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 .
Application Status
The preliminary amendment filed on 12/08/2023 is acknowledged. Claims 1, 6, 11, 13-16, 19-28, 30, 39, 41, 43, 45-46 and 49 are currently pending and under consideration.
Information Disclosure Statement
The information disclosure statements filed on 12/08/2023, 1/17/2025 and 2/03/2025 are acknowledged and have been considered except where lined through.
Claim Objections
Claim 28 is objected to because of the following informalities: Claim 28 is confusing. It is suggested that Applicants consider amending the claim to recite “… wherein the composition comprises a unit dosage form of a therapeutic amount of the compound and/or the composition further comprises an anticancer agent.” Appropriate correction is required.
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.
Claim 16 is 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 16, claim 16 depends from claim 1 and recites the limitation “…wherein R2 is H and/or R1 is –(CH2)mRb.” However, neither claim 16 or claim 1 defines what “m” is.
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.
Claims 30, 39, 41, 43, 45-46 and 49 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 an in vitro method of inhibiting a cancer cell by administering a compound having the formula IA
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, wherein the ring bearing X1, X2 and X3 is
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, does not reasonably provide enablement for an in vivo method of treating cancer comprising administering any and all compounds encompassed by a compound of formula IA as claimed in claim 1. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
The criteria for enablement set out in the In re Wands, MPEP 2164.01(a), considers the following factors:
Breadth of the Claims
The instant claims are directed toward both an in vitro and in vivo method of treating cancer comprising administering a administering a compound having the formula IA
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, wherein the ring bearing X1, X2 and X3 is can be O or N and the dash lines represent a single or double bond.
Thus, the breadth of the claims is great.
Level of Skill in Art
The level of skill in the art is a clinician or an artisan with a PhD.
Working Examples
The specification provides a small molecule microarray screening and hit identification of small molecules that bind MYCN G4, wherein 14 compounds were identified of differing chemical structures (Example 2). In particular, the specification teaches that only one compound referred to as MY-1 having the structure
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specifically bound to MYCN G4 and notes that it was because of its unique structure (Example 2, last sentence, page 83). In addition to the microarray screening, the specification teaches a structure activity relationship study was performed by suing a series of analogs of MY-1 (Example 5). Specifically, the specification teaches that most analogs contained an altered side chain R since it is believed that the pyrrolidine group of MY-1 played an role in binding G4 and that the heterocyclic core of MY-1 facilitates MYCN G4 recognition (Example 5, see Table 3 for compounds). The specification further provides various binding assays (see for example, Example 13). The specification does not specifically teach any in vivo examples.
State of the Prior Art/Predictability in the art
The specification teaches that the MYC family of genes encode transcription factors that broadly govern and amplify gene expression, wherein MYCN is often overexpressed or mutated in cancers such as neuroblastoma and small cell lung cancers (page 1, lines 20-25). The specification further teaches that molecules that control or inhibit the N-Myc protein and other proteins involved in cancers are of interest as anticancer agents; however, as a transcription factor, the N-Myc protein is classically considered “undruggable” and attempts to develop ligands that target N-Myc itself, and other undruggable proteins have not been successful (page 1, lines 33-36).
Dang et al. (Nature 2017; 17: 502-508) teach that the term “undruggable” was coined to describe proteins that could not be targeted pharmacologically, wherein many desirable targets in cancer fall into this category, including the RAS and MYC oncogenes, and pharmacologically targeting these intractable proteins is a key challenge in cancer research that requires innovation and the development of new technologies (Abstract).
Whitfield et al. (Frontiers in Cell and Developmental Biology 2017; 5 (10): 1-13) teaches that Myc is recognized as a “most wanted” target for cancer therapy, but has for many years been considered undruggable, mainly due to its nuclear localization, lack of a defined ligand binding site, and physiological function essential to the maintenance of normal tissues (abstract). Whitfield further teaches that one strategy employed for inhibiting MyC is through G-quadruplex stabilizers. In particular, Whitfield et al. teach that a number of small molecule ligands were shown to stabilize such G-quadruplexes in the myc gene, thus repressing its transcription (page 2, 2nd column, (G-quadruplex stabilizers).
At the time of filing, no prior can be found using any compound encompassed by
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, wherein the ring bearing X1, X2 and X3 is can be O or N and the dash lines represent a single or double bond.
With regards to small molecule inhibitors of MyC through G-quadruplex stabilizers, Felsenstein et al. (ACS Chem. Biol. 2016; 11: 139-148) teaches small molecule microarrays which enable the identification of a selective quadruplex-binding inhibitor of MYC expression (Title). Specifically, Felsenstein et al. teach that the compound has the structure
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(abstract)
Thus, in view of the prior art, targeting MYC-N for the treatment of cancer in unpredictable.
Direction and Guidance
In view of the examples provided in the specification which do not appear to provide any in vivo examples, there is minimal direction provided by the inventor.
Quantity of Experimentation
In view of the unpredictability of the art in targeting the “undruggable” MYC with pharmacologically active agents, it is an undue amount of experimentation.
Thus, while being enabling for an in vitro method of inhibiting a cancer cell by administering a compound having the formula IA
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, wherein the ring bearing X1, X2 and X3 is
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, does not reasonably provide enablement for an in vivo method of treating cancer comprising administering any and all compound encompassed by a compound of formula IA as claimed in claim 1.
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, 6, 11, 13-16, 19-20, 24 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by CAS Registry No. 1358960-59-4 (entered STN on 2012-03-01).
CAS Registry No. 1358960-59-4 has the structure
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which reads on the instant compound of formula IA when X1and X2 are N, X3 is O, R2 is H, R1 is an aliphatic linker, Rb is a heteroaliphatic, R3 is a heteroaliphatic.
Claim(s) 1, 6, 11, 13-16, 19-21 and 24 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by CAS Registry No. 1358396-79-8 (entered STN on 2012-02-29).
CAS Registry No. 1358396-79-8 has the structure
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which reads on the instant compound of formula IA when X1and X2 are N, X3 is O, R2 is H, R1 is an aliphatic linker, Rb is a heteroaliphatic, R3 is a halo.
Conclusion
Claims 22, 25-26 objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Claim 27 is free of the prior art and allowable.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. CAS Registry No. 1358325-41-3 (entered STN on 2012-02-29).
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BRANDON J FETTEROLF whose telephone number is (571)272-2919. The examiner can normally be reached M-F 6AM-4PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey S Lundgren can be reached at 571-272-5541. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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BRANDON J. FETTEROLF, PHD
Primary Patent Examiner
Art Unit 1626
/BRANDON J FETTEROLF/Primary Examiner, Art Unit 1626