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 .
Priority
The instant application was received 22 March 2024; it is a national stage application of PCT/CN2022/131601, filed 14 November 2022, and claims foreign priority to CN202111105717.9, filed 22 September 2021. Acknowledgment is made of Applicant’s claim for foreign priority and certified copies of the priority documents have been received.
Restriction/Election
Requirement for Restriction/Election was mailed 02 June 2026.
Applicant’s Response to Requirement for Restriction/Election was received 02 August 2026.
Applicant’s election with traverse of Group I (Claims 14, 22-27, and 30) and Compound 75, indicating claims 14, 22-27, and 30 read on the elected species, in the Response filed 2 August 2026 is acknowledged.
PNG
media_image1.png
83
180
media_image1.png
Greyscale
Regarding the Requirement for Restriction, Applicant argues CAS Registry Number 2468950-65-2, shown below, lacks a suggestion to use CAS Registry Number 2468950-65-2 in the pharmaceutical field, nor does CAS Registry Number 2468950-65-2 disclose preparation methods or biological activity.
This is not found persuasive because the compound corresponding to CAS Registry Number 2468950-65-2, shown below, provides predicted solubility data, which implies said compound may be included in a composition. Phrased differently, by providing solubility data, CAS Registry Number 2468950-65-2 teaches an aqueous solution (i.e., a composition).
PNG
media_image2.png
209
405
media_image2.png
Greyscale
PNG
media_image3.png
597
701
media_image3.png
Greyscale
The requirement is still deemed proper and is therefore made FINAL.
The claims in Group III (i.e., methods for inhibiting RIPK1 kinase activity in a subject in need thereof and methods for preventing and/or treating RIPK1-related disease in a subject in need thereof using instantly claimed compounds) and the claims that do not read on the elected species, which are claims 28-29 and 31-39, are withdrawn.
In accordance with MPEP § 803.02, if upon examination of the elected species, no prior art is found that would anticipate or render obvious the instant invention based on the elected species, the search of the Markush-type claim will be extended. If prior art is then found that anticipates or renders obvious the non-elected species, the Markush-type claim will be rejected. It should be noted that the 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 reexamined. 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 reexamination that renders obvious or anticipates the amended Markush-type claim, the claim will be rejected and the action made final.
As per MPEP § 803.02, the Examiner will determine whether the entire scope of the claims is patentable.
Status of the Claims
The listing of claims filed 02 August 2026 has been examined.
Claims 14 and 22-39 are pending.
Claim 14 is amended.
Claims 22-39 are newly added.
Claims 28-29 and 31-39 are withdrawn from further consideration pursuant to 37 CFR § 1.142(b), as being drawn to a non-elected invention and species.
Claims 1-13 and 15-21 are cancelled.
Claims 14, 22-27, and 30 are examined on the merits.
Information Disclosure Statement
The Information Disclosure Statements (IDSs) filed on 02 August 2026, 22 November 2025, and 16 October 2024 are acknowledged and have been considered.
Claim Objections
Claims 14 and 22-23 are objected to because of the following informalities:
Claim 14 recites, “…2) C1-C4 alkyl, C3-C7 cycloalkyl, substituted and unsubstituted 3-8 membered heterocyclyl…” [Emphasis added.] This appears to be a typographical error, as a heterocyclyl cannot simultaneously be both substituted and unsubstituted. Examiner recommends changing “and” to “or”. There are numerous instances throughout the claims (i.e., Claims 14 and 22-23), which recite “substituted and unsubstituted”.
Claim 14 recites, “…1) substituted and unsubstituted C6-C10 aryl, substituted 4-10 membered heteroaryl; 2) C1-C4 alkyl…” The word “or” appears to be missing immediately following the semicolon. Examiner recommends amending to, “…substituted 4-10 membered heteroaryl; or…” or similar.
Appropriate correction is requested.
Claim Rejections - 35 USC § 112(d)
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.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], 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.
Claim 22 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, 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.
Claim 22 recites, “…X is -CO-, -SO2-, or C1-C4 alkyl…” [Emphasis added.] However, claim 14, upon which claim 22 depends, recites, “…X is -CO-, -SO2-, -(CH2)nSO2-, or -NHCO-…” Thus, claim 14 fails to indicate X can be C1-C4 alkyl and, consequently, claim 22 improperly broadens the scope of claim 14 by indicating X can be C1-C4 alkyl.
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
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 14, 22-27, and 30 are rejected under 35 U.S.C. 103 as being unpatentable over Zhuo (US 2007/0129345 A1; IDS dated 22 November 2025, Cite No. 1).
Regarding claims 14 and 22-27, Zhuo teaches 11-β hydroxyl steroid dehydrogenase type 1 (11βHSD1) inhibitors as well as pharmaceutical compositions comprising said inhibitors (p. 1, ¶ [0002]), which have a generic structure (p. 36, Claim 1), shown below:
PNG
media_image4.png
124
110
media_image4.png
Greyscale
Wherein Q is –(CRaR2)m-A, Ra and R2 may be H, m is 0-3, and A is optionally substituted cycloalkyl, heterocycloalkyl, or heteroaryl (p. 36-38, Claim 1). Thus, Q may comprise a carbon chain having varying lengths. Additionally, Zhuo discloses various exemplary compounds, such as 8-Benzoyl-2-cyclohexyl-2,8-diazaspiro[4.5]decan-1-one (p. 20, ¶ [0253], Example 6), shown below:
PNG
media_image5.png
127
306
media_image5.png
Greyscale
In 8-Benzoyl-2-cyclohexyl-2,8-diazaspiro[4.5]decan-1-one, A is C2 alkylene, t is 1, X is -CO-, R1 is phenyl, and R2 is C6 cycloalkyl. Note the instantly recited compounds require an additional -CH2- on the N in the 5-membered ring.
