Detailed Action
The present office action is in response to the application filed on 23 Dec 2025.
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 .
Status
Claims 2-7 of the pending application have been examined on the merits. Claims 9-10 remain withdrawn. Acknowledgment is made of the cancellation of claims 1 and 8.
Priority
Applicants identify the instant application, Serial #: 17/793,571, filed 18 Jul 2022, as a National Stage Entry of International Patent Application #: PCT/CN2021/071375, filed 13 Jan 2021, which claims foreign priority from Foreign Application #: CN202010056202.3, filed 19 Jan 2020.
Response to Applicant Arguments
Acknowledgement is made of the remarks filed 23 Dec 2025.
The objection to claims 1-2 have been rendered moot following applicant amendments.
The rejection of claim 1 is rendered moot following the cancellation of claim 1.
Regarding the rejection of claims 2-7 under 35 U.S.C. § 103 over WO 2016/203405 (provided in IDS 07/18/22), hereinafter ‘405, further in view of WO 2021/043077 (provided in the office action mailed 29 Sep 2025), hereinafter ‘077, applicant arguments have been fully considered but are not persuasive.
Applicant argues on pgs. 8-10 of the remarks that the compounds found in '405 demonstrate unremarkable activity in inhibiting SHP2 activity. Applicant argues that a person of ordinary skill in the art would not have been motivated to select the compound of '405 as lead compounds given their unremarkable activity and unfavorable structure-activity relationships. Applicant further argues that the artisan have been motivated to arrive at the present compounds by way of the cited compounds and to anticipate the resulting compounds would be useful in modulating or inhibiting SHP2 activity with a reasonable expectation of success.
Applicant arguments are not a replacement for evidence (see MPEP § 2145(I)). As such, it is unclear where '405 demonstrates "unremarkable activity" and "unfavorable structure-activity relationships" of the SHP2 inhibitors provided as an example. '405 states that the example compounds have activity as SHP2 inhibitors. Further, the compounds taught in '077 have similar utility as SHP2 inhibitors.
Applicant argues on pg. 10 of the remarks that '077 teaches that the common structure of the disclosed compounds is the pyrazinyl group and that it is the presence of the pyrazine ring that confers SHP2 inhibitory activity. Applicant argues that the artisan would not have been able to replace the pyrazinyl group of the compounds taught in '077 with the pyrimidone core of the instant compounds without undue experimentation.
'077 is not relied on for teaching the pyrimidone core. '077 contains compounds which have activity as SHP2 inhibitors with the same indazole moiety as the instant claims. The motivation to make the instantly elected compound from '405 and the indazole moiety in '077 derives from the expectation that structurally similar compounds will possess similar activities (see MPEP § 2144.09(I)-2144.09(II) and the rejection under 35 U.S.C. § 103 below).
Applicant argues on pg. 11 of the remarks that '077 teaches compounds containing structurally similar fused rings corresponding to the A and B rings in the instant formula (II) exhibit unremarkable SHP2 inhibitory activity. Applicant further argues that most of the compounds with fused structures in '077 lack experimental data indicating that these compounds are not central to the biological activity study in '077.
Applicant arguments are not a replacement for evidence (see MPEP § 2145(I)). As such, it is unclear where '077 demonstrates "unremarkable activity" for the SHP2 inhibitor provided as an example.
Applicant argues on pg. 12 of the remarks that the first thing needing to be determined if the replacement of the pyrimidone group in '405 with the pyrazine group is responsible for SHP2 inhibitory activity in '077 because there is no definitive teaching in '405 that the pyrimidone group is responsible for SHP2 inhibitory activity.
This is not persuasive. '077 is not relied on for teaching the pyrimidone core. '077 contains compounds which have activity as SHP2 inhibitors with the same indazole moiety as the instant claims. The motivation to make the instantly elected compound from '405 and the indazole moiety in '077 derives from the expectation that structurally similar compounds will possess similar activities (see MPEP § 2144.09(I)-2144.09(II) and the rejection under 35 U.S.C. § 103 below).
Applicant argues on pg. 13 of the remarks that a person of ordinary skill in the art would not have been motivated by the presence of a five-membered heteroaromatic group fused with a phenyl group in the compounds in '077 to believe that compounds with similar activity can be achieved by simply replacing the corresponding part of the compounds in '405 with a five-membered heteroaromatic group fused with a phenyl group.
