Prosecution Insights
Last updated: April 19, 2026
Application No. 19/281,019

SYNTHESIS OF KEY INTERMEDIATE OF KRAS G12C INHIBITOR COMPOUND

Non-Final OA §DP
Filed
Jul 25, 2025
Examiner
SIMMONS, CHRIS E
Art Unit
1622
Tech Center
1600 — Biotechnology & Organic Chemistry
Assignee
Amgen, Inc.
OA Round
1 (Non-Final)
34%
Grant Probability
At Risk
1-2
OA Rounds
3y 10m
To Grant
53%
With Interview

Examiner Intelligence

Grants only 34% of cases
34%
Career Allow Rate
229 granted / 665 resolved
-25.6% vs TC avg
Strong +19% interview lift
Without
With
+18.9%
Interview Lift
resolved cases with interview
Typical timeline
3y 10m
Avg Prosecution
45 currently pending
Career history
710
Total Applications
across all art units

Statute-Specific Performance

§101
1.0%
-39.0% vs TC avg
§103
46.2%
+6.2% vs TC avg
§102
14.3%
-25.7% vs TC avg
§112
23.8%
-16.2% vs TC avg
Black line = Tech Center average estimate • Based on career data from 665 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 . Priority This application claims the benefit of U.S. Provisional Patent Application No. 63/088,848, filed October 7, 2020, and U.S. Provisional Patent Application No. 63/162,278, filed March 17, 2021. Information Disclosure Statement The Information Disclosure Statements filed 7/25/2025 have been considered by the Examiner. The submissions are in compliance with the provisions of 37 CFR §§ 1.97 and 1.98. Enclosed with this Office Action is a return-copy of the Forms PTO-1449 with the Examiner’s signature and indication of those references that have been considered. 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. A. Claim 1 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 15, 16, 19, 21 and 22 of U.S. Patent No. 12,441,729 in view of Chenard et al. (US 6,323,208 B1). Claimed invention Claim 1 is drawn to a process of preparing a compound of Formula (5M) PNG media_image1.png 182 69 media_image1.png Greyscale comprising mixing compound of Formula 4 PNG media_image2.png 109 58 media_image2.png Greyscale with a chiral acid, and crystallizing the mixture of Formula (4) and the chiral acid to provide a cocrystal compound of Formula (5M) and the chiral acid. Patent/Reference claims The patent claims teach a process of preparing Compound A PNG media_image2.png 109 58 media_image2.png Greyscale (A) and using it to make Compound F PNG media_image3.png 304 330 media_image3.png Greyscale (F), a pharmaceutically acceptable salt, atropisomer, or a pharmaceutically acceptable salt of an atropisomer thereof. While the patent claims teach that atropisomer forms of Compound F PNG media_image3.png 304 330 media_image3.png Greyscale can be made from Compound A PNG media_image2.png 109 58 media_image2.png Greyscale , the patent claims do not teach mixing Compound A with a chiral acid and crystallizing the mixture of Compound A and the chiral acid to provide a cocrystal compound of Compound A and the chiral acid. However, the process of forming cocrystals by mixing a chiral acid such as tartaric acid with another compound in order to resolve atropisomers of the compounds was already known. For example, racemic mixtures of atropisomers that contain an acidic or basic moiety, chiral resolution may be achieved by forming diastereomeric salts with optically pure acids (for example, tartaric acid) when the racemate contains a basic moiety or with optically pure bases (for example a-methylbenzyl amine) when the racemate contains an acidic moiety. Repeated recrystallizations of these diastereomeric salts will allow the single pure atropisomer to be obtained. The single pure atropisomer can be used directly as a salt or may be neutralized to obtain the free base or free acid atropisomer. See Chenard, col. 13, third paragraph. A person of ordinary skill in the art (POSA) would have found it obvious to mix a chiral acid such as tartaric acid with Compound A PNG media_image2.png 109 58 media_image2.png Greyscale with repeated recrystallization to form the diastereomeric salt with an optically pure acid such as tartaric acid to form a cocrystal containing the salt and an atropisomer of Compound A including the M-atropisomer such as PNG media_image1.png 182 69 media_image1.png Greyscale because the patent claims teach that the final compound, Compound F can be made in the form of an atropisomer or a pharmaceutically acceptable salt of an atropisomer, and Chenard teaches that, in atropisomers