DETAILED ACTION
Claims 1-104 are pending.
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
The instant application filed 3/22/2024 is a National Stage entry of PCT/US2022/045623, with an International Filing Date of 10/4/2022. PCT/US2022/045623 claims Priority from Provisional Application 63252561, filed 10/5/2021.
Information Disclosure Statement
The Information Disclosure Statements (IDS) submitted on 5/10/2024 and 7/29/2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the Information Disclosure Statements are being considered by the Examiner.
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-90 and 93-101 in the Reply filed on 8/18/2026, is acknowledged.
Claims 91, 92, and 102-104 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the Reply.
Applicant’s election of species to MRTX1133 and TNO155 (Batoprotafib) is acknowledged, claims 1-9, 45, 49, 53, 57, 86-90, and 93-101 in the Reply filed on 8/18/2026, is acknowledged.
Claims 10-44, 46-48, 50-52, 54-56, 58-85 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the Reply.
Claims 1-9, 45, 49, 53, 57, 86-90, and 93-101 are present for Examination and the subject of the Office Action below.
The requirement is still deemed proper and is therefore made FINAL.
Background Information
PNG
media_image1.png
348
544
media_image1.png
Greyscale
Entered into CA Registry 3/29/2021 as 2621928-55-8.
PNG
media_image2.png
220
544
media_image2.png
Greyscale
TNO155
Claim Rejections - 35 USC § 112(b)
(Indefinite)
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.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-9, 45, 49, 53, 57, 86-90, and 93-101 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.
Applicant’s claim 1 states, “a KRAS G12D inhibitor of formula (I).” This recitation is indefinite as the claimed formula includes compounds that are not “a KRAS G12D inhibitor” as known in the art. For example, WO 2020146613 teaches 2454396-32-6 as a KRAS G12C inhibitor.
PNG
media_image3.png
528
772
media_image3.png
Greyscale
This prior art compound is anticipatory to the instantly claimed genus but is taught as a KRAS G12C inhibitor. This makes the claim indefinite as it is unclear what activity is produced by the compounds compared to the structures being claimed. The label and the structure do not match the Structure Activity Relationship, and Applicant has not required any activity, only structure. Therefore claiming “a KRAS G12D inhibitor of formula (I)” is indefinite.
Claim Rejections - 35 USC § 112(a)
(Written Description)
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 1-9, 45, 49, 53, 57, 86-90, and 93-101 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.
Applicant is claiming that “an extensive genus” of KRAS G12D inhibitors (including a known KRAS G12C inhibitor) in combination with any SHP-2 inhibitor will treat ALL cancers.
Applicant has shown only one combination, MRTX1133 and TNO155 (Batoprotafib), in two very specific cancer types, colorectal cancer with mutated KRAS G12D and pancreatic cancer with mutated KRAS G12D.
Applicant has not provided any other data points or teaching as to why this showing (1 combination in 2 cancers) would provide written description for the entire scope claimed. Clearly Applicant is teaching the KRAS inhibitor must be a selective G12D inhibitor of a specific structure, the SHP-2 inhibitor must be selective and a specific structure, and that the cancer must be a specific type with a KRAS G12D mutation that drives the growth. As such given the few examples provided by Applicant, given the fact that the art is not established in this field, Applicant has not described (shown possession) the entire scope instantly claimed.
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 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 1-6, 45, 53, 57, 86-90, and 93-101 are rejected under 35 U.S.C. 103 as being unpatentable over Henary et al. WO 2021076655 A1 published 4/22/2021 with priority to 10/15/2019; and Marx et al. WO 2020146613 A1 published 7/16/2020 with priority to 1/10/2019.
Instant claim 1 is directed to a method of treating cancer in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a combination of a SHP-2 inhibitor and a KRAS G12D inhibitor of formula (I).
A KRAS G12D inhibitor of formula (I) limitation is met by the KRAS G12C inhibitor of Marx. See 112(b) rejection above.
Henary teaches treating cancer with “AMG510” a KRAS G12C inhibitor in combination with SHP-2 inhibitors, including TNO155.
Marx teaches RN# 2454396-32-6 as a KRAS G12C inhibitor.
PNG
media_image3.png
528
772
media_image3.png
Greyscale
A person of ordinary skill in the art would find it obvious to substitute AMG510 with RN# 2454396-32-6, to arrive at the instantly claimed invention as the simple substitution of one known compound for another with the same activity would be expected to give the same predictable result of treating KRAS mutated cancer with a combination of KRAS mutant inhibitor and SHP-2 inhibitor. As such there is a prima facie case of obviousness.
Regarding instant claims 1-6, 45, 53, 57 directed to the structure of the SHP-2 inhibitor and the KRAS G12D inhibitor of formula (I) are met by the compounds taught in the art.
Regarding claims 86-89 and 95-98 are directed to timing of the administration, and to the dose (limitations taught by the instant references in generic form and taught to be optimized for efficacy). These claims are obvious as a doctor would optimize these variables to get the desired efficacy while minimizing toxicity. The dosing protocols are similar to those taught in Henary, and are obvious based on these limitations being directed to routine optimization of variables shown to have effects on efficacy and toxicity. See MPEP 2144.05, that discusses the ranges and routine optimization.
Instant claim 90 is simply a recitation of the result of treatment and does not lend to patentability. See MPEP 2111.04 I. The court noted that a "‘whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.’" Id. (quoting Minton v. Nat’l Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003)).
Instant claims 99-101 are directed to a specific cancer and to cancer that is KRAS G12D associated. Given the art teaches using the same compound for KRAS mutated cancer at the G12 in combination with a SHP-2 inhibitor, these claims are obvious unless Applicant can show a clearly defined definition of the inhibitor and the cancer the combination treats.
Conclusion
No claims allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MICHAEL J SCHMITT whose telephone number is (571)270-7047. The examiner can normally be reached M-F 8-6 MidDay Flex.
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, Jeffrey Lundgren can be reached at 571-272-5541. 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.
/MICHAEL J SCHMITT/Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/Supervisory Patent Examiner, Art Unit 1629
