Prosecution Insights
Last updated: April 19, 2026
Application No. 18/256,092

COMPOUNDS FOR INHIBITING INOSITOL HEXAKISPHOSPHATE KINASE (IP6K) AND METHODS OF USE THEREOF

Non-Final OA §102§103§112
Filed
Jun 06, 2023
Examiner
MOU, LIYUAN
Art Unit
1628
Tech Center
1600 — Biotechnology & Organic Chemistry
Assignee
Lieber Institute Inc.
OA Round
1 (Non-Final)
43%
Grant Probability
Moderate
1-2
OA Rounds
2y 11m
To Grant
99%
With Interview

Examiner Intelligence

Grants 43% of resolved cases
43%
Career Allow Rate
46 granted / 106 resolved
-16.6% vs TC avg
Strong +58% interview lift
Without
With
+58.3%
Interview Lift
resolved cases with interview
Typical timeline
2y 11m
Avg Prosecution
65 currently pending
Career history
171
Total Applications
across all art units

Statute-Specific Performance

§101
1.6%
-38.4% vs TC avg
§103
36.0%
-4.0% vs TC avg
§102
14.0%
-26.0% vs TC avg
§112
23.5%
-16.5% vs TC avg
Black line = Tech Center average estimate • Based on career data from 106 resolved cases

