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 .
Claims 1-19 and 40 are pending in the application.
Applicant’s amendment to the claims, filed March 19, 2026, is acknowledged. This listing of the claims replaces all prior versions and listings of the claims.
Applicant’s amendment to the specification, filed March 19, 2026, is acknowledged.
Applicant’s remarks and declaration under 37 CFR 1.132 (hereafter “Hazra Declaration”) filed March 19, 2026 in response to the non-final rejection filed December 19, 2025 are acknowledged and have been fully considered.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Restriction/Election
In response to a requirement for restriction/election filed September 11, 2025, applicant elected without traverse the species of NEIL2 peptide is administered by inhalation (species election A), the species of lung cell targeting segment has an amino acid sequence of SEQ ID NO: 2 (species election B), and the species of virus is from the Coronaviridae family (species election C) in the reply filed November 11, 2025.
Applicant requests changing species election A to the species of NEIL2 peptide is administered intranasally and changing species election B to the species of lung cell targeting segment has an amino acid sequence of SEQ ID NO: 9. Applicant’s requests are acknowledged, however, applicant has received an action on the merits for the originally elected species and the search and examination has not been extended to the non-elected species requested by applicant.
Claims 3 and 10 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected species, there being no allowable generic or linking claim.
Claims 1, 2, 4-9, 11-19, and 40 are being examined on the merits.
Information Disclosure Statement
The examiner has previously considered the information disclosure statement (IDS) filed July 25, 2023, however, a copy of the initialed and signed IDS has not been filed in the application. A copy of the initialed and signed IDS filed July 25, 2023 is attached to this Office action.
Specification/Informalities
The objection to the specification for the use of trade names or marks “triton” and “pluronic” is withdrawn in view of applicant’s amendments to the specification to include the symbol “™” following the trade names or marks.
Claim Objections
The objection to claims 1, 2, 4-7, 17-19, and 40 is withdrawn in view of applicant’s amendment to claim 1 to recite the entire phrase for which the abbreviation “NEIL2” is used.
Claim Rejections - 35 USC § 112(b)
The rejection of claims 5, 6, 8, 9, and 40 under 35 U.S.C. 112(b) is withdrawn in view of applicant’s amendments to claims 5 and 6 to recite “The method of claim 1,” amendment to claim 5 to recite “wherein the functional fragment has DNA glycosylase activity,” amendment to claim 8 to depend from claim 7, and amendment to claim 40 to delete the phrase “wherein the NEIL2 protein levels are below a reference level for NEIL2 protein.”
The rejection of claim 17 under 35 U.S.C. 112(b) as being indefinite in the recitation of “about” is maintained for the reasons of record.
RESPONSE TO REMARKS: Applicant argues the claim has been clarified to place the claim in condition to overcome the indefiniteness rejection.
Applicant’s argument is not found persuasive. The previous version of claim 17 recited two occurrences of “about” and only a single occurrence of “about” has been deleted from the claim.
Claim Rejections - 35 USC § 112(a)
The rejection of claim 40 under 35 U.S.C. 112(a) as failing to comply with the written description requirement is maintained for the reasons of record.
RESPONSE TO REMARKS: In summary, applicant argues the specification provides sufficient disclosure to demonstrate possession of the method of claim 40.
Applicant’s arguments are not found persuasive. The examiner acknowledges the applicant’s cited disclosures of the specification, however, these disclosures are related to a correlation between relative low expression levels of NEIL2 RNA and COVID-19 severity. Claim 40 has been amended to remove the limitation “when the NEIL2 protein levels are below a reference level for NEIL2 protein” and claim 40 now broadly encompasses identifying a subject at risk for a virus induced dysregulation of inflammatory response based on any absolute and/or increased, decreased, or same relative protein level in any biological sample. As stated in the prior Office action, the specification and art of record fail to disclose even a single representative species of the claimed invention, the specification fails to provide guidance or direction regarding protein level(s) of NEIL2 from any biological sample that is/are indicative of being at risk for a virus induced dysregulation of inflammatory response, and there was unpredictability in correlating RNA and protein abundance. As such, one of skill in the art would reasonably conclude that the applicant was not in possession of the claimed invention. In this case, the specification at best describes a research plan for practicing the claimed method, however, a plan for practicing the claimed invention is not sufficient to show possession at the time of filing.
For these reasons, it is the examiner’s position that the specification fails to adequately describe the claimed invention.
The rejection of claim 40 under 35 U.S.C. 112(a) as failing to comply with the enablement requirement is maintained for the reasons of record.
RESPONSE TO REMARKS: In summary, applicant argues the specification provides sufficient disclosure to demonstrate possession of the method of claim 40.
