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 1-5 are pending in the application. Claims 1 and 3-5 are rejected. Claim 2 is withdrawn from further consideration.
Election/Restrictions
Applicant’s election without traverse of the species of disulfiram in the reply filed on November 9th, 2023 is acknowledged.
As per MPEP 803.02, the examiner will determine whether the entire scope of the claims is patentable. Applicants' elected species is not allowable. MPEP 803.02 states:
Following election, the Markush claim will be examined fully with respect to the elected species and further to the extent necessary to determine patentability. […]
If the Markush claim is not allowable, the provisional election will be given effect and examination will be limited to the Markush claim and claims to the elected species, with claims drawn to species patentably distinct from the elected species held withdrawn from further consideration. […]
If on examination the elected species is found to be anticipated or rendered obvious by prior art, the Markush claim and claims to the elected species will be rejected, and claims to the nonelected species will be held withdrawn from further consideration.
As the elected species has been found not allowable, the Markush-type claims have been rejected and claims to the nonelected invention held withdrawn from further consideration. Claims 1 and 3-5 embraced the elected species and are therefore under examination. Claims 1 and 3-5 have been examined to the extent that they are readable on the elected embodiment. Since the elected species is not allowable, subject matter not embraced by the elected embodiment is therefore withdrawn from further consideration.
Additional issues (under 35 USC 102 where the pyroptosis inhibitor is dexamethasone and under 112(d)) were discovered incidental to the search of the elected species and are presented below in the interest of compact prosecution.
Claim 2 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on December 22nd, 2025.
Priority
Since each claim under examination is supported by Provisional Application No. 63/378,112, the claims under examination have an effective filing date of October 3rd, 2022.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 3 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 3 recites the pyroptosis inhibitor is disulfiram, which does not fall within the scope of formula (II) that contains a carbon bound to R3 and R4 instead of nitrogen. Even if claim 2 were amended to contain a structure embracing disulfiram, the instant specification defines the term “disulfiram” on page 8, lines 22-27 as embracing metabolites that would not fall within formula (II) if amended to contain two nitrogens. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 102
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.
Claim(s) 1, 4 and 5 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Tan et al. Experimental Eye Research, 2022, 214, 108858, which was available online November 23rd, 2021 and as evidenced by Thermo Scientific, MSDS for sodium hydroxide, 2021.
Tan et al. teach the introduction of sodium hydroxide caused burns on the cornea of mice on page 2 (Section 2.3). The authors further note that dexamethasone phosphate (Dex) was administered to mice having corneal burns as follows (Section 2.3): “In addition, alkali burn models were established as day 0, different concentrations of Dex eyedrops (or PBS as the excipient in the model group) were treated topically, and treatment was repeated 4~6 times per day for day 3 or day 7.” The prior art further teaches in the abstract: “In addition, Dex can inhibit pyroptosis through this pathway.” Accordingly, the prior art teaches that dexamethasone phosphate is a pyroptosis inhibitor and that it was administered to the cornea of a subject in a pharmaceutical carrier for treating a chemical burn induced by alkali. This method is 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 anticipate claim 5 in treating sodium hydroxide induced burns.
Claim(s) 1, 4 and 5 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Bian et al. Int. J. Mol. Sci. 2017, 18, 562 and as evidenced by Tan et al. Experimental Eye Research, 2022, 214, 108858 and as further evidenced by Thermo Scientific, MSDS for sodium hydroxide, 2021.
Bian et al. teach the following steps on page 11 (Section 4.7):
Mice subjected to corneal alkali burn were topically treated either with 2 µL of sodium butyrate (0.5 Mm, Sigma–Aldrich), 2 µL of hydroxybutyric acid (80 mM, Sigma–Aldrich), sodium phosphate dexamethasone (0.1%, Spectrum Laboratory, Gardena, CA, USA), or vehicle (balanced salt solution, Alcon, Fort Worth, TX, USA) QID for 2 or 5 days.
The prior art further teaches that alkali burns were generated using sodium hydroxide on page 9 (Section 4.2). The evidentiary reference by Tan et al. teaches in the abstract: “In addition, Dex can inhibit pyroptosis through this pathway.” Accordingly, Bian et al. teaches administration of dexamethasone, which inhibits pyroptosis, to the cornea of a subject in a pharmaceutical carrier for treating a chemical burn induced by alkali. This method is 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 anticipate claim 5 in treating sodium hydroxide induced burns.
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, 3, 4 and 5 is/are rejected under 35 U.S.C. 103 as being unpatentable over WO 2021/135654 A1 by Hu et al. (where a machine translation is appended to the reference and will be referred to herein) 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, 3, 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
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/MATTHEW P COUGHLIN/Primary Examiner, Art Unit 1626