DETAILED ACTION
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. 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 for the cited rejections 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.
3. Response to Election/Restriction filed on 7/21/2026 is acknowledged.
4. Claim filed on 12/14/2023 is acknowledged.
5. Claims 1, 2, 5-8 and 11-14 have been cancelled.
6. New claims 17 and 18 have been added.
7. Claims 3, 4, 9, 10 and 15-18 are pending in this application.
8. Claims 9, 10 and 15-18 are withdrawn from consideration pursuant to 37 CFR 1.142(b), as being drawn to non-elected inventions, there being no allowable generic or linking claim.
9. Claims 3 and 4 are under examination.
Election/Restrictions
10. Applicant’s election without traverse of Group 1 (claims 3 and 4) and election without traverse of acute renal failure resulting from bacterial sepsis as species of acute renal failure in the reply filed on 7/21/2026 is acknowledged. The requirement is made FINAL in this office action.
Group 1 is drawn to a method of prevent or treat an acute renal failure, comprising administering glutathione trisulfide or a pharmacologically acceptable salt thereof to a subject in need thereof. A search was conducted on the elected species; and prior art was found. Claims 3 and 4 are examined on the merits in this office action.
Claim Interpretations
11. With regards to a method of preventing acute renal failure in a subject in need thereof, in the instant case, the instant specification fails to define the subject that is in need of preventing acute renal failure. Therefore, for the purpose of compact prosecution and in the broadest reasonable interpretation, the Examiner is interpretating any subject is one that is in need of preventing acute renal failure. Such interpretation applies to all the rejections set forth below.
Objections
12. The specification is objected to for the following minor informality: The specification recites the term “suprresing” on page 1, line 18 of instant specification. This appears to be a typo. Applicant is required to correct this error.
Please note: The specification has not been checked to the extent necessary to determine the presence of all possible error. Applicant's cooperation is required in correcting any errors of which applicant may become aware in the specification (see MPEP § 608.01).
13. The drawings are objected to for the following minor informality:
Figures 1 and 2: It is unclear what 1, 2, or 3 in these figures means.
Figures 3a, 3b, 4a and 4b: legends for X-axis and Y-axis are missing.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
14. Claim 3 is objected to for the following minor informality: Applicant is suggested to amend claim 3 as “A method of preventing or treating acute renal failure in a subject in need thereof, wherein the method comprises administering to the subject an effective amount of glutathione trisulfide or a pharmacologically acceptable salt thereof”.
15. Claim 4 is objected to for the following minor informality: Applicant is suggested to amend claim 4 as “The method according to claim 3, wherein the acute renal failure is resulting from at least one condition selected from the group consisting of …and drug nephritis; or is associated with renal ischemia or renal ischemia reperfusion”.
Rejections
Claim Rejections - 35 U.S.C. § 112 paragraph (a)
Scope of Enablement
16. The following is a quotation 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 35 U.S.C. 112 (pre-AIA ), first paragraph:
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.
17. Claims 3 and 4 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification while being enabling for a method of treating acute renal failure, comprising administering glutathione trisulfide or a pharmacologically acceptable salt thereof to a subject in need thereof, does not reasonably provide enablement for a method of preventing acute renal failure, comprising administering glutathione trisulfide or a pharmacologically acceptable salt thereof to a subject in need thereof. The specification does not enable any person skilled in the art to which it pertains to make and/or use the invention commensurate in scope with the claims.
The factors to be considered in determining whether a disclosure meets the enablement requirement of 35 U.S.C. 112, first paragraph, have been described in In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988). Among these factors are: (1) the nature or the invention; (2) the state of the prior art; (3) the relative skill of those in the art; (4) the predictability or unpredictability of the art; (5) the breadth of the claims; (6) the amount of direction or guidance presented; (7) the presence or absence of working examples; and (8) the quantity of experimentation necessary. When the above factors are weighed, it is the Examiner’s position that one skilled in the art could not practice the invention without undue experimentation.
