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
This Application is a 371 of PCT/CN2022/081544, filed Mar. 17, 2022 and claims foreign priority to PCT/CN2021/081514, filed Mar. 18, 2021 in China.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on Mar. 12, 2026 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Status – Response to Restriction/ Election Requirement
Claims 1-60 are currently pending.
Applicant’s election of Group I in the reply filed on Mar. 12, 2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)). The restriction requirement was based on unity of invention for this national stage application. The Applicant traversed on the grounds that the Application contains the same technical feature (the compound of formula (I)) and thus there is no search burden. Restriction was required on the grounds that unity was broken due to a shared technical feature which does not make a contribution over the prior art (the compound of formula (I)). The Applicant did not traverse unity of invention and thus did not distinctly and specifically point out the error in the restriction requirement.
Applicant’s election of compound 4, having the structure:
PNG
media_image1.png
222
422
media_image1.png
Greyscale
in the reply filed on Mar. 12, 2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 1-3, 12, 21-33 and 47-55 read on the elected invention and are currently active and subject to examination. Claims 4-11, 13-20, 34-46 and 56-60 are withdrawn.
Applicant is reminded that upon the cancelation of claims to a non-elected invention, the inventorship must be corrected in compliance with 37 CFR 1.48(a) if one or more of the currently named inventors is no longer an inventor of at least one claim remaining in the application. A request to correct inventorship under 37 CFR 1.48(a) must be accompanied by an application data sheet in accordance with 37 CFR 1.76 that identifies each inventor by his or her legal name and by the processing fee required under 37 CFR 1.17(i).
Claim Rejections – 35 USC § 112(b)
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 1-3, 12, 21-33, 47-53 and 55 are 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.
One of ordinary skill in the art cannot determine the metes and bounds of the compound of formula I of claim 1 because claim 1 includes contradicting definitions for the allowed members of the compound of formula I in (i) and (ii). The limitation (i) states:
PNG
media_image2.png
161
720
media_image2.png
Greyscale
Limitation (ii) states:
PNG
media_image3.png
360
744
media_image3.png
Greyscale
It is unclear what definition applies because there is a broader range or limitation followed by a narrower range or limitation.
Claims 2-3, 12, 21-33, 47-53 and 55 depend from claim 1 and do not resolve this ambiguity and are therefore also indefinite.
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(s) 1-2, 21-23, 31-33, and 47 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Zhong et al. (Supporting information, ACS Infectious Diseases, Vol. 5, No. 3, 326-335, Jan. 35, 2019) (of record, IDS July 24, 2024).
Claim 1 is directed towards a compound of formula I:
PNG
media_image4.png
151
520
media_image4.png
Greyscale
Zhong teaches a compound falling within formula I:
PNG
media_image5.png
107
326
media_image5.png
Greyscale
(Zhong, p. S19, compound 60).
As in formula I of claim 1, X is N, X1, X2 and X3 are C, Y is absent, Ra, Rb and Rc are H, Ar1 is phenyl,
PNG
media_image6.png
143
522
media_image6.png
Greyscale
, R1 is C3-alkoxy, m is 1, and n, p and q are 0.
Thus, claim 1 is anticipated.
Claims 2, 21-23, 31-33, and 47 read on the above compound 60 and are therefore also anticipated.
Claim(s) 1-3, 21-23, 31-33, 47, 49 and 55 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Marino et al. (WO2009097474A1) (of record, IDS Sept. 11, 2023, cite no. 3).
Claim 1 is directed towards a compound of formula I:
PNG
media_image4.png
151
520
media_image4.png
Greyscale
Marino teaches compounds falling within formula I. For example:
PNG
media_image7.png
128
191
media_image7.png
Greyscale
Marino, Specification, p. 34, Example 12.
PNG
media_image8.png
136
237
media_image8.png
Greyscale
Id., p. 36, Example 13.
As in formula I of claim 1, X is N, X1, X2 and X3 are C, Y is absent, Ra, Rb and Rc are H, Ar1 is phenyl,
PNG
media_image9.png
121
345
media_image9.png
Greyscale
, Ar3 is phenyl, R1 is for each occurrence, C1-alkyl or halogen, wherein the alkyl is substituted with halogen, R2 is NRpRq, p is 0, n is 1, and m is 1 or 2.
Therefore, claim 1 is anticipated.
Claims 2-3, 21-23, 31-33, 47, and 49 read on the above compound(s) and are therefore also anticipated.
Claim 55 is directed towards a pharmaceutical composition comprising a compound according to claim 1 and at least one pharmaceutically acceptable carrier. Marino teaches a pharmaceutical composition comprising the compound and at least one pharmaceutically acceptable carrier (Marino, Specification, p. 43-44).
Therefore, claim 55 is anticipated.
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.
