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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 6/12/2026 has been entered.
Applicant’s cancellation of claims 1-6 and the addition of new claims 7 and 8, in the paper of 6/12/2026, is acknowledged. Applicants' arguments filed on 6/12/2026, have been fully considered and are deemed to be persuasive to overcome some of the rejections previously applied. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. Claims 7 and 8 are at issue and are present for examination.
Applicants previous claim 1 and newly added claim 7 are presented herein as a reference:
1. (Previous) A method for improving mitochondrial functions in cells of a subject having a condition associated with decreased mitochondrial membrane potential, comprising:
(a) administering to the subject in need thereof a composition comprising a reactive persulfide in an amount effective to increase mitochondrial membrane potential without inhibiting mitochondrial respiratory complex IV: and
(b) increasing the mitochondrial membrane potential in the subject's cells by the administered reactive persulfide, thereby improving mitochondrial function.
7. (New) A method for improving mitochondrial dysfunction in a subject having mitochondrial dysfunction associated with mitochondrial respiratory chain complex I deficiency, comprising:
administering to the subject a composition comprising glutathione trisulfide (GSSSG) in an amount sufficient to improve mitochondrial energy metabolism to a level comparable to a 3 to 10 mM NaHS-equivalent experimental reference level described, under conditions that do not inhibit mitochondrial respiratory complex IV,
wherein the improvement in the mitochondrial dysfunction is mediated via an electron transfer pathway involving sulfide oxidoreductase (SQR).
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 7 and 8 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 7 (claim 8 dependent from) is indefinite in that it is drawn to a method for improving mitochondrial dysfunction in a subject having mitochondrial dysfunction associated with mitochondrial respiratory chain complex I deficiency. It is unclear what “a mitochondrial dysfunction associated with mitochondrial respiratory chain complex I deficiency” is. Applicants specification does not define or discuss what a mitochondrial dysfunction associated with mitochondrial respiratory chain complex I deficiency. Applicants discussion of and statement that “the limitation directed to mitochondrial dysfunction associated with complex I deficiency can be reasonably explained based at least on paragraphs [0033] and [0042]” in applicants response (page 5/9, lines 15-30 of response of 6/12/2026) is not found persuasive. Further it is noted that previously applicants claim was drawn to a method for improving mitochondrial functions in cells of a subject having a condition associated with decreased mitochondrial membrane potential.
Thus the claimed method is indefinite in that it is unclear who the “subject” for which the administering is to.
Claim 7 (claim 8 dependent from) further indefinite in that the claimed method comprises administering to the subject a composition comprising glutathione trisulfide (GSSSG) in “an amount sufficient to improve mitochondrial energy metabolism to a level comparable to a 3 to 10 mM NaHS-equivalent experimental reference level described”. The above amount is indefinite. What amount is sufficient to improve mitochondrial energy metabolism to a level comparable to a 3 to 10 mM NaHS-equivalent experimental reference level described. What is a level comparable to a 3 to 10 mM NaHS-equivalent experimental reference level described? Applicants specification does not address the above indefiniteness. Applicants discuss somewhat in applicants response page 6/9 line 25 thru page 7/9 line 14, however such is not found persuasive in overcoming the rejection based upon indefiniteness of “an amount sufficient to improve mitochondrial energy metabolism to a level comparable to a 3 to 10 mM NaHS-equivalent experimental reference level described”.
In the interest of advancing prosecution, “an amount sufficient to improve mitochondrial energy metabolism to a level comparable to a 3 to 10 mM NaHS-equivalent experimental reference level described” is interpreted as any therapeutic or pharmalogical amount.
Claim 7 (claim 8 dependent from) is further indefinite in that the recitation “under conditions that do not inhibit mitochondrial respiratory complex IV” in that it is not known what such conditions that do not inhibit mitochondrial respiratory complex IV are. Applicants specification does not discuss or shed light on such conditions. Applicants comments in applicants response at page 7/9 lines 14-25 are acknowledged, however, not found persuasive in defining said conditions.
Claim 7 (claim 8 dependent from) recites the limitation "the improvement in mitochondrial dysfunction" in the claim. There is insufficient antecedent basis for this limitation in the claim. In the interest of advancing prosecution "the improvement in mitochondrial dysfunction" is interpreted as "the improving mitochondrial dysfunction".
Claim 7 (claim 8 dependent from) recites the limitation "the improvement in mitochondrial dysfunction" in the claim. There is insufficient antecedent basis for this limitation in the claim. In the interest of advancing prosecution "the improvement in mitochondrial dysfunction" is interpreted as "the improving mitochondrial dysfunction".
Claim 8 recites the limitation "the improvement in mitochondrial energy metabolism" in the claim 7. There is insufficient antecedent basis for this limitation in claim 7. In the interest of advancing prosecution " the improvement in mitochondrial energy metabolism " is interpreted as "the improving mitochondrial energy metabolism ".
Appropriate amendment and/or comment is requested.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claim(s) 7-8 are rejected 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. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
Newly added claims 7 and 8 drawn to a method for improving mitochondrial dysfunction in a subject having mitochondrial dysfunction associated with mitochondrial respiratory chain complex I deficiency, comprising: administering to the subject a composition comprising glutathione trisulfide (GSSSG) in an amount sufficient to improve mitochondrial energy metabolism to a level comparable to a 3 to 10 mM NaHS-equivalent experimental reference level described, under conditions that do not inhibit mitochondrial respiratory complex IV, wherein the improvement in the mitochondrial dysfunction is mediated via an electron transfer pathway involving sulfide oxidoreductase (SQR) are not supported by applicants specification at the time of filing and are thus considered new matter (see also above rejection under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph).
