 62, 74, 121, 143). Lu does not expressly describe that the aptamer binding protein is a fusion with CD63 in the second expression plasmid which binds to the aptamer coding sequence of the fist expression plasmid.
Claim 2: Lu describes the system further comprising an envelope plasmid which encode vesicular stomatis virus G (VSV G) protein (Lu, para 117 and 229).
Claim 3: Lu provides a preferred embodiment towards the CRISPR-associated endonuclease being a Cas9 protein (Lu, para 1 and 99).
Claim 4: Lu describes provides a preferred embodiment towards catalytically impaired CRISPR-associated endonucleases like dCas9 (Lu, para 102).
Claim 20: Lu describes cells containing the expressed plasmid system (Lu, para 105, 120).
Claim 1: Leonard describes a secreted extracellular vesicle that contains an engineered targeting membrane fusion protein (Leonard, para 3-4). Leonard describes targeting membrane fusion proteins comprising CD63 and at least one cargo RNA with specific embodiments to RNA-motifs that bind the fusion protein with additional functional RNA sequences like sgRNAs (Leonard, para 34, 37, 39). Leonard states that CD63 fusions significantly enhance cargo loading into exosomes (Leonard, para 112).
It would have been prima facie obvious to one of ordinary skill in the art to create a fusion protein comprising a CD63 as described by Leonard and at least one aptamer binding protein targeting the CRISPR expression plasmid as described by Lu. It would have been a matter of combining prior art elements according to known methods to yield predictable results since Leonard states that CD63 fusions significantly enhance cargo loading into exosomes (Leonard, para 112). Thus, one of ordinary skill would have been motivated to make this combination in order to enhance cargo loading into the lentivirus-like particles described by Lu. This is particularly important given that Lu describes loading multiple plasmids into a single lentivirus-like particles. One would have a reasonable expectation of success given that CD63- ABP systems can direct specific plasmids or RNA into exosomes via an active packing mechanism which is particularly advantageous. Accordingly, in the absence of evidence to the contrary, one of ordinary skill in the art would have considered claims 1-4 and 40 to have been prima facie obvious to at the time the invention was made.
Claims 1-4, 6 and 40 are rejected under 35 U.S.C. 103 as being unpatentable over Lu (supra) in view of Leonard (supra) as applied to claims 1-4 and 40 above in further view of Sun et al. "Recent advances of genome editing and related technologies in China." Gene Therapy 27.7 (2020): 312-320 (hereinafter Sun). A description of claims 1-4 and 40 can be found above. Neither Lu nor Leonard describes a first expression plasmid encoding for an adenosine base pair editor (ABE) which is fused to a catalytically impaired CRISPR endonuclease.
Claim 6: Sun describes the use of base editing for generating precise nucleotide changes in target DNA without introducing DNA double stranded breaks (Sun, pg 314). Sun describes the use of adenine base editors capable of converting A-T and G-C by fusing a catalytically impaired dCas9 to an adenine deaminase (Sun, pg 314). Sun describes the advantages of a system in achieving targeted DNA editing without double stranded breaks and reduced indels (Sun, pg 314).
It would have been prima facie obvious to one of ordinary skill in the art to deliver an ABE fused to a dCas9 as described by Sun using the plasmid delivery system described by Lu in view of Leonard. It would have been a matter of combining prior art elements according to known methods to yield predictable results since adenine base editors are known in the art and are able to in achieving targeted DNA editing without double stranded breaks and reduced indels. One of ordinary skill would have been motivated to make this combination in order to deliver ABEs using the lentivirus-like particles described by Lu given their low toxicity and high carrying capacity, especially when utilizing the CD63 fusions disclosed by Leonard. One would have a reasonable expectation of success given the high editing efficiency of ABEs and programable targeting of ABEs to gene targets. Accordingly, in the absence of evidence to the contrary, one of ordinary skill in the art would have considered the claimed invention have been prima facie obvious to at the time the invention was made.
Conclusion
No claims allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Dr. ALEXANDER NICOL whose telephone number is (571)272-6383. The examiner can normally be reached on M-F 8-5 EST.
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Alexander Nicol
Patent Examiner
Art Unit 1634
/ALEXANDER W NICOL/Examiner, Art Unit 1634