that contain a basic moiety, chiral resolution may be achieved by forming diastereomeric salts with optically pure acids such as tartaric acid; and repeated recrystallizations of these salts allow the single pure atropisomer to be obtained. Chenard also teaches single pure atropisomer can be used directly as a salt or may be neutralized to obtain the free base or free acid atropisomer. The POSA would have had a reasonable expectation of success with preparing a cocrystal of a pharmaceutically acceptable salt of an atropisomer of Compound A and tartaric acid because Compound A has a basic moiety due to the presence of nitrogen in the ring and tartaric acid can be used for chiral resolution of atropisomers with a basic moiety to form cocrystals containing the atropisomer and salt. Therefore, the claimed invention as a whole would have been prima facie obvious at the time the invention application was filed. B. Claim 1 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 14-16 of U.S. Patent No. 12,473,281 in view of Chenard et al. (US 6,323,208 B1). Claimed invention Claim 1 is drawn to a process of preparing a compound of Formula (5M) PNG media_image1.png 182 69 media_image1.png Greyscale comprising mixing compound of Formula 4 PNG media_image2.png 109 58 media_image2.png Greyscale with a chiral acid, and crystallizing the mixture of Formula (4) and the chiral acid to provide a cocrystal compound of Formula (5M) and the chiral acid. Patent/Reference claims The patent claims teach a process that includes mixing Compound 4 PNG media_image4.png 226 190 media_image4.png Greyscale (4) with (+)-DBTA (i.e., a chiral acid) and arriving at Compound (4A) PNG media_image5.png 494 404 media_image5.png Greyscale (4A) (i.e., a salt containing the atropisomer of Compound 4) and, after additional steps, eventually arriving at Compound (5M), PNG media_image6.png 216 194 media_image6.png Greyscale (5M) (i.e., the atropisomer of Compound 4). While the patent claims teach mixing Compound 4 with (+)-DBTA (i.e., a chiral acid) to make Compound (4A) (i.e., a salt containing the atropisomer of Compound 4 and (+)-DBTA) and eventually make Compound (5M), PNG media_image6.png 216 194 media_image6.png Greyscale (i.e., the atropisomer of Compound 4), the patent claims do not teach crystallizing the mixture to provide a cocrystal compound of Compound 4A and the chiral acid. However, the process of forming cocrystals by mixing a chiral acid (e.g., tartaric acid) with another compound and recrystallizing the mixture in order to resolve atropisomers of the compounds was already known. For example, racemic mixtures of atropisomers that contain an acidic or basic moiety, chiral resolution may be achieved by forming diastereomeric salts with optically pure acids (for example, tartaric acid) when the racemate contains a basic moiety or with optically pure bases (for example a-methylbenzyl amine) when the racemate contains an acidic moiety. Repeated recrystallizations of these diastereomeric salts will allow the single pure atropisomer to be obtained. The single pure atropisomer can be used directly as a salt or may be neutralized to obtain the free base or free acid atropisomer. See Chenard, col. 13, third paragraph. A person of ordinary skill in the art (POSA) would have found it obvious to mix a chiral acid such as tartaric acid or (+)-DBTA with Compound 4 PNG media_image2.png 109 58 media_image2.png Greyscale with repeated recrystallization to form the diastereomeric salt with an optically pure acid (e.g., tartaric acid, (+)-DBTA) to form a cocrystal containing the acid and Compound 4A (i.e., atropisomer) because the patent claims teach Compound 4, which is not an atropisomer, is mixed with (+)-DBTA (i.e., a chiral acid) to make Compound 4A (i.e., an atropisomer salt) that can be used to make Compound 5M (an atropisomer), and Chenard teaches that, in atropisomers that contain a basic moiety, chiral resolution may be achieved by forming diastereomeric salts with optically pure acids such as a tartaric acid; and repeated recrystallizations of these salts allow the single pure atropisomer to be obtained. Chenard also teaches single pure atropisomer can be used directly as a salt or may be neutralized to obtain the free base or free acid atropisomer. The POSA would have had a reasonable expectation of success with preparing a cocrystal of a pharmaceutically acceptable