Applicant’s arguments are not found persuasive. The examiner acknowledges the applicant’s cited disclosures of the specification, however, these disclosures are related to a correlation between relative low expression levels of NEIL2 RNA and COVID-19 severity. Claim 40 has been amended to remove the limitation “when the NEIL2 protein levels are below a reference level for NEIL2 protein” and claim 40 now broadly encompasses identifying a subject at risk for a virus induced dysregulation of inflammatory response based on any absolute and/or increased, decreased, or same relative protein level in any biological sample. Contrary to applicant’s position, in view of a detailed analysis of the Factors of In re Wands (set forth in the prior Office action), particularly that the specification and art of record fail to disclose even a single working example of the claimed invention, the specification fails to provide guidance or direction regarding protein level(s) of NEIL2 in a biological sample that are indicative of being at risk for a virus induced dysregulation of inflammatory response, and there was unpredictability in correlating RNA and protein abundance, it is the examiner’s position that the specification fails to make and use the full scope of the claimed invention without requiring undue experimentation.
Claim Rejections - 35 USC § 103
The rejection of claim 19 under 35 U.S.C. 103 as being unpatentable over Wilson et al. (US 2011/0110908 A1; cited on Form PTO-892 filed December 19, 2025; hereafter “Wilson”) in view of Li et al. (Cell. Mol. Life Sci. 72:2973-2988, 2015; cited on Form PTO-892 filed December 19, 2025; hereafter “Li”), To et al. (Antioxid. Redox Signal. 32:929-942, 2020; cited on Form PTO-892 filed December 19, 2025; hereafter “To”), and Hazra et al. (US 2020/0102358 A1; cited on Form PTO-892 filed December 19, 2025; hereafter “Hazra”)
the rejection of claims 1, 2, 4-9, 11-13, and 16-18 under 35 U.S.C. 103 as being unpatentable over Wilson in view of Li, To, and Hazra as applied to claim 19 above, and further in view of Tavares et al. (Inflamm. Res. 66:283-302, 2017; cited on Form PTO-892 filed December 19, 2025; hereafter “Tavares”),
the rejection of claims 14 and 15 under 35 U.S.C. 103 as being unpatentable over Wilson in view of Li, To, Hazra, and Tavares as applied to claims 1, 2, 4-9, 11-13, and 16-18 above, and further in view of Prasun, P. (DNA Cell Biol. 40:713-719, 2021; cited on Form PTO-892 filed December 19, 2025; hereafter “Prasun”),
the rejection of claim 19 under 35 U.S.C. 103 as being unpatentable over Wilson in view of Sarker et al. (Prog. Biophys. Mol. Biol. 164:72-80, March 20, 2021; cited on Form PTO-892 filed December 19, 2025; hereafter “Sarker"), Li, To, and Hazra,
the rejection of claims 1, 2, 4-9, 11-13, and 16-18 under 35 U.S.C. 103 as being unpatentable over Wilson in view of Sarker, Li, To, and Hazra as applied to claim 19 above, and further in view of Tavares, and
the rejection of claims 14 and 15 under 35 U.S.C. 103 as being unpatentable over Wilson in view of Sarker, Li, To, Hazra, and Tavares as applied to claims 1, 2, 4-9, 11-13, and 16-18 above, and further in view of Prasun
are maintained for the reasons of record.
RESPONSE TO REMARKS: In summary, applicant argues the Hazra Declaration establishes that inhalation therapy with NEIL2 to a subject infected with SARS-CoV-2 has the unexpected effect of RNA-level antiviral activity due to NEIL2 binding to SARS-CoV-2 genomic RNA, and according to applicant, this unexpected result is commensurate in scope with the claims and is sufficient to rebut a prima facie case of obviousness.
Applicant’s arguments and Hazra Declaration are not found persuasive. According to MPEP 716.02(d), unexpected results must be reasonably commensurate in scope with the claimed invention. “Commensurate in scope” means that the evidence provides a reasonable basis for concluding that the untested embodiments encompassed by the claims would behave in the same manner as the tested embodiments. See In re Lindner, 457 F.2d 506, 508 (CCPA 1972). Although not expressly stated by applicant, applicant’s results appear to be based on inhalation therapy with a specific NEIL2 fusion protein (NEIL2 protein of SEQ ID NO: 1 and a lung cell targeting segment of SEQ ID NO: 9) to a subject infected with a specific virus (SARS-CoV-2). While nonobviousness of a broader claimed range can be supported by evidence based on unexpected results from testing a narrower range (MPEP 716.02(d).I), there is no evidence of record that the untested embodiments encompassed by the claims (e.g., administering NEIL2 by any route including oral or intravenous administration, using variants and mutants of NEIL2 of SEQ ID NO: 1, e.g., a variant of NEIL2 that does not bind to SARS-CoV-2 genomic RNA or a NEIL2 protein without a lung targeting segment, and subjects infected with any virus) would behave in the same manner as the tested embodiment(s). In this case, applicant’s results are not commensurate in scope with the claimed invention and consequently fail to rebut a prima facie case of obviousness.