Applicants claimed method for improving mitochondrial dysfunction in a subject having mitochondrial dysfunction associated with mitochondrial respiratory chain complex I deficiency are not supported by applicants specification at the time of filing. Further applicants claimed method of administering to the subject a composition comprising glutathione trisulfide (GSSSG) in an amount sufficient to improve mitochondrial energy metabolism to a level comparable to a 3 to 10 mM NaHS-equivalent experimental reference level described, under conditions that do not inhibit mitochondrial respiratory complex IV are not supported by applicants specification at the time of filing.
Claim(s) 7-8 are rejected 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. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim(s) 7-8 are directed to all possible methods for improving mitochondrial dysfunction in a subject having mitochondrial dysfunction associated with mitochondrial respiratory chain complex I deficiency, comprising: administering to the subject a composition comprising glutathione trisulfide (GSSSG) in an amount sufficient to improve mitochondrial energy metabolism to a level comparable to a 3 to 10 mM NaHS-equivalent experimental reference level described, under conditions that do not inhibit mitochondrial respiratory complex IV, wherein the improvement in the mitochondrial dysfunction is mediated via an electron transfer pathway involving sulfide oxidoreductase (SQR) (see also above rejection under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph). The specification does not provide a single method improving mitochondrial dysfunction in a subject having mitochondrial dysfunction associated with mitochondrial respiratory chain complex I deficiency, comprising: administering to the subject a composition comprising glutathione trisulfide (GSSSG) in an amount sufficient to improve mitochondrial energy metabolism to a level comparable to a 3 to 10 mM NaHS-equivalent experimental reference level described, under conditions that do not inhibit mitochondrial respiratory complex IV, wherein the improvement in the mitochondrial dysfunction is mediated via an electron transfer pathway involving sulfide oxidoreductase (SQR), encompassed by these claims. There is no disclosure of the amount sufficient to improve mitochondrial energy metabolism to a level comparable to a 3 to 10 mM NaHS-equivalent experimental reference level described in the claimed method. General Hospital Corporation (WO 2021/231476) disclose methods for the treatment, or reduction of risk, of a disorder associated with neurodegeneration in a subject, the method comprising administering a therapeutically or prophylactically effective amount of a composition prepared using crystals of Glutathione Trisulfide (GSSSG) to a subject in need thereof wherein the amount is 282 µM. While applicants specification describes methods of administration of NaHS to yeast cell cultures at 3 to 10 µM applicants specification fails to disclose those amount sufficient to improve mitochondrial energy metabolism to a level comparable to a 3 to 10 mM NaHS-equivalent experimental reference level described, for which no predictability is apparent.
Given the lack of disclosure of methods encompassed by the claims, Applicants have failed to sufficiently describe the claimed invention, in such full, clear, concise, and exact terms that a skilled artisan would recognize Applicants were in possession of the claimed invention.
Applicant is referred to the revised guidelines concerning compliance with the written description requirement of U.S.C. 112, first paragraph, published in the Official Gazette and also available at www.uspto.gov.
Applicants Response
Applicants comments regarding the previous rejection of now canceled claims 1-6 are acknowledged, however, not found persuasive in overcoming the rejection of current claims 7 and 8 for the reasons stated above.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
The rejection of claim(s) 1 is/are rejected under 35 U.S.C. 102 (a)(1) and (a)(2) as being anticipated by Goubern et al. (FASEB J., Vol 21, pp 1699-1706, June 2007) as evidenced by Landry et al. (Cell Chemical Biology, 26, pp 1515-1525, Nov 2019) is withdrawn based upon applicants amendment of the claims and applicants arguments presented in the paper of 11/17/2025. Specifically Goubern et al. does not teach administering to the subject in need thereof a composition comprising a reactive persulfide. Goubern et al. disclose administering a sulfide.
The rejection of claim(s) 1 and 2 under 35 U.S.C. 102) (a)(2) as being anticipated by General Hospital Corporation (WO 2021/231476) is withdrawn based upon applicants cancellation of claims 1 and 2, in the paper of 6/12/2026.
Claim(s) 7 and 8 is/are rejected under 35 U.S.C. 102) (a)(2) as being anticipated by General Hospital Corporation (WO 2021/231476).
General Hospital Corporation (WO 2021/231476) teach a method for the treatment, or reduction of risk, of a disorder associated with neurodegeneration in a subject, the method comprising administering a therapeutically or prophylactically effective amount of a composition prepared using crystals of Glutathione Trisulfide (GSSSG) to a subject in need thereof. While General Hospital Corporation may not teach that as a result of the above administering of GSSSG, they are improving mitochondrial dysfunction, or that the improving mitochondrial dysfunction is mediated via an electron transfer pathway involving sulfide oxidoreductase (SQR), this is considered an inherent properties of the method of the administration of GSSSG taught by General Hospital Corporation. It is noted that claim 8 is included in this rejection because claim 8 doses not include an active step of the method but rather claim 8 is interpreted as further limiting “the amount sufficient to improve mitochondrial energy metabolism…” (see above rejection under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph).
Thus claim(s) 7 and 8 is/are rejected under 35 U.S.C. 102) (a)(2) as being anticipated by General Hospital Corporation (WO 2021/231476).
Related Art not used in a Rejection
Babidge et al., Molecular and Cellular Biochemistry, Vol 181, pp 117-124, 1998.
Remarks
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RICHARD G HUTSON whose telephone number is (571)272-0930. The examiner can normally be reached 6-3 EST Mon-Fri.
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rgh
8/6/2026
/RICHARD G HUTSON/Primary Examiner, Art Unit 1652
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