Office Action

§102 §103 §112
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 . DETAILED ACTION This office action is response to communication filed on 01/08/2026. Election/Restriction Applicant elected without traverse, Group I invention and compound species, PNG media_image1.png 20 553 media_image1.png Greyscale having structure shown below, on 01/08/2026. PNG media_image2.png 188 200 media_image2.png Greyscale The elected species is a compound of formula IA PNG media_image3.png 146 220 media_image3.png Greyscale PNG media_image4.png 146 353 media_image4.png Greyscale Claims 1-7 read on the elected invention and species. Claims 8-10, 12-13 and 16-23 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention. The elected species, Example 16 of instant disclosure(See PGPUB US 20250197396 A1) (CAS# 2762762-17-2 , entered STN database on March 21, 2022, See STN search note), is free of 102 anticipatory prior art. The Examiner has expanded search/examination to non-elected species wherein R1a and R2a is H or alkyl, R3a is H, La is CH2 or -C(=O)-, R4a is unsubstituted or substituted aryl(phenyl) or heteroaryl, which are rejected under following 102 and 103 rejection. Other non-elected species recited in claim are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to non-elected species, there being no allowable generic or linking claim. It should be noted that the prior art search will not be extended unnecessarily to cover all non-elected species. Should Applicant overcome the rejection by amending the claim, the amended claim will be reconsidered. The prior art search will be extended to the extent necessary to determine patentability of the Markush-type claim. In the event prior art is found during reconsideration that renders obvious or anticipates the amended Markush-type claim, the claim will be rejected and the action made final. Status of Claims Claims 1-10 , 12-13 and 16-23 are pending in the instant application. Claim 8-10, 12-13 and 16-23 are withdrawn. Claims 1-7 are under examination in this office action. Priority The instant application 18/256,092 filed on 06/06/2023, is a 371 of PCT/US21/62169 filed on 12/07/2021, which claims priority benefit of US provisional application No. 63/122,197 filed on 12/07/2020. Information Disclosure Statement The information disclosure statement dated 07/23/2024 is in compliance with the provisions of 37 CFR 1.97. The reference listed in IDS are being considered by the Examiner. Abstract The abstract of the disclosure is objected to because the abstract is less than 50 words in length , does not provide a general structure of instant claimed compounds and disease/disorders associated with IP6K activity thereof. Applicant is reminded of the proper content of an abstract of the disclosure. In chemical patent abstracts for compounds or compositions, the general nature of the compound or composition should be given as well as its use, e.g., “The compounds are of the class of alkyl benzene sulfonyl ureas, useful as oral anti-diabetics.” Exemplification of a species could be illustrative of members of the class. The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b). Specification The disclosure is objected to because CROSS-REFERENCES TO RELATED APPLICATIONS is missing. See 37 CFR 1.78 and MPEP § 211. 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. Claims 1-4 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. Claim 1 recites R4a is unsubstituted branched or straight chain C1-C4 alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloheteroalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl. There is no definition of substituents for the substituted C1-C4 alkyl, cycloalkyl, cycloheteroalkyl, aryl or heteroaryl. An ordinary skilled in the art would not be appraised the scope of compound of formula (IA). Thus, claim 1 is indefinite since the limitation of substituents do not clearly set forth the metes and bounds of the patent protection desired. Claims 2-4 are rejected due to dependency on 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. Claims 1-5 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by compounds having following structures, documented in CA Registry Database. PNG media_image5.png 607 584 media_image5.png Greyscale Compound (CAS# 2244338-38-1) is a compound of formula IA, wherein R1a is Me, R2a and R3a is H; La is CH2; R4a is unsubstituted aryl(phenyl). Thus, compound (CAS# 2244338-38-1) anticipates instant claimed invention. PNG media_image6.png 238 707 media_image6.png Greyscale PNG media_image7.png 218 339 media_image7.png Greyscale Compound (CAS#2244362-85-2) is a compound of Formula IA, wherein R1a is Me, R2a and R3a is H; La is CH2; R4a is unsubstituted heteroaryl(pyridinyl). Thus, compound (CAS# 2244362-85-2) anticipate instant claimed invention. PNG media_image8.png 249 712 media_image8.png Greyscale PNG media_image9.png 194 311 media_image9.png Greyscale Compound (CAS#2246366-76-3) is a compound of Formula IA, wherein R1a is Me, R2a is H, R3a is H; La is C(=O)-; R4a is unsubstituted cycloalkyl. Thus, compound (CAS# 2246366-76-3) anticipate instant claimed invention. 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 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 1-7 are rejected under 35 U.S.C. 103 as being unpatentable over Terao (WO2018182051A, Applicant’s IDS dated 07/23/2024), in view of Patani et al.(Chemical Reviews, 1996. Vol. 96, 8: 3147-3176, Bioisosterism: A Rational Approach in Drug Design). Terao teaches heterocyclic compound of Formula I as Inositol hexakisphosphate kinase (IP6K) inhibitors and method of prophylaxis or treatment of a disease associated with IP6K, e.g. cardiac failure and diabetes, etc. (See abstract, page 4,[0007]-[0008], Examples 1- 102; Table 5-1 to Table 5-24; claims 1-18). PNG media_image10.png 195 223 media_image10.png Greyscale PNG media_image11.png 484 711 media_image11.png Greyscale . Terao teaches compound species (e.g. compound 1, 9, 11, 12, etc. See Table 5-1, 5-2, etc.) that are similar to instantly claimed compound of Formula IA, wherein R1a, R2a and R3a is H, R4a is substituted or unsubstituted aryl and heteroaryl . PNG media_image12.png 137 588 media_image12.png Greyscale PNG media_image13.png 166 567 media_image13.png Greyscale PNG media_image14.png 141 585 media_image14.png Greyscale PNG media_image15.png 179 584 media_image15.png Greyscale The main difference of Terao compound with instant compound is the PNG media_image16.png 85 43 media_image16.png Greyscale moiety, wherein cyclohexane ring is different from instant piperidinyl ring (CH2 vs NH) and O is different from CH2 as La. Patani teaches CH2, NH, O are classic bioisosteres based on Grimm’s Hydride Displacement Law and Erlenmeyer’s definition of isosteres, which