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 .
Amendments
In the reply filed 7/06/2026, Applicant has amended Claims 74, 77, 78, and 99, cancelled claims 50-52, 54-60, 75-76, and 83-94, and added a new claim, Claim 100.
Claims 61-62, 66-67, 74, 77-82, and 95-100 are under consideration.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 7/06/2026 was filed after the mailing date of the non-final Office action on 3/27/2026. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Withdrawn 35 USC § 112(a)
The prior rejection of Claims 61-62, 66-67, 74, 77-82, and 95-99 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112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement is withdrawn in light of Applicant’s amendments of Claim 74 to remove the unsupported negative limitation.
Withdrawn 35 USC § 101
The prior rejection of Claims 74, 79, 81, and 95-97 under 35 U.S.C. 101 because the claimed invention is directed to a natural product without significantly more. The claim(s) recite(s) naturally occurring immunogenic circular RNA is withdrawn in light of Applicant’s amendments of Claim 74 to distinguish it from a natural product by conjugating it to a targeting ligand.
Withdrawn 35 USC § 102
The prior rejection of Claims 61-62, 66-67, 74, 79-80, and 96-98 under 35 U.S.C. 102(a)(1)/(a)(2) as being anticipated by Ares et al., (US 5,773,244, filed 5/1/1995, patented 6/30/1998, see IDS filed 2/28/2023), as evidenced by Chen et al. (Mol Cell, 67, 228-238, see IDS filed 2/28/2023) is withdrawn in light of Applicant’s amendment of Claim 74 to limit the circular RNA is conjugated targeting ligand, which is a limitation Ares does not anticipated.
The prior rejection of Claims 74, 79-81, and 95-99 under 35 U.S.C. 102(a)(1)/(a)(2) as being anticipated by Sarnow et al., (US 5,766,903, patented 6/16/1998, see IDS filed 2/28/2023), as evidenced by Chen et al. (Mol Cell, 67, 228-238, see IDS filed 2/28/2023) is withdrawn in light of Applicant’s amendment of Claim 74 to limit the circular RNA is conjugated targeting ligand, which is a limitation Sarnow does not anticipated.
The prior rejection of Claims 74, 79 and 96-97 under 35 U.S.C. 102(a)(2) as being anticipated by Mutzke et al., (WO 2016/165825, filed 4/13/2016, published 10/20/2016) is withdrawn in light of Applicant’s amendment of Claim 74 to limit the circular RNA is conjugated targeting ligand, which is a limitation Mutzke does not anticipated.
Withdrawn 35 USC § 103
The prior rejection of Claims 77-78, and 99 under 35 U.S.C. 103 as being unpatentable over Mutzke et al., (WO 2016/165825, filed 4/13/2016, published 10/20/2016) is withdrawn in light of Applicant’s amendment of Claim 74 to limit the circular RNA to being conjugated targeting ligand
The prior rejection of Claim 82 under 35 U.S.C. 103 as being unpatentable over Mutzke et al., (WO 2016/165825, filed 4/13/2016, published 10/20/2016), in view of Nelson et al., (WO 2016/01222, filed 7/16/2015, published 1/21/2016, see IDS filed 2/28/2023) is withdrawn in light of Applicant’s amendment of Claim 74 to limit the circular RNA to being conjugated targeting ligand
New 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.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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 61, 66, 74, 77-82, and 95-100 are rejected under 35 U.S.C. 103 as being unpatentable over Hoge et al., (US2016/0194368, filed 9/03/2014, published 7/07/2016)
In regard to claim 74, Hoge teaches a circular RNA (circRNA) that is:
Conjugated to a targeting ligand ([0056-0057] Conjugates and Combinations, [0564-0576] Conjugates);
Comprises an IRES ([0047], [0166] IRES Sequences, [0200], [0272], see Fig. 1); and
Comprises a nucleic acid sequence encoding an immunogenic protein ([0111-0113] Vaccines, [0927-0932] Activation of the Immune Response: Vaccines).
