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
Election/Restriction
In response to Restriction Requirement mailed on 03/25/2026, Applicant cancelled all claims 91-110, dated 02/20/2024 which lack unity in view of prior art Wang (WO2022/132200 A1) and add new claims 111-133 in the reply 05/15/2026. Applicant elected, with traverse, Compound ID # 51 having following structure,
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Applicant argues compounds recited in new claims shares common structure, and Wang does not disclose compound with a 1,4-oxazepane ring of
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. Please note Applicant cannot cancel all of the old claims that lack unity in view of the cited Wang reference and argues Wang does not break unity of new claims. Further, Wang teaches compound species comprising the core structure of instant compound and very similar to instant compounds except the fused 1, 4-oxazepane as elaborated in the following 35 USC 103 rejection. Instant claimed compounds is obvious in view of Wang, thus, the Restriction Requirement is proper and made Final.
It’s noted the numbering of compounds in instant specification is NOT consistent and confusing. The elected species is a compound ID# 51 in Table 18 (page 56), which is Compound 33 disclosed in Example 33 ( page 115 ) of instant specification, which has different structure from Compound 51 disclosed in Example 51(page 128) of instant specification.
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,
The elected species, Compound 33 is a compound of Formula recited in claim 111, wherein RS1 is halogen, z1 is 0, R4a is F, OH and
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. New claims 111-133 read on the elected species.
The elected species ( CAS# 2904559-44-8 ) and stereoisomers entered in STN database on March 06, 2023.
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After reasonable and comprehensive search, the elected species ( recited in instant claim 132) is rejected as being obvious over Wang (WO2022/132200 A1) and Yamano et al. ( WO2023018809 A1). Other non-elected species are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected species. It should be noted that 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 111-133 are pending and currently under examination.
Priority
This instant application 18/684, 205, filed February 16, 2024 , is a 371 of PCT/CN2022/112919 filed August 17, 2022, which claims the benefit of priority to PCT/CN2021/113365 filed on August 18, 2021; PCT/CN2021/123382, filed on October 12, 2021; PCT/CN2021/123604, filed on October 13, 2021; PCT/CN2021/123884, filed on October 14, 2021; PCT/CN2021/132070, filed on November 22, 2021; PCT/CN2021/137092, filed on December 10, 2021; PCT/CN2022/077678, filed on February 24, 2022; PCT/CN2022/081022, filed on March 15, 2022; PCT/CN2022/084321, filed on March 31, 2022; PCT/CN2022/084273, filed on March 31, 2022; PCT/CN2022/086755, filed on April 14, 2022; PCT/CN2022/087382, filed on April 18, 2022; PCT/CN2022/087383, filed on April 18, 2022.
It’s noted instant claimed compound with fused 1, 4-oxezepane, e.g. the elected species, are disclosed in PCT/CN2022/081022, filed on March 15, 2022 , but not in PCT/CN2022/077678 filed on February 24, 2022 or other earlier priority documents.
Information Disclosure Statement
The information disclosure statements filed 02/16/2024, 03/08/2024 and 09/02/2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the relevant reference listed in IDS are being considered by the examiner.
Claim Objections
Claims 111-133 are objected to because of the following informalities:
There are typo errors in claims 126 and 132, “ The compound, a The compound” .
Claim 111 recites “ A compound or a deuterated derivative, stereoisomer, or pharmaceutically acceptable salt of said compound or stereoisomer, wherein said compound is of the following formula”. The recitation of “said compound” is repetitive. For clarity, it should read: A compound or a deuterated derivative, stereoisomer, or pharmaceutically acceptable salt thereof, wherein the compound is following formula.
Dependent claims 112-133 recite “The compound, deuterated derivative, stereoisomer, or pharmaceutically acceptable salt”. For clarity, it should read: The compound, deuterated derivative, stereoisomer, or pharmaceutically acceptable salt thereof. Dependent claims should not recite “according to claim...” in bold.
For consistency, delete the comma following “wherein,” in claims 111-132, and use comma instead of semicolon in claims 112-119.
Specification
The spacing of the lines of the specification is such as to make reading difficult. New application papers with lines 1 1/2 or double spaced (see 37 CFR 1.52(b)(2)) on good quality paper are required.
The disclosure is objected to because numbering of compounds in instant specification is NOT consistent and confusing. As noted in preceding Election/Restriction section, the compounds IDs in Table 18 are not consistent with instant Example numbers. The elected species, compound ID# 51 in Table 18 (page 56) is Compound 33 disclosed in Example 33 ( page 115 ) of instant specification, which has different structure from Compound 51 disclosed in Example 51(page 128) of instant specification. It’s not clear what compound ID/numbers and corresponding structure are used in activity Table 22 and 24 .
