Prosecution Insights
Last updated: April 19, 2026
Application No. 18/072,314

HETEROCYCLIC COMPOUNDS AND USES THEREOF

Non-Final OA §DP
Filed
Nov 30, 2022
Examiner
WHITE, DAWANNA SHAR-DAY
Art Unit
1627
Tech Center
1600 — Biotechnology & Organic Chemistry
Assignee
Twelve Therapeutics, Inc.
OA Round
2 (Non-Final)
61%
Grant Probability
Moderate
2-3
OA Rounds
3y 9m
To Grant
92%
With Interview

Examiner Intelligence

Grants 61% of resolved cases
61%
Career Allow Rate
62 granted / 102 resolved
+0.8% vs TC avg
Strong +31% interview lift
Without
With
+30.8%
Interview Lift
resolved cases with interview
Typical timeline
3y 9m
Avg Prosecution
44 currently pending
Career history
146
Total Applications
across all art units

Statute-Specific Performance

§101
2.7%
-37.3% vs TC avg
§103
34.0%
-6.0% vs TC avg
§102
13.6%
-26.4% vs TC avg
§112
21.6%
-18.4% vs TC avg
Black line = Tech Center average estimate • Based on career data from 102 resolved cases

Office Action

§DP
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 . All previous objections and rejections not reiterated herein were overcome by claim amendments and arguments, filed January 21st, 2026, have been fully considered and found persuasive. As such all objections and rejections not reiterated herein have been withdrawn. Claim Objections Claims 172 and 173 are 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. Double Patenting The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969). A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b). The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13. The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer. Claims 170, 174 – 179, and 181 – 185 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 4, 6, 17, 24, 26 – 27, and 29 of U.S. Patent No. US 9775844 B2 to Kutok et. al. (herein after Kutok’844). Kutok’844 recite a method of treating a PI3K-gamma mediated disorder in a subject, comprising administering to the subject a therapeutically effective amount of a compound of the formula: PNG media_image1.png 200 400 media_image1.png Greyscale (instant claims 170 and 179) or a pharmaceutically acceptable salt thereof (reference claim 1). Furthermore, Kutok’844 recite a method wherein the subject has a PI3K-gamma mediated disorder selected from cancer, an inflammatory disease, or an autoimmune disease (reference claim 2); wherein the disorder is cancer and the cancer is a solid tumor (reference claim 3); wherein the disorder is a cancer selected from one or more of: a cancer of the pulmonary system, a brain cancer, a cancer of the gastrointestinal tract, a skin cancer, a genitourinary cancer (instant claim 179), head and neck cancer, a sarcoma, a carcinoma, and a neuroendocrine cancer (reference claim 4); wherein the disorder is a cancer selected from one or more of: a medullobastoma, a basal cell carcinoma, a glioma, a hepatocellular cancer, a gastrointestinal stromal tumor (GIST), a melanoma, a neuroectodermal tumor, a soft-tissue sarcoma, fibrosarcoma, myxosarcoma, liposarcoma, a chondrosarcoma, an osteogenic sarcoma, a chordoma, an angiosarcoma, an endotheliosarcoma, a lymphangiosarcoma, a lymphangioendotheliosarcoma, a synovioma, a mesothelioma, a leiomyosarcoma, a bladder carcinoma, an epithelial carcinoma, a squamous cell carcinoma, an adenocarcinoma, a bronchogenic carcinoma, a renal cell carcinoma, a hepatoma, a bile duct carcinoma, a carcinoid tumor, diffuse type giant cell tumor, and glioblastoma (reference claim 17). Furthermore, Kutok’844 recite a method wherein the therapeutically effective amount of the compound is about 2 mg per day, about 1 -3 mg per day, about 1 -5 mg per day, about 1-10 mg per day, about 0.5-20 mg per day, about 0.1-50 mg per day (instant claim 176 – 178 and 183 – 185), about 0.1-75 mg per day, about 0. 