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 .
Status of the Application
Claims 1, 7, 10, 13 and 16-17 are pending as of the response filed 11/10/2025. Claims 2-6, 8-9, 11-12 and 14-15 are cancelled. Applicant’s election of a species of the active component being administered, as disulfiram is maintained. Claims 1, 7, 10, 13 and 16-17 are examined herein.
The 35 U.S.C. 102 rejection over Poitou is withdrawn in consideration of the claim amendments.
Applicant’s arguments have been fully considered but were not found to be persuasive. Specifically, Applicant’s conclude on page 6 of their response dated 11/10/2025 that “A chronic pain at the spinal level includes not only neuropathic pain but also pains of other mechanisms such as nociceptive pain, as evidenced by the following publications”. Therefore, the Marchand reference that teaches that an innovative pharmacological approach for treatment of chronic pain at the spinal level may include Antabuse (i.e., disulfiram) pretreatment, provides motivation to treat neuropathic pain using disulfiram.
Thus, the statutory basis of the 35 U.S.C. 102 rejection of record over Marchand is changed to a 103.
The 35 U.S.C. 103 rejection of record over Rahman in view of Marchand is maintained.
Since the change in statutory basis of the rejection over Marchand constitutes a new ground of rejection, this Office action is non-final.
Applicant’s arguments are addressed in detail below.
Claim Rejections - 35 USC § 103 - New
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 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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 7, 13 and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Marchand et al. (Disulfiram Administration Affects Substance P-like Immunoreactive and Monoaminergic Neural Systems in Rodent Brain*, 05 January 1990, hereinafter Marchand).
Regarding instant claims 1 and 13, Marchand teaches subcutaneously injecting mice with 100 mg/kg disulfiram (Pg. 265, first column, first full paragraph). Marchand teaches levels of substance P-like neurochemical parameter (SP-LI) were significantly reduced in the spinal cords of disulfiram-treated animals as compared to controls (Pg. 266, second column, last paragraph; FIG. 1A) (substance P is a pain neurotransmitter and a reduction in substance P is associated with a decrease in pain signaling or analgesia). Marchand teaches a gradual increase in tailflick latency in disulfiram-treated animals versus controls with statistical significance (p<0.05) (Pg. 269, second column, last paragraph) (an increase in tailflick latency as monitored by thermal nociceptive response is interpreted as analgesia or a reduction in pain sensitivity – thus, the amount of disulfiram administered is considered an effective amount since it brings about the desired result of analgesia). Marchand teaches an innovative pharmacological approach to treat chronic pain at the spinal level (i.e., pain that includes neuropathic pain) may include Antabuse (i.e., disulfiram) pretreatment (Pg. 272, second column, continued paragraph). The teachings of Marchand provide motivation to a person of ordinary skill in the art to consider disulfiram as a candidate for investigation in neuropathic pain. Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, in view of the teachings of Marchand to have utilized disulfiram in a method of treating neuropathic pain, with a reasonable expectation of success.
Regarding instant claims 7 and 16, Marchand teaches 100 mg/kg disulfiram in 0.5% Tween 80/saline (Pg. 265, first column, first full paragraph). Therefore, Marchand teaches a pharmaceutical composition of disulfiram consisting of one or more pharmaceutically acceptable additives as in instant claims 7 and 16.
Claim Rejections - 35 USC § 103 - Maintained
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 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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 7, 13 and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Rahman et al. (Disulfiram Causes Sustained Behavioral and Biochemical Effects in Rats, 1997, hereinafter Rahman) in view of Marchand et al. (Disulfiram Administration Affects Substance P-like Immunoreactive and Monoaminergic Neural Systems in Rodent Brain*, 05 January 1990, hereinafter Marchand).
Regarding instant claim 1 and 13, Rahman teaches both high and low doses of disulfiram administered to rats caused significant increases in hot plate latency (Pg. 411, second column, first full paragraph). Rahman teaches hot plate tests were used as indices for nociception (Pg. 410, first column, second full paragraph). Further, higher hot-plate latency period indicates greater analgesia.
Rahman do not teach wherein the pain to be relieved is neuropathic pain.
Marchand teaches subcutaneously injecting mice with 100 mg/kg disulfiram (Pg. 265, first column, first full paragraph) resulted in significant reduction in levels of substance P-like neurochemical parameter (SP-LI) in the spinal cords of disulfiram-treated animals as compared to controls (Pg. 266, second column, last paragraph; FIG. 1A) (substance P is a pain neurotransmitter and a reduction in substance P is associated with a decrease in pain signaling or analgesia). Marchand teaches a gradual increase in tailflick latency in disulfiram-treated animals versus controls with statistical significance (p<0.05) (Pg. 269, second column, last paragraph) (an increase in tailflick latency as monitored by thermal nociceptive response is interpreted as analgesia or a reduction in pain sensitivity). Marchand teaches an innovative pharmacological approach to treat chronic pain at the spinal level (i.e., pain that includes neuropathic pain) may include Antabuse (i.e., disulfiram) pretreatment (Pg. 272, second column, continued paragraph).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, in view of the teachings of Rahman and Marchand to have utilized disulfiram as taught by Rahman in a method of treating neuropathic pain, with a reasonable expectation of success. Rahman teaches both high and low doses of disulfiram administered to rats caused significant increases in hot plate latency. Rahman teaches hot plate tests were used as indices for nociception. The teachings of Rahman indicates greater analgesia. Marchand teaches subcutaneously injecting mice with 100 mg/kg disulfiram resulted in significant reduction in levels of substance P-like neurochemical parameter (SP-LI) in the spinal cords of disulfiram-treated animals as compared to controls, indicating analgesia at the spinal level (i.e., pain that includes neuropathic pain). Therefore, one of ordinary skill in the art would have been motivated to use disulfiram in a method of treating neuropathic pain. The teachings of Rahman in view of Marchand render the limitations of instant claims 1 and 13, prima facie obvious.
