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 .
DETAILED ACTION
Claims 1, 4 and 5 are pending in the application. Claims 1, 4 and 5 are rejected.
Information Disclosure Statement
The Examiner has considered the Information Disclosure Statement(s) filed on February 4th, 2026.
Response to Amendment / Argument
Rejections made in the previous Office Action that do not appear below have been overcome by Applicant's amendments to the claims. Therefore, arguments pertaining to these objections and rejections will not be addressed.
Beginning on page 1 of the response filed June 29th, 2026, Applicant traverses the rejection of claims under 35 USC 103. Applicant summarizes the prior art references in the paragraph bridging pages 1 and 2 of the response and then refers to a lack of reasonable expectation of success and unexpected results. Regarding reasonable expectation of success, Applicant refers to Hu’s disclosure of oral administration. One cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). In this situation, the secondary reference demonstrates that compounds inhibiting NLRP3 can be administered to the cornea.
Regarding unexpected results, Applicant refers to data found in the specification regarding disulfiram. As noted in MPEP 716.02(d): “Whether the unexpected results are the result of unexpectedly improved results or a property not taught by the prior art, the "objective evidence of nonobviousness must be commensurate in scope with the claims which the evidence is offered to support." In other words, the showing of unexpected results must be reviewed to see if the results occur over the entire claimed range. In re Clemens, 622 F.2d 1029, 1036, 206 USPQ 289, 296 (CCPA 1980)”. In this situation, the instant claims place no limitation on dosage or formulation being applied and the narrow demonstrations do not establish when these alleged unexpected results would be observed. Regardless, MPEP 716.02(e) states: “An affidavit or declaration under 37 CFR 1.132 must compare the claimed subject matter with the closest prior art to be effective to rebut a prima facie case of obviousness. In re Burckel, 592 F.2d 1175, 201 USPQ 67 (CCPA 1979).” In this situation, the prior art demonstrates administration of NLRP3 inhibitors can be used to limit cornea damage after alkali burns and there has been no comparison relative to the prior art’s demonstrated utility.
For these reasons, the rejection under 35 USC 103 is maintained over claims 1, 4 and 5.
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.
Claim(s) 1, 4 and 5 is/are rejected under 35 U.S.C. 103 as being unpatentable over WO 2021/135654 A1 by Hu et al. in view of Bian et al. Int. J. Mol. Sci. 2017, 18, 562 and as evidenced by Thermo Scientific, MSDS for sodium hydroxide, 2021.
Determining the scope and contents of the prior art. (See MPEP § 2141.01)
Hu et al. teach methods of using disulfiram to prevent or treat NLRP3 inflammation-related diseases in paragraph [0004]:
Based on this, it is an object of the present invention to provide an application of disulfiram in the preparation of a drug for preventing and treating NLRP3 inflammation-related diseases.
Hu et al. generally teach the following properties of dilsufiram in paragraph [0010]:
The inventors of the present invention surprisingly found that disulfiram effectively inhibits the activation of NLRP3 inflammation, inhibits the maturation and secretion of inflammatory activation signal molecules Caspase -1 P20 and inflammatory cytokines IL -1 β, has a good control effect on NLRP3 inflammation-related diseases, especially for peritonitis and gout arthritis, and has a significant control effect.
Ascertainment of the differences between the prior art and the claims. (See MPEP § 2141.02)
Hu et al. do not teach treating a chemical burn as an embodiment of an NLRP3 inflammation-related disease. Additional limitations and dependent claims are addressed below.
Finding of prima facie obviousness --- rationale and motivation (See MPEP § 2141.02)
Bian et al. teach treating alkali burns in mice and the following results (abstract):
[…] We found elevation of NLRP3 and IL-1β messenger RNA (mRNA) transcripts, as well as levels of inflammasome component proteins in the alkali-injured corneas compared to naïve corneas. Treatment with NLRP3 inhibitors using NaB and HBA preserved corneal clarity and decreased NLRP3, caspase-1, and IL-1β mRNA transcripts, as well as NLRP3 protein expression on post-injury compared to BSS-treated corneas. These findings identified a novel innate immune signaling pathway activated by AB. Blocking the NLRP3 pathway in AB mouse model decreases inflammation, resulting in greater corneal clarity. These results provide a mechanistic basis for optimizing therapeutic intervention in alkali injured eyes.
The authors provide similar conclusions on page 2 as follows:
Here, we show that a novel innate immune signaling pathway (NLRP3–ASC–caspase-1–IL-1β) is activated in corneal epithelial cells by alkali burn. Blocking the NLRP3 pathway reduced inflammation, leading to improved wound healing and corneal clarity.
Regarding the burn being treated, Bian et al. teach on page 9 (Section 4.2) that NaOH was used to create an alkali burn. The authors further treatment methods that involve administration of active compound in a vehicle on page 11 (Section 4.7). At least since Bian et al. teach inhibition of NLRP3 being used in the treatment of alkali burns, a person having ordinary skill in the art in seeking to expand the utility of Hu et al. would have reasonably expected an alkali burn of a cornea to fall within the scope of an NLRP3 inflammasome-related disease. In the interest of determining which known NLRP3 inflammasome inhibitors would provide optimum results, a person having ordinary skill in the art would have at least been motivated to test compounds known to possess analogous properties as those tested by Bian et al., i.e. including disulfiram as instantly claimed. A person having ordinary skill in the art would have at least been motivated to repeat the assays of Bian et al. using disulfiram, which would have involved treating an NaOH induced chemical burn of a cornea and administering disulfiram in a pharmaceutical carrier. This method would be embraced by instant claims 1, 4 and 5.
Regarding instant claim 5, the evidentiary reference (MSDS for sodium hydroxide) by Thermo Scientific notes in Section 4 that “blistering may occur”. Accordingly, since a vesicant is considered an agent that causes blistering, the prior art is deemed to render obvious claim 5 in treating sodium hydroxide induced burns.
Conclusion
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.
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/MATTHEW P COUGHLIN/Primary Examiner, Art Unit 1626
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