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 .
Priority
The instant application is a 371 National Stage Entry of PCT/EP2021/086038 filed on December 15, 2021.
Status of Claims
Acknowledgement is made of amended (1, 9, 13-15, 18-21), previously presented (2, 4-8, 11-12, 16, 22), cancelled (3, 10, 17), and new (23) claims filed on November 24, 2025. Claims 1-2, 4-9, 11-16, 18-23 are pending in instant application. Claims 5, 7, 20 are withdrawn. Claims 1-2, 4, 6, 8-9, 11-16, 18, 19, 21-23 are presently examined.
Information Disclosure Statement
The information disclosure statement filed on June 15, 2023; August 13, 2024; August 22, 2024 have been considered except where lined through.
Election/Restrictions
Restriction
Acknowledgement is made of Applicant’s election with traversal in the restriction/election requirement in the reply filed on November 24, 2025. The restriction requirement between groups, as set forth in the Office action mailed on October 1, 2025, has been reconsidered in view of the traversal of claims to the elected invention pursuant to MPEP § 821.01. Since Applicant elected Group I (method of treating), a search of utility of compounds of Formula I inevitably uncovered compounds of Formula I, the restriction requirement between groups is hereby withdrawn.
In view of the above noted withdrawal of the restriction requirement, applicant is advised that if any claim presented in a divisional application is anticipated by, or includes all the limitations of, a claim that is allowable in the present application, such claim may be subject to provisional statutory and/or nonstatutory double patenting rejections over the claims of the instant application.
Once a restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable. See In re Ziegler, 443 F.2d 1211, 1215, 170 USPQ 129, 131-32 (CCPA 1971). See also MPEP § 804.01.
Election of Species
Applicant’s traversal of the species election is not fully persuasive. Upon further consideration, the species election requirement of the method of treatment is withdrawn. However, compounds of Formula I do not make a contribution over the prior art.
Applicant in the reply elected:
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The Examiner notes the name and structure of the compound do not match. The structure appears to be (2E)-2-{[2-(morpholin-4-yl)-2-oxoethyl]sulfanyl}-4,5,6,7,8,9-hexahydro-1H-1,3-diazonin-3-ium chloride.
Moreover, Applicant states the elected species is TTC-01, which in claim 21 appears to be (see also below Claim Objections and 112(b) Rejection):
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the above compound being 2-[(3aS,7aS)-3a,4,5,6,7,7a-hexahydro-1H-1,3-benzodiazol-2-ylsulfanyl]-1-(morpholin-4-yl)ethan-1-one hydrochloride, or alternatively (3aS,7aS)-2-{[2-(morpholin-4-yl)-2-oxoethyl]sulfanyl}-3a,4,5,6,7,7a-hexahydro-1H-1,3-benzodiazol-3-ium chloride.
11/24/25 Remarks Elected Species
Claim 21 TTC-01
CAS# 2790482-53-8
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The Examiner is taking the stance that the elected species is understood to be CAS# 2790482-53-8 which comprises hydrogen chloride, or CAS# 2790482-52-7, or CAS# 447410-08-4, because the structure depicted in the 11/24/25 Remarks does not read on instant Formula I. Claims 1-2, 4, 6, 8-9, 11-16, 18, 19, 21-23 read on the species.
Claims 5, 7, 20 are 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.
Compact prosecution: During the search and examination of the originally elected species, art pertinent to other non-elected species was incidentally discovered. Although examination has not been extended beyond the non-elected species identified above per MPEP § 803.02, as a courtesy to the Applicant, this art has been applied below.
Claims 1-2, 4, 6, 8-9, 11-16, 18, 19, 21-23 presently examined.
Claim Interpretation
Regarding claims 1, 18, while the claims recite “R1 and R2 together form a 5- or 6-membered heterocyclic ring”, they do not specify if the ring is substituted, unsubstituted, or optionally substituted. The Examiner is taking the position the ring may be optionally substituted given the species of claim 21 appear to include substituted rings such as
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.
Regarding claims 8, 12, and 15, the claims recite “and/or”.
Claim 8’s limitations may be satisfied by the structural limitation combinations:
(i) or (ii) and (iii)
(i) and (ii) or (iii)
(i) or (ii) or (iii)
(i) and (ii) and (iii)
Likewise, claim 12 can be satisfied by any combination of “and” or “or” for the structural limitations (i)-(v). In their broadest interpretations, the claim limitations are met when only one of the and/or structural alternatives are met.