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Instant specification disclosed vast variety of chemical compounds with complex structures and lengthy names. The specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification.
Claim Rejections - 35 USC § 112
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.
Claims 111-133 are rejected under 35 U.S.C. 112(a) 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.
Claims 111-133 recite “A compound or a deuterated derivative...wherein each of Rs1 is independently selected from halogens; z1 is 0,1 or 2...”.
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Instant specification does not define “deuterated derivative” and does not disclose any embodiments/working example comprising deuterated moieties/group. An ordinary skilled in the art would not know what “deuterated derivative” are encompassed by instant claims.
Regarding the fused oxazepane moiety, it’s not clear where the Rs1 group is located, on the 1, 4-oxazepane ring or on the fused cyclopropyl ring or both. Instant specification does not disclose any working example comprising Rs1 (z1 is 1 or 2) at the fused cyclopropyl ring. Instant specification does not disclose any moieties/working example comprising fused cyclopropyl oxazepane and Rs1 (z1 is 1 or 2) on the 1, 4-oxazepane. Instant specification does not disclose embodiments/working example comprising fused oxazepane ring and R4a is CN, NH2, or SH. Instant disclosure does not fully support instant claimed compounds comprising fused oxazepane and deuterated derivative.
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.
Claim 126-131 are rejected under 35 U.S.C. 112(b) 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.
Claims 126-131 recite limitation “R4 is selected from...”. Claims 126-131 depend on claims 114 to 119, respectively, which indirectly depend on claim 111. However, independent claim 111 does not recite R4 moiety in the compound formula. Thus, there is insufficient antecedent basis for limitation “R4” in the claims.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 126-131 are rejected under 35 U.S.C. 112(d) as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claims 126-131 are drawn to compounds comprising R4 selected from specific substituted naphthalene ring. Claims 126-131 depend on claims 114 to 119, respectively, which indirectly depend on claim 111. However, independent claim 111 does not recite R4 moiety in the compound formula. Thus, claims 126-131 are directed to subject matter not recited in the claim upon which they depend.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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.
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 111-133 are rejected under 35 U.S.C. 103 as being unpatentable over Wang et al. (WO 2022/132200 A1, Applicant’s IDS dated 02/16/2024).
Wang teaches azaquinazoline compound of Formula I, IA, or salt thereof as pan-KRas inhibitors, pharmaceutical composition comprising aforementioned azaquinazoline compounds, activity thereof and method of treating cancer with aforementioned compounds (See abstract, [00007], [00013]-[00014], [000086]-[0000192]; Examples 1-523; Table 2-4; claims 1-83).
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It’s noted
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moiety read on instant
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.
Regarding instant 1,4-dioxazepane moiety
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recited in claims 114-119, Wang teaches variety of embodiments of
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, wherein Y1 and Y2 forms oxazepane ring, two R7 on adjacent atoms optionally join to form a bond or a fused ring selected from C3-C6 cycloalkyl, optionally substituted with 1-4 R8 (See [000027], [0000105], [0000128], [0000189], claims 1-2, 59 etc. ) and R8 is independently halogen (See [000029], [0000108], [0000130], etc. ) (which reads on instant claimed Rs1).
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Wang teaches compounds comprising the core structure of instant 1,4 -oxazepane compounds,
and species that are similar to instant claimed compounds, e.g. Example 200, 201, 270, 290, 315, 316, 345, 386, 391, 419, 420, 500, etc. .
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Regarding instant claims 120-132, Wang teaches A moiety is naphthyl optionally substituted with 1-4 R1 wherein R1 is halogen, hydroxy, C2-C4 alkenyl, C2-C4 alkynyl, etc. (See [0000116] , [0000119]) Wang Compound 201 and other exemplary compounds comprising substituted naphthalene ring read on instant compound wherein R4a is F, OH, and
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.
Regarding the pharmaceutical composition of instant claim 133, Wang teaches pharmaceutical composition comprising azaquinazoline compounds and pharmaceutically acceptable carrier (See [0000193] –[0000199]).
Wang collectively teaches 1,4-oxazepane azaquinazoline compounds as Kras inhibitors that are very similar to instant claimed compounds.
The difference between Wang’s exemplary compounds comprising 1,4-oxazepane ring and instant compounds is the fused 1,4-oxazepane
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. However, Wang teaches two R7 on adjacent atoms optionally join to form a fused ring selected from C3-C6 cycloalkyl, optionally substituted with 1-4 R8 (See [000027], [0000105], [0000128], [0000189], claims 1-2, 59 etc. ) and R8 is independently halogen (See [000029], [0000108], [0000130], etc. ) (which reads on instant claimed Rs1).
