FINAL REJECTION
Receipt is acknowledged of Applicants' Amendments and Remarks, filed May 20, 2026.
Rejections and/or objections not reiterated from previous Office Actions are hereby withdrawn. The rejections and/or objections set forth below are either maintained or newly applied, and constitute the complete set presently applied to the instant claims.
STATUS OF THE CLAIMS
Claims 7 and 21 have been canceled.
Claim 18 has been amended to correct a typographical error.
No new claims have been added.
Claims 2, 5, 9, and 18-20 stand withdrawn as drawn to nonelected inventions and/or species.
Thus, claims 1, 3, 4, 6, 8, 10-17, and 22 now represent all claims currently pending and under consideration.
INFORMATION DISCLOSURE STATEMENT
The information disclosure statement (IDS) submitted on May 20, 2026 was filed after the mailing date of the non-final action on Jan. 9, 2026. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
MAINTAINED REJECTIONS
The following rejection is maintained from the previous Office Action dated Jan. 9, 2026, on the ground that the references cited therein continue to read on the limitations of the amended 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 nonobviousness.
Claims 1, 3, 4, 6, 8, 10-17, and 22 stand rejected under 35 U.S.C. 103(a) as being unpatentable over Bie et al. (WO2019/034128).
Bie et al. disclose pyrrolotriazine derivatives of formula (I) and methods of use thereof as a therapeutic agent, particularly as a c-KIT inhibitor (abstract).
In particular, Bie et al exemplify compound 22 (table, p. 11), shown side-by-side with claimed formula (I) and the elected compound species for comparison:
Claimed Formula (I)
Elected Species (Compound 1)
Bie et al. Compound 22
PNG
media_image1.png
364
300
media_image1.png
Greyscale
PNG
media_image2.png
217
214
media_image2.png
Greyscale
PNG
media_image3.png
200
400
media_image3.png
Greyscale
Compound 22 of Bie et al. reads on claimed formula (I) as recited by claims 1, 16, and 22, and claimed formula (III) as recited by claims 3, 6, 8, and 10-15, to the extent that Y is N; Z is CH; X1 is N, X2 is C, a is a single bond, and b is a double bond; and B is NH2.
The compounds of Bie et al. are disclosed in pharmaceutical compositions comprising a therapeutically effective amount of a compound of formula (I), or a stereoisomer, tautomer or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, excipient or combination thereof (paras, [0178], [0226]; claim 27), as recited by claim 17.
Compound 22 of Bie et al. differs from the claimed compounds only in that the pyrazolyl ring is substituted by methyl, rather than A, having the structural formula,
PNG
media_image4.png
184
260
media_image4.png
Greyscale
as recited by claim 1;
and as required by the elected species, wherein A is hydroxyethyl (-CH2CH2OH).
However, Bie et al. disclose compound 22 as a species of generic formula (I),
PNG
media_image5.png
200
400
media_image5.png
Greyscale
wherein R4 is selected from, e.g., heteroaryl (e.g., pyrazolyl), which is optionally further substituted by one or more substituents selected from, e.g., alkyl (para. [0018]; claim 1).
Bie et al. define "alkyl" as a saturated aliphatic hydrocarbon group including C1-20 straight chain or branched chain, which can be substituted or unsubstituted (para. [0187]; emphasis added).
Bie et al. disclose that, unless otherwise specified, the terms "substitution" or "substituted" refer to the substitution of a group by one or more groups selected from, e.g., hydroxyl (paras. [0219]-[0220]; emphasis added).
Thus, the compounds of Bie et al. encompass both unsubstituted alkyl (methyl) and substituted alkyl (hydroxyethyl) pyrazole ring substituents as equivalent alternatives.
Further, the compounds of Bie et al. are disclosed and claimed for use in treating diseases mediated by wildtype c-KIT or PDFGRα, or mutated c-KIT or PDFGRα, e.g., gastrointestinal stromal tumors (GIST), systemic mast cell hyperplasia, acute myeloid leukemia, various cancers, mast cell tumors, or leukemia (claims 28 and 30).
Therefore, it would have been predictable to one of ordinary skill in the art as of the effective filing date to modify the pyrazole substituent of compound 22 of Bie et al., from methyl to hydroxyethyl, to arrive at the elected compound with a reasonable expectation of success, because the compounds of Bie et al. share extremely close structural similarity with the claimed compounds, differing only in the substituents on the identical pharmacophore, and are disclosed to have the same mechanism of action, as inhibitors of c-KIT and PDGFRα, as well as utility for treating the same diseases, e.g., gastrointestinal stromal tumors and systemic mastocytosis.