1 - 1 00 mg per day, about 0.1-250 mg per day, about 0.1 -500 mg per day, about 0.1-1000 mg per day, about 1 -50 mg per day, about 1-75 mg per day, about 1-100 mg per day, about 1 -250 mg per day, about 1 -500 mg per day, about 1 - 1000 mg per day, about 10-50 mg per day, about 10-75 mg per day, about 10-100 mg per day, about 10-250 mg per day, about 10-500 mg per day, about 10-1000 mg per day, about 100-500 mg per day, or about 100-1000 mg per day (reference claim 6); which further comprises administering an immunomodulator to the subject (reference claim 24); wherein the immunomodulator is a PDL-1 inhibitor or an anti-PDL-1 antibody (reference claim 26); wherein the PD-L1 inhibitor or the anti-PDL-1 antibody is YW243.55.S70, MDPL3280A, MSB0010718C, MDX-1105, or MEDI-4736 (reference claim 27); wherein the immunomodulator is a PD-1 inhibitor or an anti-PD-1 antibody (reference claim 28; instant claims 170 and 179); and wherein the PD-1 inhibitor or the anti-PD-1 antibody is nivolumab (reference claim 30; instant claims 175 and 182), pembrolizumab (reference claim 31; instant claims 174 and 181), pidilizumab, AMP-244, or AMP-5 14 (reference claim 29). While the instant application recites a method of treating head and neck squamous cell carcinoma, that is a species of squamous cell carcinoma; the conflicting invention of Kutok’844 recites a method of treating a PI3K-gamma mediated disorder wherein the disorder squamous cell carcinoma, a broad genus, or head and neck cancer, that is another broad genus. The instant recitation of for a method of treating head and neck squamous cell carcinoma is both a species of squamous cell carcinoma and head and neck cancer. Furthermore, both the instant application and the invention of Kutok’844 recite the administration of PNG media_image1.png 200 400 media_image1.png Greyscale in the conflicting methods as active steps. Furthermore, given the advanced skill level for one of ordinary skill in the pharmaceutical arts it would have been obvious to such artisan that the broad genus recitation of squamous cell carcinoma and head and neck cancer includes the species head and neck squamous cell carcinoma. Discussion of the Prior Art Claims 170, 172 – 179, and 181 – 185 are direct to a method of treating head and neck cancer in a subject, comprising administering to the subject a therapeutically effective amount of a compound of the formula: PNG media_image1.png 200 400 media_image1.png Greyscale or a pharmaceutically acceptable salt thereof, in combination with an anti-PD-1 antibody. The closet prior art of International Publication Number US 2013/0267521 A1 to Castro et. al. (herein after Castro’521; cited on the IDS dated April 28th, 2023) teach compounds capable of selectively inhibiting one or more isoform(s) of class I PI3K without substantially affecting the activity of the remaining isoforms of the same class (page 1 paragraph 0010). Specifically, Castro’521 teach compounds of Formula (I) PNG media_image2.png 168 174 media_image2.png Greyscale (page 23 paragraph 0221). More specifically, Castro’521 teach compound 154 of structure PNG media_image3.png 244 226 media_image3.png Greyscale (page 160 paragraph 0922). Castro’521 teach that a patient can be treat with compounds of the disclosure, including compounds of reference formula (I), for the treatment of head and neck cancer (claim 170), squamous cell carcinoma, and renal cancer (page 90 paragraph 0632). However, Castro’521 fails to teach a method wherein a compound of the formula: PNG media_image1.png 200 400 media_image1.png Greyscale is administered in combination with an anti-PD-1 antibody. Moreover, neither Castro’521 nor the prior art provides a motivation for modifying prior art compound 154 to get the instant compound of structure PNG media_image1.png 200 400 media_image1.png Greyscale . Given that the prior art of Castro’521 fails to anticipate or render obvious the method of the instant claims; instant claims 170 – 189 are free of the prior art. Conclusion Claims 170, 174 – 179, and 181 – 185 are rejected. Claims 172 – 173 are objected. Any inquiry concerning this communication or earlier communications from the examiner should be directed to DAWANNA S WHITE whose telephone number is (703)756-4687. The examiner can normally be reached 7:00 am - 5:00 pm [EST] M - Th. Examiner interviews are available via telephone, in-person, and video conferencing 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, 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. 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. /DAWANNA SHAR-DAY WHITE/Examiner, Art Unit 1627
Read full office action

Prosecution Timeline

Nov 30, 2022
Application Filed
Oct 17, 2025
Non-Final Rejection — §DP
Jan 21, 2026
Response Filed
Mar 02, 2026
Non-Final Rejection — §DP (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

2-3
Expected OA Rounds
61%
Grant Probability
92%
With Interview (+30.8%)
3y 9m
Median Time to Grant
Moderate
PTA Risk
Based on 102 resolved cases by this examiner. Grant probability derived from career allow rate.

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