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 in response to the application 18/696,946 filed on 28 March 2024, 371 of PCT/US22/26623 filed on 28 April 2022, with PRO 63/277,309 filed on 09 November 2021 and PRO 63/181,625 filed on 29 April 2021. Claims 6-8, 11, 14, 20, 22, 24, 27, 29, 33, 35-37, 39 and 50 are amended. Claims 16-19, 21, 28, 34, 40-46 and 54 are canceled. Currently, claims 1-15, 20, 22-27, 29-33, 35-39, 47 and 50-53 are pending.
Information Disclosure Statement
The information disclosure statements (IDSs) submitted on 04 April 2025, 12 September 2025, 03 October 2025, 01 April 2026, 07 April 2026, and 23 July 2026 were filed after the mailing date of the application on 28 March 2024. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Election/Restrictions
Applicant’s election of Group I without traverse in the response filed on 23 July 2026 is acknowledged.
Applicant’s election of the compound 4-(4-((1R, 5S)-3,8-diazabicyclo[3.2.1]octan-3-yl)-2-(((2R,7aS)-2-fluorotetrahydro-1H,pyrrolizin-7a(5H)-yl)methoxy)quinazolin-7-yl)-5-ethyl-6-fluoronaphthalen-2-ol, illustrated below, in the response filed on 23 July 2026 is acknowledged.
PNG
media_image1.png
156
209
media_image1.png
Greyscale
Applicant’s election of non-small cell lung cancer in the response filed on 23 July 2026 is acknowledged.
The elected species, per Applicant’s remarks, reads upon claims 1-2, 5-10, 20, 22-27, 29-30, 32-33 and 35-39. As such, claims 3-4, 11-15, 31, 47 and 50-53 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected invention or species, there being no allowable generic or linking claim. Election was made in the reply filed on 23 July 2026.
The elected species was found to be free of the prior art.
The closest matches are Tian et al. (Heterocyclic compounds as Kras inhibitor, and preparation therefor and use thereof in treatment, US 2024/0300980 A1, 2024) who discloses the elected compound as compound 92 for the purpose of treating HRas, KRas and NRas, illustrated below (pg. 71):
PNG
media_image2.png
164
171
media_image2.png
Greyscale
However, the prior art is after the claimed priority date of the instant application.
Wang et al. (KRAS G12D Inhibitors, WO 2021/041671 A1, 2021; entered into the IDS on 04 April 2025) discloses the compound below for the purpose of treating KRas, which nearly reads on the elected species except for the inclusion of an additional nitrogen in the heterocyclic core, illustrated below (pg. 37):
PNG
media_image3.png
166
226
media_image3.png
Greyscale
Malhotra et al. (Fused ring compounds, WO 2020/097537 A2, 2020) discloses compounds with similar structures for the treatment of Ras proteins including KRas, HRas, and NRas, including a heterocyclic core that reads upon the instant application, an example being compound 67a, illustrated below (pg. 61):
PNG
media_image4.png
186
229
media_image4.png
Greyscale
The search was expanded to the elected scope of the claims.
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 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 non-obviousness.
Claims 1-2, 5-10, 20, 22-27, 29-30, 32-33, 35-37, and 39 are rejected under 35 U.S.C. 103 as being unpatentable over Wang et al. (KRAS G12D Inhibitors, WO 2021/041671 A1, 2021; entered into the IDS on 04 April 2025) in view of Malhotra et al. (Fused ring compounds, WO 2020/097537 A2, 2020).
Wang discloses several compounds for the purpose of inhibiting KRas, including the structure illustrated below, that nearly reads upon the elected species except for the inclusion of an additional nitrogen in the heterocyclic core (pg. 37):
PNG
media_image3.png
166
226
media_image3.png
Greyscale
They do not, however, teach where the core heterocyclic structure does not have the inclusion of a nitrogen on the pyridyl ring.
Malhotra rectifies this deficiency by teaching compounds also purposed for inhibiting Ras proteins including compounds such as compound 67a, illustrated below (pg. 61):
PNG
media_image4.png
186
229
media_image4.png
Greyscale
As such, it would be prima facie obvious, to a person of ordinary skill in the art, before the effective filing date, to consider incorporating the heterocyclic core structure of Malhotra into the structures of Wang as both maintain the planar sp2 aromatic geometry of the core structure while being demonstratively applicable toward Ras inhibition.
Regarding the limitations of claim 2, these are met as the exemplary compound from Wang does not include R3 = benzo[d]thiazole.
Concerning the limitations of claim 5, these are met as the exemplary compound from Wang has Z = N.
Pertaining to the limitations of claim 6, these are met as the exemplary compound from Wang has W = N.
With respect to the limitations of claim 7, these are met as the exemplary compound from Wang has n = 1.
With regards to the limitations of claim 8, these are met as the exemplary compound from Wang has m = 2.
With concern to the limitations of claim 9, these are met as the exemplary compound from Wang has the two Rx form a C2-alkylene bridged ring.
Regarding the limitations of claim 10, these are met as the exemplary compound from Wang has the two Rx form an ethylene bridged ring.