salt of Compound 4A and chiral acid (e.g., tartaric acid, (+)-DBTA) because Compound 4 has a basic moiety due to the presence of nitrogen in the ring and the chiral acid - tartaric acid for example - can be used for chiral resolution of atropisomers with a basic moiety to form cocrystals containing the atropisomer and salt. Therefore, the claimed invention as a whole would have been prima facie obvious at the time the invention application was filed. C. Claim 1 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 11 and 12 of U.S. PG-PUB 2025/0122197 in view of Chenard et al. (US 6,323,208 B1). Claimed invention Claim 1 is drawn to a process of preparing a compound of Formula (5M) PNG media_image1.png 182 69 media_image1.png Greyscale comprising mixing compound of Formula 4 PNG media_image2.png 109 58 media_image2.png Greyscale with a chiral acid, and crystallizing the mixture of Formula (4) and the chiral acid to provide a cocrystal compound of Formula (5M) and the chiral acid. Patent/Reference claims The patent claims teach a process of preparing a racemized Compound A PNG media_image2.png 109 58 media_image2.png Greyscale which is resolved using tartrate (chiral acid) to separate it into its respective atropisomers, i.e., (P)-compound A and (M)-compound A (i.e., PNG media_image1.png 182 69 media_image1.png Greyscale ). While the patent claims teach that racemized Compound A can be mixed with tartrate to form its (P)- and (M)-atropisomers (e.g., PNG media_image1.png 182 69 media_image1.png Greyscale ), the patent claims do not teach crystallizing the mixture to provide a cocrystal compound of the (M)-atropisomer and the chiral acid. However, the process of forming cocrystals by mixing a chiral acid (e.g., tartaric acid) with another compound and recrystallizing the mixture in order to resolve atropisomers of the compounds was already known. For example, racemic mixtures of atropisomers that contain an acidic or basic moiety, chiral resolution may be achieved by forming diastereomeric salts with optically pure acids (for example, tartaric acid) when the racemate contains a basic moiety or with optically pure bases (for example a-methylbenzyl amine) when the racemate contains an acidic moiety. Repeated recrystallizations of these diastereomeric salts will allow the single pure atropisomer to be obtained. The single pure atropisomer can be used directly as a salt or may be neutralized to obtain the free base or free acid atropisomer. See Chenard, col. 13, third paragraph. A person of ordinary skill in the art (POSA) would have found it obvious to mix a chiral acid such as tartaric acid or (+)-DBTA with Compound 4 PNG media_image2.png 109 58 media_image2.png Greyscale with repeated recrystallization to form the diastereomeric salt with an optically pure acid (e.g., tartaric acid, (+)-DBTA) to form a cocrystal containing the acid and Compound 4A (i.e., atropisomer) because the patent claims teach Compound 4, which is not an atropisomer, is mixed with (+)-DBTA (i.e., a chiral acid) to make Compound 4A (i.e., an atropisomer salt) that can be used to make Compound 5M (an atropisomer), and Chenard teaches that, in atropisomers that contain a basic moiety, chiral resolution may be achieved by forming diastereomeric salts with optically pure acids such as a tartaric acid; and repeated recrystallizations of these salts allow the single pure atropisomer to be obtained. Chenard also teaches single pure atropisomer can be used directly as a salt or may be neutralized to obtain the free base or free acid atropisomer. The POSA would have had a reasonable expectation of success with preparing a cocrystal of a pharmaceutically acceptable salt of Compound 4A and chiral acid (e.g., tartaric acid, (+)-DBTA) because Compound 4 has a basic moiety due to the presence of nitrogen in the ring and the chiral acid - tartaric acid for example - can be used for chiral resolution of atropisomers with a basic moiety to form cocrystals containing the atropisomer and salt. Therefore, the claimed invention as a whole would have been prima facie obvious at the time the invention application was filed. This is a provisional rejection. D. Claim 1 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, and 21-23 of U.S. PG-PUB 2023/0391771 in view of Chenard et al. (US 6,323,208 B1). Claimed invention Claim 1 is drawn to a process of preparing a compound of Formula (5M) PNG