Regarding instant claims 7 and 16, the teachings of Rahman in view of Marchand render the method for analgesia as in instant claim 1, prima facie obvious. Rahman teaches disulfiram suspended in 0.9% NaCl containing 0.5% Tween 80 (Pg. 410, second column, first full paragraph). Therefore, the teachings of Rahman render the limitations of instant claim 7 drawn to a method of administering to said subject a pharmaceutical composition of disulfiram consisting of one or more pharmaceutically acceptable additives, prima facie obvious.
Response to Arguments
Applicants argue on pages 6-10 of the response dated 11/10/2025, that “A chronic pain at the spinal level includes not only neuropathic pain but also pains of other mechanisms such as nociceptive pain, as evidenced by the following publications” – i.e., Park et al. and Spahr et al.. Applicants argue “Marchand's publication is silent on the specific topic of neuropathic pain, nerve injury, or nerve damage”. Applicants argue Marchand only reports a "very weak" effect on nociceptive pain (the standard "tailflick" test), with a significant difference in latency observed only after a prolonged (16-day) and high-dose treatment regimen. Applicants argue “While disulfiram treatment reduced substance P-like immunoreactivity (SP-LI) levels in the spinal cord by about 30%, a substantial 70% of the level remained”. Applicants assert that Marchand does not demonstrate this 30% reduction is sufficient to produce an analgesic effect for neuropathic pain. Applicants conclude that “a skilled person would not be motivated to use disulfiram to treat neuropathic pain”.
Applicant's arguments have been fully considered but they are not persuasive.
While Marchand’s results may be geared towards the study of nociceptive pain responses to disulfiram treatment, nevertheless, Marchand teaches disulfiram may be used as a pretreatment for chronic pain at the spinal level. Applicants acknowledge (in page 6 of their response dated 11/10/2025) that chronic pain at the spinal level includes not only neuropathic pain but also pains of other mechanisms such as nociceptive pain.
According to MPEP 2123 (I), A reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill in the art, including nonpreferred embodiments. Merck & Co. v. Biocraft Labs., Inc. 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989). In the instant case, the study of Marchand focuses on the functional outcome - increased pain threshold - as the key indicator of potential therapeutic value, despite a large amount of SP-LI remaining in the spinal cord. Therefore, even though approximately 70% of total SP-LI level was maintained, the observed increase in pain threshold suggests that disulfiram affects relevant pain-signaling pathways and is a potential candidate for further investigation into neuropathic pain treatment.
According to MPEP 2143.01, “Obviousness can be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so. In re Kahn, 441 F.3d 977, 986, 78 USPQ2d 1329, 1335 (Fed. Cir. 2006)”. Contrary to Applicant’s contention, Marchand provides motivation to test disulfiram in the treatment of neuropathic pain.
As such, as detailed in the 103 rejections above, the teachings of Marchand render obvious the instant method for analgesia, comprising administering an effective amount of disulfiram to a subject, wherein the pain to be relieved is a neuropathic pain.
Additionally, the examiner notes that disulfiram is known to cause peripheral neuropathy (Rahman, Pg. 409, first column, last paragraph) and its effects may be dose and duration dependent (Pg. 410, second column, fourth full paragraph). The claims, as recited, are drawn broadly to administering an effective amount of disulfiram, with no specific dosages claimed. It is unclear if certain dosages of disulfiram may be critical to relieving neuropathic pain, as instantly claimed.
Applicants are encouraged to present a clear and convincing evidence of nonobviousness or unexpected results in light of the prior art, to overcome the rejections of record.
Allowable Subject Matter
Claims 10 and 17 are objected to as being dependent upon a rejected base claim, but would be allowable (with respect to the elected species of disulfiram) if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
The following is a statement of reasons for the indication of allowable subject matter:
While, Marchand and Rahman are the closest prior art, they do not teach wherein the analgesic effect with respect to treating neuropathic pain is solely caused by disulfiram, not in combination with another analgesic drug.
Conclusion
Claims 1, 7, 13 and 16 are rejected.
Claims 10 and 17 are objected to.
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PADMAJA S RAO whose telephone number is (571) 272-9918. The examiner can normally be reached 9:00-5:30 pm EDT.
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/P.S.R./Examiner, Art Unit 1627
/SARAH PIHONAK/Primary Examiner, Art Unit 1627