(1) The nature of the invention and (5) The breadth of the claims:
The instant claims 3 and 4 are drawn to a method of prevent or treat an acute renal failure, comprising administering glutathione trisulfide or a pharmacologically acceptable salt thereof to a subject in need thereof.
With regards to “prevent”, the instant specification fails to define it.
The term “prevent” implies a perfect blocker from getting acute renal failure.
(2) The state of the prior art and (4) The predictability or unpredictability of the art:
With regarding to using glutathione trisulfide or a pharmacologically acceptable salt thereof to prevent acute renal failure, the art is unpredictable.
The Acute kidney injury document (from https://www.mayoclinic.org/diseases-conditions/kidney-failure/symptoms-causes/syc-20369048, 2026, enclosed pages 1-3) teaches there are many causes of acute kidney injury (AKI, synonym of acute kidney failure or acute renal failure); and various means to reduce the risk of getting AKI, for example, pages 1-3, Sections “Causes” and “Prevention”. However, the Acute kidney injury document is silent about how to completely block getting acute renal failure.
(3) The relative skill of those in the art:
The related skill of those in the art is high.
(6) The amount of direction or guidance presented and (7) The presence or absence of working examples:
With regarding to using glutathione trisulfide or a pharmacologically acceptable salt thereof to prevent acute renal failure, the instant specification fails to provide any guidance on how to prevent acute renal failure. There is no clear guidance as to how to determine the patient population. Acute renal failure can be treated once it is diagnosed; however, it cannot be prevented since the patient population is unknown.
Taken all these together, the instant specification does not enable any person skilled in the art to which it pertains to make and/or use the invention commensurate in scope with the claims. There is a lack of adequate guidance from the specification or prior art with regard to the actual method of using glutathione trisulfide or a pharmacologically acceptable salt thereof to prevent acute renal failure. Applicant's limited disclosure is noted but is not sufficient to justify claiming a method of using glutathione trisulfide or a pharmacologically acceptable salt thereof to prevent acute renal failure.
(8) The quantity of experimentation necessary:
Considering the state of prior arts and the disclosure in instant specification, one of ordinary skill in the art would be burdened with undue experimentation for a method of using glutathione trisulfide or a pharmacologically acceptable salt thereof to prevent acute renal failure.
Claim Rejections - 35 U.S.C. § 103
18. 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 of this title, 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.
19. The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
20. Claims 3 and 4 are rejected under 35 U.S.C. 103 as being unpatentable over Mir et al (Biomedicine & Pharmacotherapy, 2018, 100, pages 304-315) in view of Tawarayama et al (OCULAR IMMUNOLOGY AND INFLAMMATION, 2020, pages 1-11).
The instant claims 3 and 4 are drawn to a method of prevent or treat an acute renal failure, comprising administering glutathione trisulfide or a pharmacologically acceptable salt thereof to a subject in need thereof.
Mir et al, throughout the literature, teach sepsis-induced acute kidney injury (AKI, synonym of acute kidney failure or acute renal failure) is responsible for 70–80% mortality in intensive care patients due to elevated levels of lipopolysaccharide (LPS) caused by gram-negative infections; and a method of treating AKI resulting from bacterial sepsis in a subject in need thereof, wherein the method comprises administering to the subject ferulic acid (FA), and wherein FA upregulates antioxidant defenses and suppresses inflammatory events by inhibiting NFκB activation, for example, Abstract; page 305, left column, the 2nd and 3rd paragraphs; pages 306-307, Sections “3.2. Ferulic acid ameliorates oxidative stress in LPS challenged mice” and “3.6. Ferulic acid attenuates LPS-induced renal inflammation”; pages 308-309, Section “3.9. Ferulic acid inhibits TLR-4 mediated nuclear translocation of NF-κB (p65) and IκBα degradation in renal tissue”; and page 311, left column, the 1st paragraph in Section “4. Discussion”. It reads on acute renal failure resulting from bacterial sepsis as the elected species of acute renal failure; and meets the limitation of the subject recited in instant claims 3 and 4.
