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 .
Claim Status
Claim listing filed on November 12, 2025 is pending. Claims 2-3, 5, 7-11, 13-28, 32-49, 51, and 69 are canceled. Claims 1, 4, 6, 12, 29-31, 50, and 52-62 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected inventions or species; election made without traverse in the reply filed on June 4, 2025. Claims 63, 66-68, 70, 74, and 78-80 are amended. Claims 63-68 and 70-81 are examined upon their merits.
Information Disclosure Statement
The information disclosure statement filed on 11/12/2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Withdrawn Objections and Rejections
Applicant’s cancelation of Claims 51 and 69 have rendered all previous rejections directed to these claims moot.
The rejection of claims 63-68 and 70-81 under 35 U.S.C. 112(b) as being indefinite is withdrawn in view of Applicant’s amendments. In particular, amended Claim 63 recites a method of reducing the immune response to a composition comprising a circular RNA molecule wherein the immune response is reduced as compared to a composition prepared in the same manner comprising the same circular RNA molecule without modification. The relative terminology is no longer indefinite, because the reduction is in comparison to a circular RNA molecule without modification. “Reduce” is interpreted to encompass any reduction, even a statistically insignificant change, wherein “immune response” can be quantified by any means known in the art prior to the time of filing.
The rejection of claims 63-68 and 70-81 under 35 U.S.C. 112(a) as failing to comply with the enablement requirement is withdrawn in view of Applicant’s amendments. Amended Claim 63 specifically defines wherein the reduced immune response is in comparison to a composition prepared in the same manner comprising the same circular RNA molecule without modification. Examiner interprets this to mean that all conditions are held constant except for the addition of the m6A, pseudouridine, or inosine modifications. Therefore, the unpredictability in the art surrounding the innate immunogenicity of circular RNA is moot, because the claims are directed to a reduction in immune response with a matched control. As Applicant states in the remarks filed 11/12/2025, the issue of potential contaminants in the composition is moot because the two compositions are prepared in the same manner, and one of ordinary skill could reasonably expect that the reduced immune response is due to the nucleoside modification (page 11).
Claim Rejections - 35 USC § 112 (New, necessitated by amendment)
Claim 78 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 78 recites the limitation "the reduced immunogenicity" in line 1. There is insufficient antecedent basis for this limitation in the claim. For the purpose of compact prosecution, Claim 78 is interpreted as “wherein the reduced immune response is an innate and/or adaptive immune response.” Appropriate action is required.
Note, “delivered” in Claims 79-80 is interpreted to be synonymous with “administering” in Claim 63.
Claim Rejections - 35 USC § 102 (New, necessitated by amendment)
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 63-68, 70-75, and 78-80 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Kahvejian et al. WO 2020/023655 (filed July 24, 2019).
In regard to Claims 63-65 and 78-79, Kahvejian teaches that circular RNA comprising modified nucleotides pseudouridine and m6A in place of the standard unmodified nucleotides uridine and adenosine had reduced immunogenicity as compared to unmodified RNA (paragraphs [0483]-[0485]). Specifically, the level of protein scaffolding to immune proteins that activate innate immune response genes was monitored in BJ cells transfected with unmodified circular RNA or modified circular RNA (paragraph [0488]). Levels of immune related genes from BJ cells transfected with modified circular RNAs showed reduced levels of MDA5, OAS, and IFN-beta expression as compared to unmodified circular RNA transfected cells, indicating reduced protein scaffolding between modified circular RNAs and immune proteins that activate immunogenic related genes (paragraph [0489] and Fig. 10). The modified and unmodified circular RNAs were prepared in the same manner (paragraph [0485]). Kahvejian further teaches that the circular RNA can comprise an inosine modification which can attenuate an immune response (paragraph [0289]). The circular RNA can be included in a pharmaceutical composition and administered to a subject in need thereof such as a human (paragraph [0311]).
In regard to Claims 66-68, Kahvejian teaches that the circular RNA can include from about 1% to about 100% modified nucleotides (paragraph [0290]). For example, circular RNA can be completely modified or partially modified (paragraph [0485] and Fig. 9A).
In regard to Claims 70-75, Kahvejian teaches that the circular RNA can comprise an IRES (paragraph [0021] page 8). The circular RNA can include a sequence encoding a protein such as a therapeutic protein comprising a viral antigen, a tumor antigen, a bacterial antigen, a cytokine, an antibody, a chimeric antigen receptor, or a ligand or a receptor (paragraph [0186]). The sequence to be encoded can be linked to the IRES (Fig. 9A).
In regard to Claim 80, Kahvejian teaches that the circular RNA can be administered by a nanoparticle (paragraph [0311]).
Therefore, Claims 63-68, 70-75, and 78-80 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Kahvejian.
Claim Rejections - 35 USC § 103
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 63-68, 70-77, and 78-80 are rejected under 35 U.S.C. 103 as being unpatentable over Kahvejian et al. WO 2020/023655 (filed July 24, 2019) in view of Pandolfi et al. US 2017/0298347.
The teachings of Kahvejian as they apply to Claims 63-68, 70-75, and 78-80 are outlined in the 102 rejection above. Kahvejian fails to teach wherein the pharmaceutical composition comprising the modified circular RNA is administered intravenously (Claims 76-77). Note, in Claims 76-77 it is interpreted that “the modified circular RNA molecule” refers to the composition comprising the modified circular RNA molecule defined in Claim 63.
Pandolfi teaches novel modified circular RNAs (abstract) that can be formulated as pharmaceutical compositions suitable for intravenous administration (paragraph [0197]).
Based on these teachings, it would have been prima facie obvious to one of ordinary skill in the art, at the time the invention was made, to adapt the pharmaceutical composition comprising the modified circular RNA taught by Kahvejian to be suitable for intravenous administration as taught by Pandolfi. Pandolfi teaches the proof-of-concept that modified circular RNAs can be administered intravenously. The motivation to administer the circular RNA of Kahvejian intravenously is for ease of administration and physician/patient compliance as intravenous administration is routine medical practice.
Claims 63-68, 70-75, and 78-81 are rejected under 35 U.S.C. 103 as being unpatentable over Kahvejian et al. WO 2020/023655 (filed July 24, 2019) in view of Rosenkranz et al. Russ. Chem. Bull. 2015.
The teachings of Kahvejian as they apply to Claims 63-68, 70-75, and 78-80 are outlined in the 102 rejection above. Kahvejian fails to teach wherein the nanoparticle is polyethylenimine (PEI) (Claim 81).
Rosenkranz teaches that PEI nanoparticles are used to deliver RNA molecules (title and abstract).
Based on these teachings, it would have been prima facie obvious to one of ordinary skill in the art, at the time the invention was made, to adapt the nanoparticle delivery system comprising the modified circular RNA taught by Kahvejian to specifically be a PEI nanoparticle as taught by Rosenkranz. The motivation to use a PEI nanoparticle is because it is one of the most successful and efficient designs for delivering nucleic acids into cells, more efficient than most other known methods (Rosenkranz page 2750, paragraph 2).
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 SARAH COOPER PATTERSON whose telephone number is (703)756-1991. The examiner can normally be reached Monday - Friday 8:00am - 5:00pm EST.
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/SARAH COOPER PATTERSON/Examiner, Art Unit 1675
/JEFFREY STUCKER/Supervisory Patent Examiner, Art Unit 1675