media_image1.png 182 69 media_image1.png Greyscale comprising mixing compound of Formula 4 PNG media_image2.png 109 58 media_image2.png Greyscale with a chiral acid, and crystallizing the mixture of Formula (4) and the chiral acid to provide a cocrystal compound of Formula (5M) and the chiral acid. Patent/Reference claims The patent claims teach a process of preparing a racemized Compound A PNG media_image2.png 109 58 media_image2.png Greyscale which is resolved using tartrate (chiral acid) to separate it into its respective atropisomers, i.e., (P)-compound A and (M)-compound A (i.e., PNG media_image1.png 182 69 media_image1.png Greyscale ). While the patent claims teach that racemized Compound A can be mixed with tartrate to form its (P)- and (M)-atropisomers (e.g., PNG media_image1.png 182 69 media_image1.png Greyscale ), the patent claims do not teach crystallizing the mixture to provide a cocrystal compound of the (M)-atropisomer and the chiral acid. However, the process of forming cocrystals by mixing a chiral acid (e.g., tartaric acid) with another compound and recrystallizing the mixture in order to resolve atropisomers of the compounds was already known. For example, racemic mixtures of atropisomers that contain an acidic or basic moiety, chiral resolution may be achieved by forming diastereomeric salts with optically pure acids (for example, tartaric acid) when the racemate contains a basic moiety or with optically pure bases (for example a-methylbenzyl amine) when the racemate contains an acidic moiety. Repeated recrystallizations of these diastereomeric salts will allow the single pure atropisomer to be obtained. The single pure atropisomer can be used directly as a salt or may be neutralized to obtain the free base or free acid atropisomer. See Chenard, col. 13, third paragraph. A person of ordinary skill in the art (POSA) would have found it obvious to mix a chiral acid such as tartaric acid or (+)-DBTA with Compound 4 PNG media_image2.png 109 58 media_image2.png Greyscale with repeated recrystallization to form the diastereomeric salt with an optically pure acid (e.g., tartaric acid, (+)-DBTA) to form a cocrystal containing the acid and Compound 4A (i.e., atropisomer) because the patent claims teach Compound 4, which is not an atropisomer, is mixed with (+)-DBTA (i.e., a chiral acid) to make Compound 4A (i.e., an atropisomer salt) that can be used to make Compound 5M (an atropisomer), and Chenard teaches that, in atropisomers that contain a basic moiety, chiral resolution may be achieved by forming diastereomeric salts with optically pure acids such as a tartaric acid; and repeated recrystallizations of these salts allow the single pure atropisomer to be obtained. Chenard also teaches single pure atropisomer can be used directly as a salt or may be neutralized to obtain the free base or free acid atropisomer. The POSA would have had a reasonable expectation of success with preparing a cocrystal of a pharmaceutically acceptable salt of Compound 4A and chiral acid (e.g., tartaric acid, (+)-DBTA) because Compound 4 has a basic moiety due to the presence of nitrogen in the ring and the chiral acid - tartaric acid for example - can be used for chiral resolution of atropisomers with a basic moiety to form cocrystals containing the atropisomer and salt. Therefore, the claimed invention as a whole would have been prima facie obvious at the time the invention application was filed. This is a provisional rejection. Conclusion No claims are allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHRIS E SIMMONS whose telephone number is (571)272-9065. The examiner can normally be reached M-F: 9:30-6:00p. 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, James H. Alstrum-Acevedo can be reached at (571) 272-5548. 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. CHRIS E. SIMMONS Examiner Art Unit 1622 /CHRIS E SIMMONS/Examiner, Art Unit 1622 /JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622
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Prosecution Timeline

Jul 25, 2025
Application Filed
Dec 27, 2025
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

1-2
Expected OA Rounds
34%
Grant Probability
53%
With Interview (+18.9%)
3y 10m
Median Time to Grant
Low
PTA Risk
Based on 665 resolved cases by this examiner. Grant probability derived from career allow rate.

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