Similarly, claim 15 can be satisfied by:
regulating glycolytic metabolism
treating a neurodegenerative disease
treating inflammation
treating a neurodegenerative disease and inflammation.
Claim Objections
Claim 21 is objected to because of the following informalities:
The structures and structure names are not discernable (see below 35 USC 112(b) Rejection).
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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 1-2, 4, 6, 8-9, 11-13, 21-23 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.
Regarding claim 1, the claim states “a method of treating a subject in need thereof” which is indefinite because “a subject in need” is not defined in the specification. It is unclear what is included or excluded by “in need” or “a subject”. Claims 2, 4-6, 8-9, 11-13, 21-23 do not rectify the issue of indefiniteness and are thus included in instant rejection. For the purposes of applying art, any known utility of an encompassed compound will read on “in need”, and anything including cells or mammals will read on “a subject”.
Regarding claim 4, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Regarding claim 21, the claim recites indiscernible structures and names of structures. Non-exhaustive examples include:
it is not clear what
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says.
it is not clear if
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is two separate structures, or an omitted bond attempting to show one structure.
it is not clear if
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truly has a
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moiety or is meant to be
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.
it is not clear if
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is a complete structure, and if
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is meant to be a phenyl or not.
it is not clear if
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truly has a
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moiety or is meant to be
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, as shown the structure does not have A as a non-aromatic ring, an aromatic ring, or a double bond and thus does not read on Formula I (see below 35 USC 112(d) Rejection).
The defined species listed in the claim are not clear to one of skill in the art. All structures and names must be clear and complete.
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.
Claims 11, 21 are 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.
Regarding claim 11, the claim depends from instant claim 9 which states “wherein the 5- or 6-memebered heterocyclic ring comprised 1 N atom and at least one additional heteroatom selected from the group consisting of: N, S, and O.” emphasis added. Claim 11 states “piperidine group” which does not fulfill the limitations of claim 9.
Regarding claim 21, the claim includes compounds that do not read on claim 1 Formula I.
For example:
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does not have A as a non-aromatic ring, an aromatic ring, or a double bond
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) 1-2, 4, 6, 8-9, 11-12, 18, 19, 22 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by WO 2009/149054 A1 to Byrd et. al.1
Regarding claims 1-2, 4, 6, 8-9, 11-12, 18, 19 a compound of Formula I, Byrd teaches compound 8 which reads on instant Formula I when A is an aromatic ring, specifically phenyl, X is NR3 and R3 is H, Y is S, Z is (CR6R7)n and n is 1, R6 is H and R7 is H, R1 and R2 form a 6 membered heterocyclic ring specifically piperazine, substituted with 4-fluorophenyl
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(see Byrd table 1, page 54).
Byrd Compound 8
Instant Formula I
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Regarding claims 1 a method of treating a subject in need, Byrd teaches methods of treating viral infections by administering therapeutically effective amounts of the disclosed compounds to mammals in need thereof (see Byrd at claim 8).
Regarding claim 22 and a composition, Byrd teaches a composition comprising the disclosed compound and a pharmaceutically acceptable carrier (see Byrd claim 1).
Claim(s) 18, 19 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by STN2.
Regarding claims 18 and 19 and a compound of Formula I, STN teaches CAS# 447410-08-4, the same as instant compound 1/TTC-01 and TTC-02 (see instant spec at p. 6) which reads on Formula I when X is NR3 and R3 is H, A is a non-aromatic ring, Y is S, Z is (CR6R7)n and n is 1, R6 is H, R7 is H, R1 and R2 together form a 6 membered heterocyclic ring specifically morpholine.
CAS# 447410-08-4
Instant Formula I
Instant Compound 1
BAS-2
TTC-01 and TTC-02
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Claim(s) 1, 4, 8, 12, 18, 19, are rejected under 35 U.S.C. 102(a)(1) as being anticipated by WO 2013/147160 A1 to Morita et. al.3
Regarding claims 1, 4, 8, 12, 18, 19, and a compound of Formula I, Morita teaches CAS# 1463432-17-8 which reads on instant Formula I when A is a double bond, X is NR3 R3 is alkyl specifically methyl, Y is CR4R5, R4 is H, R5 is H, Z is (CR6R7)n and n is 1 R6 is H and R7 is H, R1 and R2 together form a substituted 6-membered heterocyclic ring specifically
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(see Morita at p. 6).
Morita
CAS# 1463432-17-8
Instant Formula I
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Regarding claim 1 and a method of treating a subject, Morita teaches the disclosed compounds are analgesics that can be administered to mammals for pain (see Morita Trans. at p. 47).