The difference between the reference and instant claims 3 and 4 is that the reference does not teach treating acute renal failure resulting from bacterial sepsis with glutathione trisulfide or a pharmacologically acceptable salt thereof.
However, Tawarayama et al, throughout the literature, teach that similar to FA taught in Mir et al, glutathione trisulfide (GSSSG) attenuates LPS-induced inflammatory gene expression via preventing the activation of the nuclear factor-kappa B p65 subunit; GSSSG-mediated anti-oxidative functions may partially contribute to preventing inflammatory gene upregulation in LPS-treated cells; GSSSG is an endogenous modulator of the inflammatory responses in organisms and plays an important role in attenuating excessive inflammation, thereby preventing inflammation-induced tissue damage; and administration of exogenous GSSSG as a promising treatment for inflammation-associated diseases, for example, Abstract; Figures 2, 3 and 4; pages 6-9. Sections “Discussion” and “Conclusion”.
Therefore, it would have been obvious to one of ordinary skilled in the art to combine the teachings of Mir et al and Tawarayama et al to develop a method of treating acute kidney injury (AKI, synonym of acute kidney failure or acute renal failure) resulting from bacterial sepsis in a subject in need thereof, wherein the method comprises administering to the subject GSSSG.
One of ordinary skilled in the art would have been motivated to combine the teachings of Mir et al and Tawarayama et al to develop a method of treating acute kidney injury (AKI, synonym of acute kidney failure or acute renal failure) resulting from bacterial sepsis in a subject in need thereof, wherein the method comprises administering to the subject GSSSG, because Tawarayama et al, throughout the literature, teach that similar to FA taught in Mir et al, glutathione trisulfide (GSSSG) attenuates LPS-induced inflammatory gene expression via preventing the activation of the nuclear factor-kappa B p65 subunit; GSSSG-mediated anti-oxidative functions might partially contribute to preventing inflammatory gene upregulation in LPS-treated cells; GSSSG is an endogenous modulator of the inflammatory responses in organisms and plays an important role in attenuating excessive inflammation, thereby preventing inflammation-induced tissue damage; and administration of exogenous GSSSG as a promising treatment for inflammation-associated diseases. The method developed from the combined teachings of Mir et al and Tawarayama et al is a simple substitution of one known element for another to obtain predictable results (see MPEP § 2143 I B).
A person of ordinary skilled in the art would have reasonable expectation of success in combining the teachings of Mir et al and Tawarayama et al to develop a method of treating acute kidney injury (AKI, synonym of acute kidney failure or acute renal failure) resulting from bacterial sepsis in a subject in need thereof, wherein the method comprises administering to the subject GSSSG.
Obviousness Double Patenting
21. 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 claims at issue 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); and 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 a nonstatutory double patenting ground provided the reference application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO internet Web site contains terminal disclaimer forms which may be used. Please visit http://www.uspto.gov/forms/. The filing date of the application will determine what form 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 http://www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
22. Claim 3 is provisionally rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-5 and 9-17 of co-pending Application No. 19/131076.
23. Instant claim 3 is drawn to a method of prevent or treat an acute renal failure, comprising administering glutathione trisulfide or a pharmacologically acceptable salt thereof to a subject in need thereof.
24. Claims 1-5 and 9-17 of co-pending Application No. 19/131076 are drawn to a prophylactic or therapeutic agent for acute kidney injury induced by an anti-cancer agent, comprising at least one selected from the group consisting of glutathione trisulfide and a pharmacologically acceptable salt thereof and other agents; a method for preventing or treating acute kidney injury induced by an anti-cancer agent, comprising administering to a patient in need thereof with such compound; and a method for treating cancer, comprising administering to a patient in need thereof, an anti-cancer agent and at least one compound selected from the group consisting of glutathione trisulfide and a pharmacologically acceptable salt thereof and other agents. This is a provisional obviousness-type double patenting rejection because the conflicting claims have not in fact been patented.