Applicant further argues the cited references fail to motivate one of ordinary skill in the art to apply NEIL2 to a viral infection because none of the cited references teaches NEIL2 for the viruses. Applicant argues that although Hazra and Wilson taught treating bacterial inflammation or general inflammation with NEIL2, there would have been no motivation to combine the references to treat viral infection because viral pathology involves unique mechanisms such as cytokine storms that are distinct from treating bacterial inflammation or general inflammation with NEIL2.
Applicant’s arguments are not found persuasive. There is no dispute that no single reference among the cited prior art teaches administering NEIL2 to treat a viral infection, however, the rejections are based on a combination of references. As stated in the prior Office action, the prior art taught or suggested treating a disease by administering NEIL2 to reduce production of reactive oxygen species (ROS), oxidative stress, and oxidative-stress induced damage to mitochondrial DNA (e.g., Wilson and Hazra), the prior art taught or suggested influenza A and SARS-CoV-2 viral infections promote ROS, oxidative stress, and oxidative damage to mitochondrial DNA (e.g., Sarker, Li, To, Tavares, and Prasun), and the prior art taught or suggested treatment of influenza A and SARS-CoV-2 viral infections by inhibiting ROS, oxidative stress, and damage to mitochondrial DNA (e.g., Sarker, To, Tavares, and Prasun). Contrary to applicant’s position, in view of the combined teachings of the cited prior art, one of ordinary skill would have been motivated to administer NEIL2 to treat a viral infection.
For these reasons, it is the examiner’s position that the claimed invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date.
Claim Rejections - Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP §§ 706.02(l)(1) - 706.02(l)(3) for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
The rejection of claim 19 on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 of U.S. Patent No. 11,851,464 B2 in view of Wilson, Sarker, Li, and To, and
the rejection of claims 1, 2, 4-9, 11-13, and 16-18 on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 of U.S. Patent No. 11,851,464 B2 in view of Wilson, Sarker, Li, and To as applied to claim 19 above, and further in view of Tavares,
the rejection of claims 14 and 15 on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 of U.S. Patent No. 11,851,464 B2 in view of Wilson, Sarker, Li, To, and Tavares as applied to claims 1, 2, 4-9, 11-13, and 16-19 above, and further in view of Prasun,
the rejection of claim 19 on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 of U.S. Patent No. 11,851,464 B2 in view of Wilson, Li, and To,
the rejection of claims 1, 2, 4-9, 11-13, and 16-18 on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 of U.S. Patent No. 11,851,464 B2 in view of Wilson, Li, and To as applied to claim 19 above, and further in view of Tavares, and
the rejection of claims 14 and 15 on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 of U.S. Patent No. 11,851,464 B2 in view of Wilson, Li, To, and Tavares as applied to claims 1, 2, 4-9, 11-13, and 16-19 above, and further in view of Prasun
are maintained for the reasons of record.
RESPONSE TO REMARKS: In summary, applicant argues the claims of the patent are directed to treating bacterial lung infections, which are patentably distinct from the claims of this application because bacterial and viral infections involve different pathological mechanisms, immune responses, and treatment considerations, rendering the extension from bacterial to viral contexts non-obvious.
Applicant’s arguments are not found persuasive. As stated in the prior Office action, the prior art taught or suggested treating a disease by administering NEIL2 to reduce production of reactive oxygen species (ROS), oxidative stress, and oxidative-stress induced damage to mitochondrial DNA (e.g., Wilson and Hazra), the prior art taught or suggested influenza A and SARS-CoV-2 viral infections promote ROS, oxidative stress, and oxidative damage to mitochondrial DNA (e.g., Sarker, Li, To, Tavares, and Prasun), and the prior art taught or suggested treatment of influenza A and SARS-CoV-2 viral infections by inhibiting ROS, oxidative stress, and damage to mitochondrial DNA (e.g., Sarker, To, Tavares, and Prasun). Contrary to applicant’s position, in view of the claims of the patent in combination with the cited teachings of the prior art, one of ordinary skill would have been motivated and would have reasonably expected success to administer NEIL2 to treat a viral infection.
Applicant further argues the Hazra Declaration provides evidence of unexpected results, which is objective indicia of non-obviousness.
Applicant’s arguments and Hazra Declaration are not found persuasive. For reasons stated above, applicant’s results are not commensurate in scope with the claimed invention and consequently fail to rebut a prima facie case of obviousness.
Conclusion
Status of the claims:
Claims 1-19 and 40 are pending.
Claims 3 and 10 are withdrawn from consideration.
Claims 1, 2, 4-9, 11-19, and 40 are rejected.
No claim is in condition for allowance.
THIS ACTION IS MADE FINAL. 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 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
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