Claim(s) 1, 2, 8-9, 11-12, 15-16 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by WO 2013/128465 A1 to Rao et. al.4 as evidenced by Lebovitz5.
Regarding claims 1, 2, 8-9, 11-12 and a compound of Formula I, Rao teaches compounds that read on instant Formula I such as CAS# 1197861-17-8 (see Rao at p. 263). CAS# 1197861-17-8 reads on instant Formula I when A is an aromatic ring, X is S, Y is CR4R5, R4 is H, R5 is H, Z is (CR6C7)n and n is 1, R6 is H, R7 is H, R1 and R2 together form a 6-membered heterocyclic ring specifically a morpholine group, more specifically
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.
Rao
CAS# 1197861-17-8
Instant Formula I
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Regarding claims 1, 15 and a method of treating, Rao teaches the disclosed compounds can be used in methods of treating diabetes, hyperglycemia, hyperinsulinemia, etc (reading on instant “regulating glycolytic metabolism”), and inflammatory diseases (see Rao at claim 16).
Regarding claim 16 and further administering a metabolic inhibitor, Rao teaches the compound may be administered in combination with an adjuvant such as an alpha-glucosidase inhibitor (see Rao claim 20). Lebovitz explains alpha-glucosidase inhibitors are metabolism inhibitors (see Lebovitz at “Metabolic Parameters”).
Claim(s) 18-19 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Hongxia6.
Regarding claims 18-19 and compounds of Formula I, Hongxia teaches compounds 4a-4q as anticancer agents, including CAS# 392714-60-2 (compound 4k) (see Hongxia at Title and pp. 8-12). CAS# 392714-60-2 reads on Formula I when X is NR3, R3 is H, Y is S, Z is (CR6C7)n and n is 1, R6 is H, R7 is H, A is aromatic ring specifically phenyl, R1 and R2 together form a 6-membered heterocyclic ring specifically phenyl-substituted piperazine.
Hongxia Compound 4k
CAS# 392714-60-2
Instant Formula I
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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.
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.
Claim(s) 18, 19 are rejected under 35 U.S.C. 103 as being obvious over STN as applied to claims 18, 19 above.
Regarding claims 18 and 19 and a compound of Formula I, STN teaches CAS# 447410-08-4, the same as instant compound 1/TTC-01 and TTC-02 (see instant spec at p. 6) which reads on Formula I when X is NR3 and R3 is H, A is a non-aromatic ring, Y is S, Z is (CR6R7)n and n is 1, R6 is H, R7 is H, R1 and R2 together form a 6 membered heterocyclic ring specifically morpholine.
CAS# 447410-08-4
Instant Formula I
Instant Compound 1
BAS-2
TTC-01 and TTC-02
Stereoisomer
Elected Species
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The prior art differs from the elected species as follows: STN does not specify stereochemistry of CAS# 447410-08-4, the line angle structure indicating a mixture of stereoisomers.
However, it would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to arrive at the instantly claimed invention with a reasonable expectation of success in view of the prior art for at least the following reason(s):
Per MPEP § 2144.09(I)-(II), “[a] prima facie case of obviousness may be made when chemical compounds have very close structural similarities and similar utilities” because “[c]ompounds which are…isomers…are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties” (see, e.g., MPEP § 2144.09(I)-(II)), and the Court has stated that “[i]f a person of ordinary skill can implement a predictable variation, § 103 likely bars its patentability.” KSR, 127 S.Ct. at 1740. See also Aventis Pharma Deutschland v. Lupin Ltd., 499 F.3d 1293, 84 USPQ2d 1197 (Fed. Cir. 2007) (5(S) stereoisomer of ramipril obvious over prior art mixture of stereoisomers of ramipril.).
Furthermore, it is well-within the ordinary skill in art to isolate a stereoisomer of a known compound taught by the prior art.
Therefore, an artisan would arrive at the same invention as presently claimed for reasons taught in the prior art.
Claim 14 is rejected under 35 U.S.C. 103 as being obvious over Rao as evidenced by Lebovitz as applied to claims 1, 2, 8-9, 11-12, 15-16 above in further view of Mitchison et. al.7
Regarding claim 14 and a method of treating cancer, Rao teaches the disclosed compounds can be selectively toxic or more toxic to “rapidly proliferating cells, e.g. cancerous tumors, than to normal cells” (see Rao at p. 70 lines 9-13) reading on instant “treating cancer”.