25. Claim 3 is rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-4 and 7 of US patent 12758524 B2 (issued patent of Application No. 18/572109).
26. Instant claim 3 is drawn to a method of prevent or treat an acute renal failure, comprising administering glutathione trisulfide or a pharmacologically acceptable salt thereof to a subject in need thereof.
27. Claims 1-4 and 7 of US patent 12758524 B2 are drawn to method for suppressing dopamine decomposition comprising administering (i) a trisulfide compound and (ii) a drug utilized in dopamine replacement therapy or a pharmaceutically acceptable salt thereof to a patient having Parkinson's disease, wherein the trisulfide compound is (a) glutathione trisulfide or a pharmaceutically acceptable salt thereof, (b) lipoic acid trisulfide or a pharmaceutically acceptable salt thereof or a cyclodextrin clathrate thereof, (c) pantethine trisulfide or a pharmaceutically acceptable salt thereof, or (d) N,N'-diacetyl-L-cysteine trisulfide or a pharmaceutically acceptable salt thereof.
In view of the combined teachings of claims 1-4 and 7 of US patent 12758524 B2, it would have been obvious to one of ordinary skilled in the art to develop a method for suppressing dopamine decomposition comprising administering (i) a trisulfide compound and (ii) a drug utilized in dopamine replacement therapy or a pharmaceutically acceptable salt thereof to a patient having Parkinson's disease, wherein the trisulfide compound is glutathione trisulfide or a pharmaceutically acceptable salt thereof. This is the same as a method of preventing acute renal failure in a subject in need thereof recited in instant claim 3.
28. For the same/similar reasoning/rational as the rejection set forth in Sections 25-27 above, instant claim 3 is provisionally rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 8, 9, 11, 12, 14 and 15 of co-pending Application No. 18/689734; claims 7-13 of co-pending Application No. 18/836961; claims 1-7 of co-pending Application No. 19/113849; and claims 9, 10, 12-14 and 16 of co-pending Application No. 19/159449.
These are all provisional obviousness-type double patenting rejections because the conflicting claims have not in fact been patented.
Please note: Instant application and co-pending Application No. 18/836961 share the same applicant (KYOWA BAKKO BIO CO., LTD).
29. Claims 3 and 4 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-18 of US patent 11186610 B2 and in view of Mir et al (Biomedicine & Pharmacotherapy, 2018, 100, pages 304-315) and Tawarayama et al (OCULAR IMMUNOLOGY AND INFLAMMATION, 2020, pages 1-11).
30. Instant claims 3 and 4 are drawn to a method of prevent or treat an acute renal failure, comprising administering glutathione trisulfide or a pharmacologically acceptable salt thereof to a subject in need thereof.
31. Claims 1-18 of US patent 11186610 B2 are drawn to a crystal of glutathione trisulfide dihydrate; and methods of making such crystal of glutathione trisulfide dihydrate.
32. The difference between claims 1-18 of US patent 11186610 B2 and instant claims 3 and 4 is that claims 1-18 of US patent 11186610 B2 do not teach applying the crystal of glutathione trisulfide dihydrate in a method recited in instant claims 3 and 4.
However, in view of the combined teachings of Mir et al and Tawarayama et al as set forth in Section 20 above, it would have been obvious to one of ordinary skilled in the art to apply the crystal of glutathione trisulfide dihydrate recited in claims 1-18 of US patent 11186610 B2 and develop the method recited in instant claims 3 and 4.
Please note: Instant application and US patent 11186610 B2 share the same applicant (KYOWA BAKKO BIO CO., LTD).
Conclusion
No claim is allowed.
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/LI N KOMATSU/Primary Examiner, Art Unit 1658
