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 .
Status of the Claims
The status of the claims are as follows:
Claims 1-4, 7, 9-12, 15, 17-19, 21-25 are pending.
Claims 2-4, 7, 9-11, 17, 19, and 21-23 are withdrawn.
Claims 1, 12, 15, 18, and 24-25 are rejected.
Response to Election/Restrictions
Applicant’s election of Group (I) drawn to claims 1-4, 7, 9-12, 15, 17-19, and 21-25 in the reply filed 07/20/2026 is acknowledged. Applicant’s election of compound 64 (Table 1), drawn to claims 1, 12, 15, 18, 24, and 25 in the reply filed 07/20/2026 is acknowledged. Claims 2-4, 7, 9-11, 17, 19, and 21-23 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. The election was made without traverse in the reply filed on 07/20/2026.
Priority
Acknowledgement is made that Instant Application 18/706,884, filed on 2024, May 02 is a National Stage entry of PCT/US2022/049091, filed on 2022, Nov. 07, which claims priority from Provisional Application 63,276,927, filed on 2021, Nov. 08.
Information Disclosure Statement
The information disclosure statement(s) (IDS) submitted on 2024, May 13; 2024, Dec. 13; and 2026, Jul. 20 is/are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement(s) is/are being considered by the examiner.
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.
Claims 1, 12, 15, 18, 24-25 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. Specifically, the claims are directed to prodrugs of compounds of Formula I.
There is insufficient written description for this claim limitation in the disclosure. M.P.E.P. § 2163 states:
"An applicant shows possession of the claimed invention by describing the claimed invention with all of its limitations using such descriptive means as words, structures, figures, diagrams, and formulas that fully set forth the claimed invention...one must define a compound by 'whatever characteristics sufficiently distinguish it'. A lack of adequate written description issue also arises if the knowledge and level of skill in the art would not permit one skilled in the art to immediately envisage the product claimed from the disclosed process."
To provide adequate written description of a claimed genus, the specification must describe sufficient distinguishing identifying characteristics of the prodrug genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, structure/function correlation, methods of making the claimed compounds or any combination thereof. In the instant case, no description of any methods of synthesizing such a broad subgenus of prodrugs for instant Formula I is disclosed.
The specification defines a “prodrug” as a compound which is convertible in vivo by metabolic means (e.g., by hydrolysis) to a disclosed compound. (page 12, paragraph 54). It is generally accepted in the art that formation of a particular prodrug or active metabolite for a given compound or series of compounds is unpredictable. As stated by Stella (Prodrugs: Challenges and Rewards, Part 1, 2007), the personnel and skills needed for a successful prodrug program “are no different from those for analog development – it takes a team. The ideal drug is one that is active, easy to formulate, well absorbed after oral dosing, has an acceptable PK profile, and is both renally cleared and metabolized to 1-2 non-toxic metabolites that are rapidly excreted after being formed. If a prodrug intervention is necessary, obviously this ideal scenario is not met. The ideal prodrug, therefore, is one that readily achieves its desired goal, is non-toxic, and breaks down efficiently and quantitatively to the drug and to known and safe by products. Like the drug discovery process, this goal is not often met.” (Page 24, Paragraph 3).
The instant specification provides no working examples of prodrugs of compounds of Formula I, which is not considered representative of the exceedingly vast number of possible prodrug combinations that is encompassed by the claims. Therefore, one of ordinary skill in the art would not reasonably conclude that Applicant was in possession of prodrugs of the compounds of Formula I at the time of filing.
Accordingly, it is not clear Applicants were in possession of the full scope of the claimed compounds at the time the invention was made. Adequate description requires more than a mere statement, or an incomplete characterization, that prodrugs are part of the invention. The skilled artisan could not “immediately envisage” the claimed prodrugs based on the description provided in the disclosure.
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.
Claim(s) 1, 12, 18, and 25 is/are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. (a)(2) as being anticipated by Naar (WO 2020/077361 A1, published 2020, Apr. 16).
Claim 1 is directed to compounds of Formula I, or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, labeled isotope, or tautomer thereof:
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Naar teaches compounds of Formula II or a pharmaceutically acceptable salt thereof (page 13, lines 16-20), and methods of their use as agents capable of binding the KIX domain of CBP or MED15 to inhibit the binding between SREBP1 and the KIX domain of MED15 or CBP (abstract).
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Compound P10 is a preferred embodiment of compounds of Formula II (page 8, right column, item 5).
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Compound P10 anticipates instant claim 1, directed to compounds of instant Formula I when:
R1 is -SR4;
R4 is C1 alkyl;
R2 is H;
Ring A is a 6-membered heteroaryl;
m is the integer 2;
both R3 are independently selected as halogen and -S(O2)R8;
R8 is C1 alkyl, wherein the alkyl is optionally substituted with one or more R9;
R9 is C6 aryl, wherein the aryl is optionally substituted with -OH;
Claim 12 is directed to compounds of Formula I, wherein R2 is H or methyl.
Compound P10 is anticipates them claim when R2 is H.
Claim 18 is directed to compounds of Formula I, wherein each R3 is independently halogen or -S(O2)R8, inter alia.
Compound P10 anticipates the claim when two R3 groups are independently selected as halogen (chlorine) and -S(O2)R8, wherein R8 is C1 alkyl that is optionally substituted with one or more R9, and wherein R9 is a C6 aryl that is optionally substituted with -OH.
Claim 25 is directed to a pharmaceutical composition comprising compounds of Formula I and one or more pharmaceutically acceptable carriers.
Naar teaches pharmaceutical compositions comprising compounds of Formula II and pharmaceutically acceptable excipients (page 15, lines 25-30).