is within general knowledge of SAR study to a skilled artisan. Patani et al. teaches bioisosterism represents one approach used by the medicinal chemist for the rational modification of lead compounds. Patani et al. teaches a group of bioisosteres elicit similar biological activity, and have been classified as either classical or nonclassical, wherein the classical bioisosteres are a series of replacements defined by Grimm’s Hydride Displacement Law and Erlenmeyer’s definition of isosteres (See p. 3148-3149). PNG media_image17.png 106 404 media_image17.png Greyscale Terao’ teachings that X is CH and N, pyridine and phenyl ring as A moiety also illustrate bioisosteric replacement between CH and N. According to M.P.E.P. § 2144.09, a prima facie case of obviousness may be made when chemical compounds have very close structural similarities and similar utilities. "An obviousness rejection based on similarity in chemical structure and function entails the motivation of one skilled in the art to make a claimed compound, in the expectation that compounds similar in structure will have similar properties." In re Payne, 606 F.2d 303, 313, 203 USPQ 245, 254 (CCPA 1979). It would have been prima facie obvious to one of ordinary skilled in the art before the effective filing date of instant application to explore more IP6K inhibitors based on combined teachings of Terao, together with experimentation/optimization based on general knowledge of structure similarity and bioisosteric modification for SAR study as taught by Patani. As stated in MPEP § 2144.08 II subsection II. A. 4.(c), "Structural relationships may provide the requisite motivation or suggestion to modify known compounds to obtain new compounds". A skilled artisan would be motivated to explore/modify Terao compound based on structure similarity and bioisosteric modification as taught by Patani and reasonably expect the bioisosteric replacement/modification would provide more compounds that exhibit IP6K inhibitory activities. For example, compound 1 of Terao could be modified by replacing CH2 with N (cyclohexane to piperidine), and O with -CH2 and arrive at instant elected species. PNG media_image18.png 304 627 media_image18.png Greyscale One of ordinary skill in the art would have had reasonable expectation of success in producing the claimed invention base on the combined teachings of prior art and further exploration/optimization based on general knowledge of structure similarity and bioisosteric modification for SAR study of IP6K inhibitors . Therefore, the invention as a whole is prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, as evidenced by the references, especially in the absence of evidence to the contrary. Claims 1-6 are rejected under 35 U.S.C. 103 as being unpatentable over Claremon et al. (US20110136821A1). Claremon discloses spiro compound of Formula I and II, pharmaceutically acceptable salts thereof, as inhibitors 11 β-hydroxy steroid dehydrogenase type 1 (11β-HSDl), pharmaceutical compositions thereof and method of treating disease/disorder associated with 11β-HSDl, e.g. metabolic syndrome, diabetes, etc. (See abstract, [0014],[0036]-[0056], [0063]-[0104], Examples 1-106, [0465]-0466], claims 1, 11, 14-15, 30, 33). PNG media_image19.png 190 385 media_image19.png Greyscale PNG media_image20.png 42 464 media_image20.png Greyscale PNG media_image21.png 62 438 media_image21.png Greyscale PNG media_image22.png 76 450 media_image22.png Greyscale PNG media_image23.png 94 449 media_image23.png Greyscale PNG media_image24.png 222 514 media_image24.png Greyscale Claremon teaches compound species (e.g. compound 33, 67, 76, 78 etc.) that are similar to instantly claimed compound of Formula IA. PNG media_image25.png 76 394 media_image25.png Greyscale PNG media_image26.png 147 245 media_image26.png Greyscale PNG media_image27.png 224 394 media_image27.png Greyscale Example 78 of Claremon is similar to instantly compound of Formula IA, wherein R1a is C1-C4 alkyl, R2a is C1-C4 alkyl, R3a is H, La is C(=O)-(CH2)m, R4a is substituted phenyl. The difference of Example 78 and instant compound of Formula IA is La (CH2)m . Claremon teaches Q could be CH2 (m is 1). According to M.P.E.P. § 2144.09, a prima facie case of obviousness may be made when chemical compounds have very close structural similarities and similar utilities. "An obviousness rejection based on similarity in chemical structure and function entails the motivation of one skilled in the art to make a claimed compound, in the expectation that compounds similar in structure will have similar properties." In re Payne, 606 F.2d 303, 313, 203 USPQ 245, 254 (CCPA 1979). It would have been prima facie obvious to one of ordinary skilled in the art before the effective filing date of instant application to explore more inhibitors based on combined teachings of Claremon, together with experimentation/optimization based on general knowledge of structure similarity and bioisosteric modification for SAR study. As stated in MPEP § 2144.08 II subsection II. A. 4.(c), "Structural relationships may provide the requisite motivation or suggestion to modify known compounds to obtain new compounds". A skilled artisan would be motivated to explore/modify 11β-HSDl compound taught by Claremon based on structure similarity and bioisosteric modification and reasonably expect the bioisosteric replacement/modification would provide more compounds that might exhibit 11β-HSDl inhibitory activities. Therefore, the invention as a whole is prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, as evidenced by the references, especially in the absence of evidence to the contrary. Conclusion No claims are allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to LIYUAN MOU whose telephone number is (571)270-1791. The examiner can normally be reached Mon-Fri 9:00-5:30. Examiner interviews are available via telephone, in-person, and video using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Amy L Clark can be reached on (571)272-1310. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /LIYUAN MOU/Examiner, Art Unit 1628 /JARED BARSKY/Primary Examiner, Art Unit 1628
Read full office action

Prosecution Timeline

Jun 06, 2023
Application Filed
Mar 11, 2026
Non-Final Rejection — §102, §103, §112 (current)

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Study what changed to get past this examiner. Based on 5 most recent grants.

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Prosecution Projections

1-2
Expected OA Rounds
43%
Grant Probability
99%
With Interview (+58.3%)
2y 11m
Median Time to Grant
Low
PTA Risk
Based on 106 resolved cases by this examiner. Grant probability derived from career allow rate.

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