Concerning the limitations of claim 20, these are met as the exemplary compound from Wang has the structural limitations being
PNG
media_image5.png
80
43
media_image5.png
Greyscale
.
Pertaining to the limitations of claim 22, these are met as the exemplary compound from Wang has L = -O-C1 alkylene.
With respect to the limitations of claim 23, these are met as the exemplary compound from Wang has L = -O-methylene-.
With regards to the limitations of claim 24, these are met as the exemplary compound from Wang has R1 = a heterocycloalkyl with one occurrence of R5.
With concern to the limitations of claim 25, these are met as the exemplary compound from Wang has R1 = 7-(hexahydro-1H-pyrrolizine).
Regarding the limitations of claim 26, these are met as the exemplary compound from Wang has R5 = halogen.
Concerning the limitations of claim 27, these are met as the exemplary compound from Wang has -L-R1 =
PNG
media_image6.png
78
95
media_image6.png
Greyscale
.
Pertaining to the limitations of claim 29, these are met as the exemplary compound from Wang has R3 = naphthyl substituted with 3 occurrences of R6.
With respect to the limitations of claim 30, these are met as the exemplary compound from Wang has R3 = naphthyl substituted with 3 occurrences of R6.
With regards to the limitations of claim 32, these are met as the exemplary compound from Wang has R6 = fluorine, ethyl and hydroxyl.
With concern to the limitations of claim 33, these are met as the exemplary compound from Wang has R3 =
PNG
media_image7.png
122
77
media_image7.png
Greyscale
.
Regarding the limitations of claim 35, these are met as the exemplary compound from Malhotra has R2 = chlorine.
Concerning the limitations of claim 36, these are met as the exemplary compound from Wang has R4 = fluorine.
Pertaining to the limitations of claim 37, these are met as the exemplary compound from Wang has R7 = hydrogen.
With respect to the limitations of claim 39, these are met as Wang teaches pharmaceutical compositions for KRas G12D inhibitors including administration, salts, and carriers (para. 0169-0175).
Allowable Subject Matter
Claim 38 is 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.
Reasons For Allowable Subject Matter
The following is a statement of reasons for the indication of allowable subject matter: the elected species was not found in the prior art in a 100% embodiment. The prior art does not read upon the species listed in the claim. The closest prior are Tian et al. (Heterocyclic compounds as Kras inhibitor, and preparation therefor and use thereof in treatment, US 2024/0300980 A1, 2024) who discloses the elected compound as compound 92 for the purpose of treating HRas, KRas and NRas, illustrated below (pg. 71):
PNG
media_image2.png
164
171
media_image2.png
Greyscale
However, the prior art is after the claimed priority date of the instant application.
Wang et al. (KRAS G12D Inhibitors, WO 2021/041671 A1, 2021; entered into the IDS on 04 April 2025) discloses the compound below for the purpose of treating KRas, which nearly reads on the elected species except for the inclusion of an additional nitrogen in the heterocyclic core, illustrated below (pg. 37):
PNG
media_image3.png
166
226
media_image3.png
Greyscale
Malhotra et al. (Fused ring compounds, WO 2020/097537 A2, 2020) discloses compounds with similar structures for the treatment of Ras proteins including KRas, HRas, and NRas, including a heterocyclic core that reads upon the instant application, an example being compound 67a, illustrated below (pg. 61):
PNG
media_image4.png
186
229
media_image4.png
Greyscale
Double Patenting
The non-statutory 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 non-statutory 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 non-statutory 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 non-statutory 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.
Claim 1 is provisionally rejected on the ground of non-statutory double patenting as being unpatentable over claim 1 of co-pending Application No. 18/695,688 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the general structure as described by formula (I) in the ‘688 application broadly reads into formula (I) of the instant application.
This is a provisional non-statutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 1 is provisionally rejected on the ground of non-statutory double patenting as being unpatentable over claim 1 of co-pending Application No. 18/696,948 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the general structure as described by formula (I) in the ‘948 application reads into formula (I) of the instant application where R3 is heteroaryl.
This is a provisional non-statutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 1 is provisionally rejected on the ground of non-statutory double patenting as being unpatentable over claim 1 of co-pending Application No. 18/695,693 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the general structure of formula (I) of the ‘693 application largely reads upon formula (I) of the instant application, contrasting with the inclusion of a nitrogen in the bicyclic core. However, this inclusion maintains the sp2 geometry of the structure and therefore does not readily make apparent the significance of such an inclusion.
This is a provisional non-statutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Summary
Claims 1-2, 5-10, 20, 22-27, 29-30, 32-33, 35-37 and 39 are rejected under 35 U.S.C. 103. Claim 38 is objected to as being dependent on a rejected base claim. Claim 1 is rejected under non-statutory double patenting. Claims 3-4, 11-15, 31, 47 and 50-53 are withdrawn.
Conclusion
Claims 1-2, 5-10, 20, 22-27, 29-30, 32-33, 35-37 and 39 are rejected. Claim 38 is objected to. Claims 3-4, 11-15, 31, 47 and 50-53 are withdrawn.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Allen Chao whose telephone number is (571)272-7001. The examiner can normally be reached Monday - Friday 0700-1300.
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.
/ALLEN CHAO/Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622
Prosecution Insights