Claim(s) 1 and 12 is/are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. (a)(2) as being anticipated by Ibrahim (Some New 4-Oxo-4H-1-Benzopyran Derivatives. J Chem Soc Pak, 1995, 17, 165-169).
Claims 1 and 12 are described above for clarity.
Ibrahim teaches the synthesis of 2-(2’-amino or acylamino-1,3,4-thiazol-5’yl)-4-oxo-4H-1-benzopyrans because of the pharmacological importance of 1,3,4-thiadiazole heterocycle (abstract). Ibrahim also discloses, for example, compound Xa (page 167, bottom).
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Compound Xa anticipates claim 1, directed to compounds of instant Formula I when:
R1 is C1 alkyl;
R2 is H;
Ring A is a 10-membered heteroaryl; and
m is the integer 0.
Compound Xa anticipates instant claim 12 when R2 is H.
Claim(s) 1, 12, 18, and 25 is/are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. (a)(2) as being anticipated by Agarwal (WO 2019/084271 A1, published 2019, May 02).
Claims 1, 12, 18, and 25 are described above for clarity.
Agarwal teaches PAPD5 inhibitors and methods of their use (abstract), wherein the some PAPD5 inhibitors are comprised of Formula III (page 137, lines 12-15):
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One example of compounds of Formula III is compound 125 (page 232, Table 5, compound 125)
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Compound 125 anticipates instant claim 1, directed to compounds of instant Formula I when:
R1 is -SR4;
R4 is C1 alkyl;
R2 is H;
Ring A is a 10-membered heteroaryl;
m is the integer 2; and
both R3 are independently selected as C1 alkyl.
Compound 125 anticipates instant claim 12 when R2 is H.
Compound 125 anticipates instant claim 18 when two R3 are independently C1 alkyl.
Regarding claim 25, Agarwal teaches pharmaceutical compositions comprising compounds of Formula III with pharmaceutically acceptable excipients (page 188, lines 7-10).
Claim(s) 1, 12, 18, and 25 is/are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. (a)(2) as being anticipated by Bemis (EP 2 316 834, published 2011, Apr. 05).
Claims 1, 12, 18, and 25 are described above for clarity.
Bemis teaches inhibitors of JAK kinases for the treatment of an autoimmune disease, a neurodegenerative disorder, or a hematologic malignancy (abstract). The inhibitors are of the general Formula IV (abstract)
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An example of the disclosed compounds of Formula IV is compound 59 (page 48)
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Compound 59 anticipates instant claim 1, directed to compounds of instant Formula I when:
R1 is -SR4
R4 is 10 membered heteroaryl.
R2 is H;
Ring A is a 5-membered heteroaryl;
m is 1; and
R3 is C1 alkyl
Compound 59 anticipates instant claim 12 when R2 is H.
Compound 59 anticipates instant claim 18 when R3 is C1 alkyl.
Regarding claim 25, Bemis teaches pharmaceutically acceptable compositions comprising compounds of Formula IV (page 2, paragraph 002). At least the solid dosage forms for oral administration comprises the active compound mixed with at least one inert, pharmaceutically acceptable excipient or carrier (page 26, paragraph 0089).
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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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.
Claim(s) 1, 12, 15, 18, and 25 is/are rejected under 35 U.S.C. 103 as being unpatentable over Agarwal.
Claims 1, 12, 18, and 25 are described above for clarity.
Agarwal teaches compound 125 as a compound derived from Formula V (page 137, lines 13-15)
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The difference between the teaching of Agarwal and the instant claim is that Agarwal fails to teach an explicit embodiment wherein the atom para to the heterocyclic carbonyl is NH.
However, Agarwal also teaches Formula VI (page 136, lines 3-5), wherein RN8 can be H (page 124, lines 28-30)
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Regarding claims 1, 12, 15, 18, and 25, one of ordinary skill in the art could have applied the rationale set forth in prong B of the KSR framework to substitute the heterocyclic oxygen atom of compound 125 with the NH of Formula VI. Said artisan would have been motivated to do so because Agarwal links the two biaryl ring systems as having similar properties.
The compound formed from the combination of compound 125 and Formula VI reads on the limitations of instant claim 1, directed to compounds of instant Formula I when:
R1 is -SR4;
R4 is C1 alkyl;
R2 is H;
Ring A is a 10-membered heteroaryl;
m is the integer 2; and
both R3 are independently selected as C1 alkyl.
The compound formed from the combined teachings of Agarwal reads on the limitations of instant claim 12 when R2 is H.
Claim 15 is directed to compounds of Formula I, wherein Ring A is selected from
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The compound formed through the combined teachings of Agarwal also renders obvious claim 15 when Ring A is selected as
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, wherein
m is 2;
Both R3 are independently C2 alkyl;
Two R3, together with the atoms to which they are attached, form a C6 aryl, wherein the aryl is optionally substituted with one or more R7; and
Two R7 are independently C1 alkyl.
The compound formed from the combined teachings of Agarwal also renders claim 15 obvious when Ring A is selected as
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, wherein
q is 2; and
Both R7 are independently R1 alkyl.
The compound formed from the combined teachings of Agarwal reads on the limitations of instant claim 18 when two R3 are independently C1 alkyl.
Regarding claim 25, Agarwal teaches pharmaceutical compositions comprising with pharmaceutically acceptable excipients (page 188, lines 7-10). Agarwal further teaches that part of the claimed invention are derivatives of the disclosed compounds and compositions comprising them (page 52, lines 5-7).
Conclusions
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Paul Arcoria whose telephone number is (571)272-8719. The examiner can normally be reached Mon-Fri 8:00-5:00 EST.
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/P.A./Examiner, Art Unit 1621
/CLINTON A BROOKS/Supervisory Patent Examiner, Art Unit 1621
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