Detailed Action
The present office action is in response to the response filed on 18 May 2026.
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
Claims 1-2, 12-13, and 15-17 of the pending application have been examined on the merits. Claims 3-11, 14, and 19-21 are withdrawn (see “Response to Applicant Election” below). Acknowledgement is made of the amendments filed 18 May 2026. Acknowledgement is made of the cancellation of claims 18 and 22.
Priority
Applicants identify the instant application, Serial #: 18/438,074, filed 09 Feb 2024, as claiming priority from Provisional Application #: 63/444,639, filed 10 Feb 2023.
Information Disclosure Statement
The information disclosure statement(s) (IDS) submitted on 18 May 2026 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Response to Applicant Election
Acknowledgement is made of the remarks filed 18 May 2026.
Applicant’s election without traverse of Group I, claims 1-17, in the reply filed on 18 May 2026 is acknowledged. Applicant further elected compound 48 (below) as the species of Formula I:
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A search for the elected compound returned prior art.
Claims 3-11 and 14 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Claims 19-21 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 18 May 2026.
Examiner notes that the relevant anticipation rejection below is based upon art which was found incidental to the search for the elected species. The additional art found is relevant to the claims addressing species which have an 8-hydroxyquinoline core. This is not indicative that the entire scope of the claims has been examined; however, the following art is being applied in an effort to promote compact prosecution of the case.
Claim Objections
Claim 13 is objected to because of the following informalities: claim 13 defines variable Ra but does not have the phrase, “wherein Ra…” followed by a Markush group. 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, 12-13, and 15-17 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 claims 1-2 and 12, the phrases "for example" and “such as” renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d). Claims 13 and 15-17 are rejected for failing to remedy the deficiencies of claims 1-2 and 12.
Regarding claim 17, a pharmaceutical composition is claimed which “suppresses GLI1-mediated transcription through multiple mechanisms.” It is unclear which mechanisms are meant or how the composition can utilize the mechanisms to suppress GLI1-mediated transcription. The specification does not disclose which mechanisms for suppressing GLI-1 mediated transcription are meant by the claims. The language used and the lack of examples in the disclosure makes the claim indefinite to a person having ordinary skill in the art.
Improper Markush Grouping Rejection
Claims 1, 12, and 15-17 are rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush groupings of Ra, Rb, and Rc in Formula I:
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are improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons: The claims define as Ra and Rc as aryl, heteroaryl, or alkyl. The claims define Rb as hydrogen, aryl, heteroaryl, alkyl, haloalkyl, alkenyl, alkynyl, alkoxy, or cycloalkyl. The specification defines alkyl as including both branched and straight chain saturated aliphatic hydrocarbon groups (paragraph [0061]), alkenyl as a branched or straight chain aliphatic hydrocarbon group having one or more carbon-carbon double bonds that may occur at any stable point along the chain (paragraph [0062]), alkynyl as a branched or straight chain aliphatic hydrocarbon group having one or more carbon-carbon triple bonds that may occur at any stable point along the chain (paragraph [0063]), alkoxy as an alkyl group bound to the group it substitutes by an oxygen bridge (paragraph [0064]), cycloalkyl as a saturated hydrocarbon ring group (paragraph [0065]), heteroaryl as a stable monocyclic, bicyclic, or tricyclic aromatic ring containing 1-3 heteroatoms chosen from N, O, and S (paragraph [0067]), and haloalkyl as a branched or straight-chain alkyl group substituted with one or more halogen atoms (paragraph [0070]). The specification contains no definition of aryl. The variability of the definitions for each of the variables in the claimed structure of Formula I results in there being no shared structural similarity that a person of ordinary skill in the art would recognize. Further, based on the breadth of the structures claimed, the artisan would have no reasonable expectation of success that all compounds claimed would have the same use. Claims 15-17 are rejected for failing to remedy the deficiencies of claim 1.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
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.
Claim(s) 1-2, 12-13, and 15 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Wen et al. (Bioorg Chem, 2023, 132:106387; provided in IDS 05/18/26), hereinafter Wen.
The instantly elected group of claims are directed to compounds of Formula I:
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Applicant elected compound 48 as the species of Formula I:
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The claims are further directed towards compositions comprising a compound of Formula I and at least one pharmaceutically acceptable vehicle and/or excipient (claim 15). The composition is further limited to including a chemotherapeutic agent (claim 16).