However, Hoge does not claim nor provide a preferred embodiment of an immunogenic circular RNA conjugated to a targeting ligand, an IRES, and encoding immunogenic protein for vaccination purposes.
Nevertheless, it would have been obvious to one having ordinary skill in the art at the time the invention was filed to have prepared said circular RNA because each of the individual elements of the instant claims are independently presented by Hoge as embodiments and are taught that they can be combined in various embodiments; therefore a combination of all the elements into a single embodiment would be apparent to an artisan skilled in vaccine gene therapy in light of the Supreme Court’s KSR decision (see MPEP 2143 Exemplary Rationale (A)). Regarding the rationale for combining prior art elements according to known methods to yield predictable results, all of the claimed elements were known in the prior art and one skilled in the art could have combined the element as claimed by known methods with no change in their respective functions, and the combination would have yielded predictable results to one of ordinary skill in the art at the time of filing the invention. Each of the elements (circular RNAs, conjugation to targeting ligands for cell specific targeting, IRES for ribosomal binding and translation of the encoding nucleic acid, and nucleic acids encoding an immunogenic protein for vaccines) are taught by Hoge, and further they are taught in various combinations and are shown to be used in a method for producing the immunogenic circular RNA for vaccination purposes that is conjugated to a targeting ligand, and comprises an IRES operably linked to a nucleic acid encoding an antigenic peptide. It would have been therefore predictably obvious to use a combination of these elements in said composition.
In regard to claims 61 and 66, Hoge teaches that the circRNAs can be made by self-splicing of a Group I intron [0006, 0190, 0264].
In regard to claim 77, Hoge teaches the circRNA encodes an antigen peptide derived from a bacterium, virus, or protozoan that can be used as an anti-infective vaccine [0931, 0113].
In regard to claim 78, Hoge teaches the circRNA encodes a tumor antigen that can be used as an oncology vaccine [0932, 0949, 0113].
In regard to claims 79, 97, and 99, as stated supra, Hoge teaches the circRNA is a vaccine that encodes a therapeutic polypeptide antigen, which is to be administered prophylactically for treating a disease.
In regard to claim 80, Hoge teaches the circRNA comprises modified nucleosides to activate the innate immune response thereby acting as an adjuvant when combined with polypeptide vaccines [0929].
In regard to claims 81 and 95, Hoge teaches the composition further comprises a lipid-nanoparticle [0370-0389].
In regard to claim 82, Hoge teaches the composition further comprises an antiviral agent, antibiotic, antifungal, antiparsitic or chemotherapeutic [0608, 0770, 0773 0776, 0894, 0889-0890, 0898, 0901, 0903]
In regard to claim 96, Hoge teaches the composition further comprises a delivery vehicle [0328, 0339].
In regard to claim 98, Hoge teaches the circRNA is formulated to be administered as naked ([0699-0700] Naked Delivery).
In regard to claim 100, Hoge teaches the targeting ligand is peptide or protein [0056, 0564, 0570-0572].
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Claims 62 and 67 are rejected under 35 U.S.C. 103 as being unpatentable over Hoge et al., (US2016/0194368, filed 9/03/2014, published 7/07/2016), in view of Ares et al., (US 5,773,244, filed 5/1/1995, patented 6/30/1998, see IDS filed 2/28/2023)
As stated supra, Hoge suggests circular RNA conjugated to a targeting ligand, with an IRES operably linked to an antigenic peptide.
In regard to claims 62 and 67, although Hoge teaches that the circRNAs can be made by the self-spicing of a Group I intron [0190, 0264], they are silent to the arrangement of the self-splicing elements and using a T4 phage Group I intron in particular.
Nevertheless, Hoge cites the prior art of Ares et al. (US 5,773,244) as incorporated by reference [0006, 0194].