As recognized by MPEP § 2144.09, a prima facie case of obviousness may be made when chemical compounds have (1) very close structural similarities and (2) 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); see also In re Dillon, 919 F.2d 688, 16 USPQ2d 1897 (Fed. Cir. 1990) (and cases cited therein).
RESPONSE TO ARGUMENTS
Applicant's arguments filed May 20, 2026 have been fully considered but they are not persuasive.
Applicant contends that R4 in Formula (I) of Bie et al. does not encompasses pyrazolyl substituted with hydroxyalkyl (or hydroxyethyl, as in the elected species). Bie et al. define R4 in para. [0018] and claim 1 as follows:
R⁴ is selected from alkyl, cycloalkyl, heterocyclic, aryl and/or heteroaryl, wherein the alkyl, cycloalkyl, heterocyclic, aryl or heteroaryl group is optionally further substituted by one or more substituents selected from halogen, nitro, cyano, alkyl, cycloalkyl, heterocyclic, aryl, heteroaryl, -OR8, -NR⁶R⁷, C(O)NR6R⁷, C(O)R⁸, OC(O)R⁸, -S(O)₂NR⁶R⁷ and/or -NR6C(O)R⁷.
Applicant contends that R⁴ can be a heteroaryl which is optionally substituted with a recited list of substituents, which includes alkyl and OR⁸ as separate substituents for R⁴, but it does not include alkyl substituted with hydroxy (i.e. hydroxylalky1).
Accordingly, the Examiner's position that Formula (I) encompasses compounds with pyrazolyl substituted with hydroxyalkyl is incorrect because Bie does not contemplate substituted alkyl (hydroxyethyl) as the possible substituents allowed for the heteroaryl of R⁴. Thus, Applicant contends that Bie et al. does not provide any motivation to replace the methyl group in Compound 22 with hydroxyethyl (Remarks, pp. 28-29).
In response, it is acknowledged that Bie et al. do not expressly include hydroxyalkyl as a substituent of R4. For example, in Compound 22 of Bie et al., R4 is heteroaryl (e.g., pyrazolyl), further substituted by alkyl (methyl) (para. [0018]; claim 1).
However, as discussed above, Bie et al. define "alkyl" as a saturated aliphatic hydro-carbon group, such as C1-20 straight or branched chain, which can be substituted or unsubstituted (para. [0187]; emphasis added).
Bie et al. disclose that, unless otherwise specified, the terms "substitution" or "substituted" refer to the substitution of a group by one or more groups selected from, e.g., hydroxyl (paras. [0219]-[0220]; emphasis added).
Thus, Bie et al. explicitly disclose, teach, and suggest both unsubstituted alkyl (e.g., methyl) and substituted alkyl (e.g., hydroxyethyl) as pyrazole ring substituents.
In addition, closely related prior art such as Zhang et al. (WO 2015/057873, cited on the IDS dated 1/26/2024) disclose c-KIT inhibitors of formula (I),
PNG
media_image6.png
282
128
media_image6.png
Greyscale
wherein Z is, e.g., heteroaryl (typically pyrazolyl), substituted with 0-5 RC, wherein RC is selected from, e.g., C1-6 hydroxyalkyl (claim 1).
Further, Zhang et al. exemplify compound 105 having a hydroxyalkyl substituent as a pyrazole ring substituent (see table p. 40):
PNG
media_image7.png
314
354
media_image7.png
Greyscale
The compounds of Zhang et al. are disclosed to have the same mechanism of action as the claimed compounds and the compounds of Bie et al., as inhibitors of c-KIT and PDGFRα, as well as utility for treating the same diseases, e.g., mastocytosis, gastrointestinal stromal tumors and acute myeloid leukemia (claims 17-19).
Thus, hydroxyalkyl substituents on the pyrazole ring of this class of pyrrolotriazine c-KIT inhibitors were known in the art.
A prima facie case of obviousness based on structural similarity is rebuttable by proof that the claimed compound(s) possess unexpectedly advantageous or superior properties. In re Papesch, 315 F.2d 381, 137 USPQ 43 (CCPA 1963). However, Applicant has not argued or pointed out any such evidence of unexpected results.
CONCLUSION
No claims are allowed.
THIS ACTION IS MADE FINAL. 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 SARA E. TOWNSLEY whose telephone number is 571-270-7672. The examiner can normally be reached on Mon-Fri from 10:00 am to 6:00 pm (EST). If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Jeff S. 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.
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.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://portal.uspto.gov/external/portal. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free).
/SARA E. TOWNSLEY/Examiner, Art Unit 1629
Prosecution Insights