Wen teaches reference Compound 48 which has the same structure as the instantly elected compound:
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Where R is a 4-pyrrolidinonephenyl group (pg. 6, Table 4). Compound 48 was dissolved in less than 1% DMSO to apply to ASZ001 cells (pg. 5, column 1 and pg. 15, column 1).
Applicant may rely on the exception under 35 U.S.C. 102(b)(1)(A) to overcome this rejection under 35 U.S.C. 102(a)(1) by a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application, and is therefore not prior art under 35 U.S.C. 102(a)(1). Alternatively, applicant may rely on the exception under 35 U.S.C. 102(b)(1)(B) by providing evidence of a prior public disclosure via an affidavit or declaration under 37 CFR 1.130(b).
The following anticipation rejections below are based upon art which was found incidental to the search for the elected species. The additional art found is relevant to the claims addressing species which have an 8-hydroxyquinoline core. This is not indicative that the entire scope of the claims has been examined; however, the following art is being applied in an effort to promote compact prosecution of the case.
Claim(s) 1-2, and 12 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by WO 2009/151972, hereinafter ‘972.
‘972 teaches small molecule inhibitors of botulinum serotype A neurotoxins which have the structure of Formula 1 (paragraphs [0010]-[0011]):
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Species of reference Formula 1 include CB 6636098 which anticipates the instant claims (paragraph [0071]):
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However, the entire reference provides examples which anticipate the instant claims.
Claim(s) 1-2, and 12 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Caglic et al. (J Med Chem, 2014, 57:669-676), hereinafter Caglic.
Caglic teaches compounds with inhibitory activity against botulinum neurotoxin A light chain with the following structure (Abstract and pg. 670, column 1):
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Caglic further teaches compounds 1-53 which anticipate the instant claims (pg. 671).
Claim Rejections - 35 USC § 103
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 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 1-2, 12-13, and 15-16 is/are rejected under 35 U.S.C. 103 as being obvious over Wen, further in view of Pace et al. (J Med Chem, 2016, 59:3635-3649), hereinafter Pace.
Wen teaches reference Compound 48 which has the same structure as the instantly elected compound:
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Where R is a 4-pyrrolidinonephenyl group (pg. 6, Table 4). Compound 48 was dissolved in less than 1% DMSO to apply to ASZ001 cells (pg. 5, column 1 and pg. 15, column 1). Compound 48 inhibits proliferation of ASZ001 cells with a GI50 of 19.6 µM. However, Wen does not teach a composition of Compound 48 and a chemotherapeutic agent.
Pace teaches the FDA-approved antifungal agent, itraconazole, has anticancer chemotherapeutic activity which inhibits both the angiogenesis and hedgehog signaling pathways (Abstract). Itraconazole inhibits cell proliferation of ASZ001 cells at an IC50 of 0.14 µM (pg. 3639, Table 3).
Based on the teachings of Wen and Pace, it would be prima facie obvious to one having ordinary skill in the art to combine the composition of Compound 48 with the composition of itraconazole to create a third composition to treat ASZ001 cells with a reasonable expectation of success. See In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).
Applicant may rely on the exception under 35 U.S.C. 102(b)(1)(A) to overcome this rejection under 35 U.S.C. 102(a)(1) by a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application, and is therefore not prior art under 35 U.S.C. 102(a)(1). Alternatively, applicant may rely on the exception under 35 U.S.C. 102(b)(1)(B) by providing evidence of a prior public disclosure via an affidavit or declaration under 37 CFR 1.130(b).
A reference is good not only for what it teaches by direct anticipation but also for what one of ordinary skill in the art might reasonably infer from the teachings (In re Opprecht 12 USPQ 2d 1235, 1236 (Fed Cir. 1989); In re Bode 193 USPQ 12 (CCPA) 1976). In light of the foregoing discussion, the examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103. From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Pertinent Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Kanizsai et al. (Molecules, 2018, 23:1934) is considered pertinent for teaching structure and activity of 8-hydroxyquinoline compounds. U.S. Patent No. 11,701,374 is considered pertinent for teaching 8-hydroxyquinoline derivative compounds for enhancing telomerase reverse transcriptase expression.
Conclusion
No claim is allowed.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jonathan D. Mahlum whose telephone number is (703)756-4691. The examiner can normally be reached 8:30 AM - 5:00 PM ET, M-F.
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/J.D.M./Examiner, Art Unit 1625
/Andrew D Kosar/Supervisory Patent Examiner, Art Unit 1625
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