In regard to claims 62 and 66, Ares teaches a circular RNA generated by splicing of a Group I self-splicing intron from the bacteriophage T4 thymidylate synthase (Td) gene from a recombinant nucleic acid comprising in a 5’ to 3’ order the 3’ Td intron with 3’ splice site, a nucleic acid sequence of the circular RNA, and the 5’ Td intron with 5’ splice site (cols 11-14, Figs. 1-6).
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art at the time of filing to have prepared the composition comprising a circular RNA made by a Group I self-splicing intron as taught by Hoge, and choose the Group I self-splicing intron from the bacteriophage T4 thymidylate synthase (Td) gene made from a recombinant nucleic acid comprising in a 5’ to 3’ order the 3’ Td intron with 3’ splice site, a nucleic acid sequence of the circular RNA, and the 5’ Td intron with 5’ splice site as taught by Ares with a reasonable expectation of success. The ordinary skilled artisan would have been motivated to do for several reasons. First, as stated supra, Hoge incorporates by reference the teachings of Ares, thus it would have been obvious to one of ordinary skill to turn to Ares for an enabling disclosure for how to make the circular RNA by a Group I self-splicing intron. Furthermore, Ares teaches the Group I self-splicing intron from Td gene allows efficient production of circular RNA in vitro and in cells and has considerable advantages over existing techniques (col 1, Background of the Invention, col 10, 2nd para., col 17, 2nd to 4th para.)
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
RESPONSE TO ARGUMENTS
Applicant's arguments filed on 3/27/2026 are acknowledged.
Applicant argues that the cited prior art does not teach a circular RNA conjugated to a targeting ligand, and IRES.
Applicant's arguments have been fully considered and they are found persuasive.
However, the prior art of Hoge has been applied, which makes predictable obvious making and using a circular RNA comprising a conjugated targeting ligand, IRES, and encoding an immunogenic protein.
Withdrawn Double Patenting
The prior rejection of Claims 74, 77, 79, 81 and 95-99 on the grounds of nonstatutory double patenting over claims 1-12 of U.S. Patent No. 11,560,567 (Chang et al., Patented 1/24/2023), in view of Sarnow et al., (US 5,766,903, patented 6/16/1998, see IDS filed 2/28/2023) is withdrawn in light of Applicant’s amendment of Claim 74 to limit the circular RNA to being conjugated targeting ligand
The prior provisional rejection of Claims 74, 77-79 and 96-99 on the grounds of nonstatutory double patenting as being unpatentable over claims 1, 4, 6 of copending Application No. 17/635,760 is withdrawn in light of Applicant’s amendment of Claim 74 to limit the circular RNA to being conjugated targeting ligand, as well as the cancellation of copending claims.
The prior provisional rejection of Claims 61, 66, 74, 77, 79-81, and 95-99 on the grounds of nonstatutory double patenting as being unpatentable over claims 42-74 of copending Application No. 18/340,582, in view of Sarnow et al., (US 5,766,903, patented 6/16/1998, see IDS filed 2/28/2023) is withdrawn in light of Applicant’s amendment of Claim 74 to limit the circular RNA to being conjugated targeting ligand
The prior provisional rejection of Claims 74, 78-79, and 96-99 on the grounds of nonstatutory double patenting as being unpatentable over claims 1, 6, and 29 copending Application No. 18/847,095, in view of Sarnow et al., (US 5,766,903, patented 6/16/1998, see IDS filed 2/28/2023) is withdrawn in light of Applicant’s amendment of Claim 74 to limit the circular RNA to being conjugated targeting ligand
Conclusion
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 extension fee 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 date of this final action.
No claims are allowed.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ARTHUR S LEONARD whose telephone number is (571)270-3073. The examiner can normally be reached on Mon-Fri 9am-5pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James Doug Schultz can be reached on 571-272-0763. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/ARTHUR S LEONARD/Examiner, Art Unit 1631
Prosecution Insights