According to MPEP 2144.09 (I), 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 obvious for one of ordinary skill in the art to further explore more 1,4-oxazepane azaquinazoline compounds as Kras inhibitors based on collective teachings of Wang, together with experimentation/optimization based on general knowledge of structure similarity/ bioisosteric modification of SAR study, and arrive at instantly claimed invention with reasonable expected success. A skilled artisan would be motivated to explore more Kras inhibitor based on Wang’s azaquinazoline scaffold and reasonably expect the alternative 1,4-oxazepane azaquinazoline compounds exhibit similar activity.
For example, Wang Compound 201 and 391 (with good KRas binding activity IC50<=2nM in Table 2) could have been modified at R7 on the 1,4-oxazepane ring by introducing fused cyclopropyl ring as taught by Wang and arrive at instant elected species.
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One of ordinary skill in the art would have had reasonable expectation of success in producing instant claimed invention based on the combined teaching of prior art, together with general knowledge of structure similarity/ bioisosteric modification for SAR study. 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 111-133 are rejected under 35 U.S.C. 103 as being unpatentable over Yamano et al. ( WO2023018809 A1, Applicant’s IDS dated 09/02/2025).
Yamano teaches heterocyclic compound of Formula I, II, III, IV, V or salt thereof as KRas inhibitors, pharmaceutical composition thereof and method of treating cancer with aforementioned compounds (See abstract, page 4, lines 5-25; page 5, lines 1-16; page 28, lines 1-5; Embodiments 1-224; Table 2, 5, 8; Example 1-80; claims 1-58).
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Yamano teaches embodiments comprising variety of
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e.g.
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(See page 18, lines 16-19), and 1,4-oxazepanes
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etc. (See page 21, lines 9- 12; claim 38).
Regarding instant claims 119-131, Yamano teaches embodiments comprising variety of naphthalene ring, wherein R4a is F, OH,
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, etc. (See page 10, lines 12-20; claims 3-9, 22-23), e.g.
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Regarding claim 133, Yamano teaches pharmaceutical composition comprising compound of Formula I and pharmaceutically acceptable carrier (See page 71, lines 10-30; claim 43).
Yamano teaches compound species that are very similar to instant claimed compounds (See Table 2, 5 and 8, claim 41),
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Yamano collectively teaches 1,4-oxazepane compounds as Kras inhibitors that are very similar to instant claimed compounds.
The difference between Yamano’s exemplary compounds comprising 1,4-oxazepane ring and instant compounds is the fused 1,4-oxazepane
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. However, Yamano teaches two Rx taken
together with adjacent carbon atoms can form a C3-7 cycloalkyl, wherein each C3-7 cycloalkyl is further
substituted with 0-3 occurrences of Ry (Ry is halogen) (See page 4, line 18-20) (which reads on instant claimed Rs1). Yamano teaches embodiments comprising
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which is homolog of
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.
According to MPEP 2144.09 (I), 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).
According to MPEP 2144.09 (II), Compounds which are position isomers (compounds having the same radicals in physically different positions on the same nucleus) or homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977).
It would have been obvious for one of ordinary skill in the art to further explore more 1,4-oxazepane Kras inhibitors based on collective teachings of Yamano, together with experimentation/optimization based on general knowledge of structure similarity/ bioisosteric modification of SAR study, and arrive at instantly claimed invention with reasonable expected success. A skilled artisan would be motivated to explore more Kras inhibitor based on Yamano’s scaffold and reasonably expect the alternative 1,4-oxazepane azaquinazoline compounds exhibit similar activity.
For example, Yamano Compound 41 could be modified to fused cyclopropyl 1,4-oxazepane, which is also homolog of Yamano Compound 66,
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, which can be further modified to instant elected species.
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One of ordinary skill in the art would have had reasonable expectation of success in producing instant claimed invention based on the combined teaching of prior art, together with general knowledge of structure similarity/ bioisosteric modification for SAR study. 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.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Jones et al. WO2022/248885 A2 (Applicant’s IDS dated 09/02/2025). Jones teaches Kras inhibitors comprising the core structure of instant claimed compounds and compound species that are very similar to instant compounds (See claim 16), e.g.
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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 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, 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.
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/L.M./ Examiner, Art Unit 1628
/AMY L CLARK/ Supervisory Patent Examiner, Art Unit 1628
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