Prosecution Insights
Last updated: April 19, 2026
Application No. 18/007,776

RIPK1 INHIBITORS AND METHODS OF USE

Final Rejection §102§103§112
Filed
Dec 02, 2022
Examiner
HERNANDEZ, JACKSON J
Art Unit
1627
Tech Center
1600 — Biotechnology & Organic Chemistry
Assignee
Merck Sharp & Dohme LLC
OA Round
2 (Final)
50%
Grant Probability
Moderate
3-4
OA Rounds
3y 2m
To Grant
99%
With Interview

Examiner Intelligence

Grants 50% of resolved cases
50%
Career Allow Rate
15 granted / 30 resolved
-10.0% vs TC avg
Strong +51% interview lift
Without
With
+51.1%
Interview Lift
resolved cases with interview
Typical timeline
3y 2m
Avg Prosecution
87 currently pending
Career history
117
Total Applications
across all art units

Statute-Specific Performance

§101
2.4%
-37.6% vs TC avg
§103
34.9%
-5.1% vs TC avg
§102
11.8%
-28.2% vs TC avg
§112
24.7%
-15.3% vs TC avg
Black line = Tech Center average estimate • Based on career data from 30 resolved cases

Office Action

§102 §103 §112
DETAILED ACTION 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 of the Claims Claims 19-21 and 23-24 are pending in this application. Claims 1-18 and 22 have been cancelled by applicant. Claims 20-21 are withdrawn from consideration. Claims 19 and 23-24 are under examination herein. Claim Rejections - 35 USC § 102 The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action: A person shall be entitled to a patent unless – (a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention. (a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention. Claim 19 is rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Zhang et al. (WO 2020/103884 A1 – Published May 28th, 2020 – From IDS – previously cited) (“Zhang”). Regarding claim 19, Zhang discloses compounds 144 and 215 below, which match two of the instantly claimed compounds (pages 24 and 28). PNG media_image1.png 290 351 media_image1.png Greyscale PNG media_image2.png 187 422 media_image2.png Greyscale Claim Rejections - 35 USC § 103 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. Claims 19 and 23-24 are rejected under 35 U.S.C. 103 as being unpatentable over Zhang et al. (WO 2020/103884 A1 – Published May 28th, 2020 – From IDS – previously cited), as applied to claim 19. Further regarding claim 19, Zhang further discloses the compounds below [009], wherein R1 can be a C3-9 cycloalkyl or aryl, including substituted or unsubstituted phenyl, such as difluoro or fluoro phenyl [021-022]; R2 can be a C3-14 heterocyclic moiety with 1-3 heteroatoms; and R3 and R4 can be linked to form a 3-8 membered ring, as shown in the 102 section above. PNG media_image3.png 398 440 media_image3.png Greyscale Zhang discloses the preferred embodiments below, for example, which render the instant structures below obvious when the ring R1 is difluoro phenyl instead of phenyl, as with preferred embodiments 144 and 215 (shown in the 102-section) (Table 1, compounds 4 and 20, etc. pages 17-21): PNG media_image4.png 255 261 media_image4.png Greyscale PNG media_image5.png 218 337 media_image5.png Greyscale Sample instant compounds: PNG media_image6.png 97 137 media_image6.png Greyscale PNG media_image7.png 116 183 media_image7.png Greyscale Therefore, Zhang discloses a fairly narrow genus of compounds which encompasses the instant compounds. Thus, one having ordinary skill in the art would have found the claimed compounds prima facie obvious, since they are generically embraced Zhang’s disclosed formula; In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971). See MPEP 2144.08. The requisite motivation for arriving at the claimed compounds stems from the fact that they fall within the generic class of compounds disclosed by Zhang. Accordingly, one having ordinary skill in the art would have been motivated to prepare any of the compounds embraced by the disclosed generic formula, including those encompassed by the claims. Applicant is advised that a novel useful compound that is isomeric with the prior art compound is unpatentable unless it possesses some unobvious or unexpected beneficial property not possessed by the prior art compound. In re Norris, 179 F.2d. 970, 84 USPQ 458 (CCPA 1970). Therefore, it would have been obvious to one of ordinary skill to expect similar properties of structurally similar compounds since they are suggestive of one another. It has been held that a compound, which is structurally isomeric with a compound of the prior art, is prima facie obvious absent unexpected results. In re Finely, 81 USPQ 383 (CCPA 1949); 84 USPQ 458 (CCPA 1950). With respect to stereoisomerism, it is noted that in Aventis Pharma Deutschland v. Lupin Ltd., 499 F.3d 1293 (Fed. Cir. 2007), the court also relied on the settled principle that in chemical cases, structural similarity can provide the necessary reason to modify prior art teachings. The Federal Circuit also addressed the kind of teaching that would be sufficient in the absence of an explicitly stated prior art-based motivation, explaining that an expectation of similar properties in light of the prior art can be sufficient, even without an explicit teaching that the compound will have a particular utility. The Federal Circuit cautioned that requiring such a clearly stated motivation in the prior art to isolate 5(S) ramipril ran counter to the Supreme Court' s decision in KSR. The court stated: [r]equiring an explicit teaching to purify the 5(S) stereoisomer from a mixture in which it is the active ingredient is precisely the sort of rigid application of the TSM test that was criticized in KSR. Id. at 1301 (See MPEP 2143). Regarding claims 23-24, Zhang discloses their compounds and pharmaceutically acceptable salts thereof can be administered as a sole active ingredient, and can be incorporated into pharmaceutical compositions that contain acceptable diluents or carriers ([0117] to [0118]). Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to formulate pharmaceutical compositions of Zhang’s compounds comprising pharmaceutically acceptable salts and/or acceptable carriers. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of Zhang’s disclosure that their compounds are meant for administration for the treatment of RIPK1 related conditions ([053] to [054]) and that formulations may contain acceptable diluents and carriers. Response to Arguments Claims Claim amendments are acknowledged. No new matter has been introduced. Claim Rejections - 35 USC § 112(b) Applicant’s arguments, see page 13, filed 12/15/2025, with respect to 35 USC § 112(b) rejections have been fully considered and are persuasive. The 35 USC § 112(b) rejections of the claims have been withdrawn. Claim Rejections - 35 USC § 102 Applicant's arguments filed 12/15/2025 have been fully considered but they are not persuasive. Applicant states claim 19 is novel. The cited art clearly discloses compounds which anticipate the instantly claimed compounds. Claims stand rejected under 35 USC § 102(a)(1) and (a)(2). Claim Rejections - 35 USC § 103 Applicant's arguments filed 12/15/2025 have been fully considered but they are not persuasive. Applicant states the cited art does not disclose or suggest the particular combination of elements found in claim 19. Zhang discloses the compounds below [009], wherein R1 can be a C3-9 cycloalkyl or aryl, including substituted or unsubstituted phenyl, such as difluoro or fluoro phenyl [021-022]; R2 can be a C3-14 heterocyclic moiety with 1-3 heteroatoms; and R3 and R4 can be linked to form a 3-8 membered ring, as shown in the 102 section above. PNG media_image3.png 398 440 media_image3.png Greyscale Zhang discloses the preferred embodiments below, for example, which render the instant structures below obvious when the ring R1 is difluoro phenyl instead of phenyl, as with preferred embodiments 144 and 215 (shown in the 102-section) (Table 1, compounds 4 and 20, etc. pages 17-21): PNG media_image4.png 255 261 media_image4.png Greyscale PNG media_image5.png 218 337 media_image5.png Greyscale Sample instant compounds: PNG media_image6.png 97 137 media_image6.png Greyscale PNG media_image7.png 116 183 media_image7.png Greyscale Therefore, Zhang discloses a fairly narrow genus of compounds which encompasses the instant compounds. Thus, one having ordinary skill in the art would have found the claimed compounds prima facie obvious, since they are generically embraced Zhang’s disclosed formula. The requisite motivation for arriving at the claimed compounds stems from the fact that they fall within the generic class of compounds disclosed by Zhang. Accordingly, one having ordinary skill in the art would have been motivated to prepare any of the compounds embraced by the disclosed generic formula, including those encompassed by the claims. Applicant is reminded that a novel useful compound that is isomeric with the prior art compound is unpatentable unless it possesses some unobvious or unexpected beneficial property not possessed by the prior art compound. Therefore, it would have been obvious to one of ordinary skill to expect similar properties of structurally similar compounds since they are suggestive of one another. It has been held that a compound, which is structurally isomeric with a compound of the prior art, is prima facie obvious absent unexpected results. With respect to stereoisomerism, it is noted that in Aventis Pharma Deutschland v. Lupin Ltd., 499 F.3d 1293 (Fed. Cir. 2007), the court also relied on the settled principle that in chemical cases, structural similarity can provide the necessary reason to modify prior art teachings. The Federal Circuit also addressed the kind of teaching that would be sufficient in the absence of an explicitly stated prior art-based motivation, explaining that an expectation of similar properties in light of the prior art can be sufficient, even without an explicit teaching that the compound will have a particular utility. The Federal Circuit cautioned that requiring such a clearly stated motivation in the prior art to isolate 5(S) ramipril ran counter to the Supreme Court' s decision in KSR. The court stated: [r]equiring an explicit teaching to purify the 5(S) stereoisomer from a mixture in which it is the active ingredient is precisely the sort of rigid application of the TSM test that was criticized in KSR. Id. at 1301. Conclusion Any inquiry concerning this communication or earlier communications from the examiner should be directed to JACKSON J HERNANDEZ whose telephone number is (571)272-5382. The examiner can normally be reached Mon - Thurs 7:30 to 5. Examiner interviews are available via telephone 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, Kortney L. Klinkel can be reached at (571) 270-5239. 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. /JACKSON J HERNANDEZ/Examiner, Art Unit 1627 /Kortney L. Klinkel/Supervisory Patent Examiner, Art Unit 1627
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Prosecution Timeline

Dec 02, 2022
Application Filed
Aug 10, 2025
Non-Final Rejection — §102, §103, §112
Dec 15, 2025
Response Filed
Jan 18, 2026
Final Rejection — §102, §103, §112 (current)

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Study what changed to get past this examiner. Based on 5 most recent grants.

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Prosecution Projections

3-4
Expected OA Rounds
50%
Grant Probability
99%
With Interview (+51.1%)
3y 2m
Median Time to Grant
Moderate
PTA Risk
Based on 30 resolved cases by this examiner. Grant probability derived from career allow rate.

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