Zhuo suggests preparing a composition comprising 8-Benzoyl-2-cyclohexyl-2,8-diazaspiro[4.5]decan-1-one and a pharmaceutically acceptable carrier (p. 42, Claim 61). The excipient may be a lubricating agent, like talc or magnesium stearate, a wetting agent, an emulsifying agent, a suspending agent, a preserving agent, a sweetening agent, and/or a flavoring agent (p. 16-17, ¶ [0220]).
Zhuo does not explicitly teach an exemplary compound having an instantly recited structure of Formula (I).
Prior to the filing of the instant application, a person having ordinary skill in the art (PHOSITA) following the teachings of Zhuo would have found it prima facie obvious to prepare a pharmaceutical composition comprising an instantly claimed compound of Formula (I) based on the teachings of Zhuo because Zhuo suggests preparing compositions comprising structurally similar compounds. For example, an instantly recited compound of Formula (I) is Compound 11 (Claim 30), shown below:
PNG
media_image6.png
108
177
media_image6.png
Greyscale
The only structural difference between instantly recited Compound 11 and Zhuo’s 8-Benzoyl-2-cyclohexyl-2,8-diazaspiro[4.5]decan-1-one is Compound 11 has an added -CH2- attached to the N in the 5-membered ring. However, as discussed above, Zhuo indicates Q can comprise an alkyl chain having 0-3 C atoms. Thus, although Zhuo fails to disclose an anticipatory species where Q is -CH2-, it would have been prima facie obvious to substitute an alkyl group between the lactam nitrogen and the cycloalkyl group because structurally similar compounds are expected to have similar properties and the genus of Zhuo teaches that m of Q can be 0-3, so compounds having a -CH2- linker and compounds which lack said linker would be expected to have similar properties. MPEP 2144.09(I) states, “A prima facie case of obviousness may be made when chemical compounds have very close structural similarities and similar utilities.” Compounds in Zhuo’s disclosed genus may be used for treating various diseases/disorders, such as cognitive impairment (p. 2-3, ¶ [0014]) and hypertension (p. 3, ¶ [0016]) as well as cardiovascular, renal, and inflammatory pathologies (p. 3-4, ¶ [0020]). Because Zhuo indicates m of Q can be 0-3, compounds wherein m is 0-3 would have been predicted to have similar utilities and a skilled artisan, in seeking to modify Zhuo’s compounds, would have known to try modifying m’s length.
Additionally, MPEP 2144.09(II-III) states, “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). See also In re May, 574 F.2d 1082, 197 USPQ 601 (CCPA 1978) (stereoisomers prima facie obvious); Aventis Pharma Deutschland v. Lupin Ltd., 499 F.3d 1293, 84 USPQ2d 1197 (Fed. Cir. 2007) (5(S) stereoisomer of ramipril obvious over prior art mixture of stereoisomers of ramipril.)… Prior art structures do not have to be true homologs or isomers to render structurally similar compounds prima facie obvious. In re Payne, 606 F.2d 303, 203 USPQ 245 (CCPA 1979) (Claimed and prior art compounds were both directed to heterocyclic carbamoyloximino compounds having pesticidal activity. The only structural difference between the claimed and prior art compounds was that the ring structures of the claimed compounds had two carbon atoms between two sulfur atoms whereas the prior art ring structures had either one or three carbon atoms between two sulfur atoms. The court held that although the prior art compounds were not true homologs or isomers of the claimed compounds, the similarity between the chemical structures and properties is sufficiently close that one of ordinary skill in the art would have been motivated to make the claimed compounds in searching for new pesticides.).”
Zhuo’s compound and, for example, instantly claimed Compound 11 have sufficiently close structural similarity that a PHOSITA would have expected both compounds to exhibit similar properties. Consequently, a PHOSITA would have been motivated to make the claimed compounds in searching for new inhibitors because Zhuo provides a motivation to make the structural modification (i.e., adding a -CH2-) which would have led a PHOSITA to arrive at an instantly claimed compound.
Regarding claim 30, Zhuo teaches all of the claimed elements as stated above.
Zhuo does not explicitly teach a compound which is a RIPK1 kinase inhibitor.
Prior to the filing of the instant application, a person having ordinary skill in the art (PHOSITA) following the teachings of Zhuo would have found it prima facie obvious to prepare a compound which the instant claims identify as an RIPK1 inhibitor because Zhuo discloses structurally similar compounds and a compound, meeting all the structural limitations required by claims 30 and/or 14, would be expected to exhibit the same activity as a RIPK1 kinase inhibitor. Inhibitory activity is a pharmacodynamic property. An identical compound must inherently have the same pharmacodynamic effect, even if not recognized in the art. “Products of identical chemical composition can not have mutually exclusive properties.” In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical compound or chemical composition and its properties are inseparable. Therefore, if the prior art teaches the claimed chemical structure, the properties Applicant discloses and/or claims are necessarily present. See MPEP § 2112.01. Consequently, in attempting to optimize a 11βHSD1 inhibitor disclosed by Zhuo and guided by Zhuo’s having indicated Q can have varying alkyl chain lengths, a PHOSITA would have arrived at, for example, instantly claimed Compound 11, which would inherently be a RIPK1 kinase inhibitor.
Conclusion
Claims 14, 22-27, and 30 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BRIANNA L BAUER whose telephone number is (571)272-5752. The examiner can normally be reached 8am-5pm.
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, ADAM C MILLIGAN can be reached at (571)270-7674. 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.
/B.L.B./Examiner, Art Unit 1623
/CLINTON A BROOKS/Supervisory Patent Examiner, Art Unit 1621
Prosecution Insights