The prior art differs from the elected species as follows: While Rao teaches the compounds are selectively or more toxic to cancerous tumors than to normal cells, Rao does not specify “treating cancer”.
However,
Mitchison teaches “cancer chemotherapy agents are broadly categorized into “targeted” and “cytotoxic” drugs” and “cytotoxic drugs work by damaging DNA or microtubules and are believed to gain much or all of their specificity in the human body from their ability to preferentially kill rapidly proliferating cells” (see Mitchison at p, 1 left col ¶1).
Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to arrive at the instantly claimed invention with a reasonable expectation of success in view of the prior art for at least the following reason(s):
Per MPEP § 2143(I)(D), a prima facie case of obviousness exists for applying a known technique to a known method or product ready for improvement to yield predictable results. It would have been obvious to an artisan to recognize compounds of Rao as suitable cytotoxic chemotherapy agents because Rao’s teachings (i.e. selectively toxic or more toxic to rapidly proliferating cells) fulfill the chemotherapy definition as taught by Mitchison (i.e. preferentially killing rapidly proliferating cells). An artisan would readily recognize a chemotherapy agent would be suitable for treating cancer in a patient as taught by Mitchison.
Furthermore, it is well-within the ordinary skill in art to use a known chemotherapy agent for use in treating cancer in a subject as taught by the prior art.
Therefore, an artisan would arrive at the same invention as presently claimed for reasons taught in the prior art.
Claim(s) 1-2, 4, 6, 8-9, 11-12, 14, are rejected under 35 U.S.C. 103 as being obvious over Hongxia as applied to claims 18-19 above.
The claims differ from the prior art as follows: While Hongxia teaches compounds of Formula I as anti-cancer agents, Hongxia does not specify administering to a subject.
However, it would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to arrive at the instantly claimed invention with a reasonable expectation of success in view of the prior art for at least the following reason(s):
Per MPEP § 2143(I)(D), a prima facie case of obviousness exists for applying a known technique to a known method or product ready for improvement to yield predictable results. It would have been obvious to an artisan to administer a known anti-cancer agent to a subject with cancer because it would be performing its art-recognized function (treating cancer) in order to alleviate the subject’s condition (having cancer).
Furthermore, it is well-within the ordinary skill in art to use a known anti-cancer agent for use in treating cancer in a subject for the same purpose (treating cancer) as taught by the prior art.
Therefore, an artisan would arrive at the same invention as presently claimed for reasons taught in the prior art.
Conclusion
Claim 21 is objected to.
Claims 1-2, 4, 6, 8-9, 11-16, 18-19, 21-23 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SOPHIA J REILLY whose telephone number is (703)756-5669. The examiner can normally be reached 9:00 am - 5:00 pm EST M-F.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, KORTNEY KLINKEL can be reached at 571-270-5239. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/S.R./ Examiner, Art Unit 1627
/JENNIFER A BERRIOS/ Primary Examiner, Art Unit 1613
1 Cite No. 13 in the IDS filed 8/22/24. Hereinafter Byrd.
2 CAS 447410-08-4 CAS Registry File Accessed December 9, 2025 from STN, entered into STN September 6, 2002. Hereinafter STN.
3 Filed March 29, 2013. Published October 3, 2013. Hereinafter Morita. Machine Translation of WO 2013147160 A1, Translated by Patent Translate Espacenet.org on 12/9/25, 149 pages, Hereinafter Morita Trans.
4 Filed December 21, 2013. Published September 6, 2013. Hereinafter Rao.
5 Lebovitz. "ALPHA-GLUCOSIDASE INHIBITORS" Endocrinology and Metabolism Clinics of North America 1997, 26, 3, 539-551. DOI: 10.1016/S0889-8529(05)70266-8. Abstract Only.
6 Hongxia et. al. "Design and Syntheses Biological Evaluations of 2-Thiol Benzimidazole Derivatives as Potential Anticancer Agent" Huaxue Tongbao, 2019, 82, 10, 909-916. DOI: 10.14159/j.cnki.0441-3776.2029.10.005. Original document received by STIC p. 1-7, translation of compound names provided by STIC p. 8-12. Machine translation of document by Google Translate on 12/10/25 p. 13-25. Hereinafter Hongxia.
7 Mitchison et. al. “The proliferation rate paradox in antimitoticchemotherapy” Molecular Biology of the Cell 2012, 23, 1, 1-6. DOI: 10.1091/mbc.e10-04-0335. Hereinafter Mitchison.