This is not persuasive. Applicant arguments are not a replacement for evidence (see MPEP § 2145(I)). The references together teach all the elements found in the instantly elected species and so the rejection under 35 U.S.C. § 103 is maintained.
In light of the discussion above, the rejection of claims 2-7 under 35 U.S.C. § 103, as obvious over ‘405 and 077 is maintained for the reasons of record and restated below.
Claim Rejections - 35 USC § 112
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 2 and 4-7 is 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. This rejection is necessitated by applicant amendments.
Claims 2 and 4-7 contain Markush groupings which do not have the coordinating conjunctions “and” or “or” to properly limit the alternatives defined in the list. Specifically, the claims list “and mixtures thereof” where it should be “or mixtures thereof.” See MPEP § 2117(I). Applicant may overcome this rejection by adding the proper coordinating conjunction to each Markush group in need of one.
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.
Claim(s) 2-7 is/are rejected under 35 U.S.C. 103 as being unpatentable over ‘405 further in view of ‘077.
Applicant has elected the following species which reads on instant claims 1-7:
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121
278
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‘405 teaches compounds of reference Formula I which have SHP2 inhibiting activity (Abstract; paragraph [005]; claim 1):
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155
323
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‘405 further teaches that compounds may be included in pharmaceutically acceptable compositions which include a compound of Formula I and a pharmaceutically acceptable carrier (paragraph [0082]) and that compounds of Formula (I) may be administered in combination with other drugs (paragraph [00148]-[00226]). Specific examples of compounds Formula I include:
Compound #
Compound Structure
IC50 for SHP2 inhibition (paragraphs [00457]-[00459])
Compound 78 (Table 12)
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109
193
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12 nM
Compound 102 (Table 13)
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159
192
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10 nM
Compound 103 (Table 13)
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154
170
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15 nM
Compound 105 (Table 13)
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154
177
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8 nM
Compound 106 (Table 13)
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154
175
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30 nM
Compound 107 (Table 13)
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165
190
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146 nM
The above structures share the pyrimidone core and spiro moiety with the instantly elected invention. Furthermore, Compounds 102-103 and 105-107 contain a chlorine in the ortho position relative to the thiol bond of the benzene or pyrimidine group. Compound 78 teaches a bicyclic structure in the same place as the indazole of the instantly elected compound. ‘450 does not, however, teach the instantly elected compound.
‘077 teaches Example 59, TM182B as useful for inhibiting SHP2 activity with an IC50 of 14.2 nM (pg. 69; pg. 74).
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150
132
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MPEP § 2144.09(I) states that “a prima facie case of obviousness may be made when chemical compounds have very close structural similarities and similar utilities.”
MPEP § 2144.09(II) states that “compound which are position isomers (compounds having the same radicals in physically different position on the same nucleus)…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).”
Based on the teachings of ‘405 and ‘077 a person of ordinary skill in the art would find Compound 78, 102-103, and 105-107, found in ‘405, and TM182B, found in ‘077, to be of similar structure and utility and thus would swap the bicyclic moiety taught by ‘405 with the indazole moiety as taught in ‘077 to arrive at the following Compound IA which is a position isomer of the instantly elected compound:
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200
400
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The motivation to make the instantly claimed compounds from Compound IA derives from the expectation that structurally similar compounds would possess similar activity (i.e. they would be pharmacologically active SHP2 inhibitors) with potential for better bioavailability and lower side effects. There would be a reasonable expectation of success in producing and using the instantly claimed compounds and compositions in view of the compounds and compositions taught by ‘405 and ‘077.
A reference is good not only for what it teaches by direct anticipation but also for what one of ordinary skill in the art might reasonably infer from the teachings (In re Opprecht 12 USPQ 2d 1235, 1236 (Fed Cir. 1989); In re Bode 193 USPQ 12 (CCPA) 1976). In light of the foregoing discussion, the examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103. From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Conclusion
No claim is allowed. Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jonathan D. Mahlum whose telephone number is (703)756-4691. The examiner can normally be reached 8:30 AM - 5:00 PM ET, M-F.
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/J.D.M./Examiner, Art Unit 1625
/Andrew D Kosar/Supervisory Patent Examiner, Art Unit 1625