Claim(s) 1-3, 12, 21-25, 31-33, 47-53 and 55 is/are rejected under 35 U.S.C. 103 as being unpatentable over Daugan et al. (US20190345138A1) in view of Harris (Expert Opinion on Therapeutic Patents, Vol. 31, p. 137-151, published Dec. 4, 2020) (of record, cite no. 12, IDS Mar. 12, 2026).
Claim 1 is directed towards a compound of formula I:
PNG
media_image4.png
151
520
media_image4.png
Greyscale
Daugan teaches similar RIP1 kinase inhibitors largely similar to the compound of formula I. For example:
PNG
media_image10.png
177
238
media_image10.png
Greyscale
Daugan, Specification, p. 47, ex. 4;
PNG
media_image11.png
206
277
media_image11.png
Greyscale
Id., p. 89, ex. 121;
PNG
media_image12.png
210
267
media_image12.png
Greyscale
Id., p. 101, ex. 140;
PNG
media_image13.png
197
242
media_image13.png
Greyscale
Id., p. 106, ex. 148.
These compounds have typical inhibitory activity for compounds within this class—pIC50 between 6.0 and 9.0 (Id., p. 122, paragraph [0861]), which is an IC50 value between 1 nM and 1 µM.
. Compounds 4, 140 and 148 have excellent inhibitory activity for compounds of the class— pIC50 between 8.0 and 9.0 (Id., p. 122, paragraphs [0863], [0868]), which is an IC50 value between 1 and 10 nM.
These compounds differ from formula I in that there is a dihydropyrazole instead of an open chain benzylamide. One of ordinary skill in the art would have a reasonable expectation of success to substitute an open chain benzylamide for dihydropyrazole and arrive at the compound of formula I because it is commonly known in the art that benzylamide is a bioisostere of dihydropyrazole in the binding pocket of the RIP1 receptor.
For example, Harris shows that the dihydropyrazole structure has been modified to give open chain analogs (e.g. compound 20 vs. compound 24):
PNG
media_image14.png
280
901
media_image14.png
Greyscale
Harris, Fig. 11, p. 144;
PNG
media_image15.png
444
892
media_image15.png
Greyscale
Harris, Fig. 12, p. 145.
Therefore, claim 1 was prima facie obvious at the time of filing.
Claims 2-3, 12, 21-25, 31-33, 47-48, 50, 51 and 53 read on the compounds 121, 140 and 148 as described in claim 1 above and are prima facie obvious for the reasons given in the rejection of claim 1.
Claim 49 is directed towards the compound of claim 1, wherein R1 is independently selected from F, Cl, cyano, CF3 CF2H and CH3.
One of ordinary skill in the art would have a reasonable expectation of success to develop a RIP1 inhibitor wherein R1 is independently selected from F, Cl, cyano, CF3 CF2H and CH3 because these substituents are commonly known in the art for RIP1 inhibitors.
For example, Daugan teaches similar RIP1 inhibitors wherein R1 is F:
PNG
media_image16.png
189
242
media_image16.png
Greyscale
Id., p. 70, ex. 78.
Therefore, claim 49 was prima facie obvious at the time of filing.
Claim 52 is directed towards the compound of claim 1, wherein R4 is independently selected from F and CH3.
One of ordinary skill in the art would have a reasonable expectation of success to develop a RIP1 inhibitor wherein R4 is independently selected from F, Cl, cyano, CF3 CF2H and CH3 because these substituents are commonly known in the art for RIP1 inhibitors.
For example, Harris teaches similar RIP1 inhibitors wherein R4 is F (compound 27, Fig. 12, p. 125).
Therefore, claim 52 was prima facie obvious at the time of filing.
Claim 55 is directed towards a pharmaceutical composition comprising a compound according to claim 1 and at least one pharmaceutically acceptable carrier. Daugan teaches pharmaceutical compositions comprising the RIP1 inhibitor and a pharmaceutically acceptable carrier (Daugan, Specification, paragraph [0649]). Therefore, claim 55 was prima facie obvious at the time of filing.
Claim(s) 1-3, 12, 21-33, 47-53 and 55 is/are rejected under 35 U.S.C. 103 as being unpatentable over Daugan et al. (US20190345138A1) in view of Harris (Expert Opinion on Therapeutic Patents, Vol. 31, p. 137-151, published Dec. 4, 2020), as applied to claim(s) 1-3, 12, 21-25, 31-33, 47-53 and 55 above, and further in view of Wipf (Bioisosterism, p. 43-64, Feb. 14, 2008).
The rejection of claims 1-3, 12, 21-25, 31-33, 47-53 and 55 above as obvious over Daugan in view of Harris is incorporated herein by reference.
Claims 26-30 are directed towards the compound of claim 1, wherein Ar3 is triazole. As shown in the rejection of claim 1 above, Daugan teaches a compound of claim 1 wherein Ar3 is tetrazole. While Daugan does not specifically teach a compound wherein Ar3 is triazole, one of ordinary skill in the art would have a reasonable expectation of success to substitute triazole for tetrazole because N is a known ring equivalent for CH.
For example, see the teachings of Wipf:
PNG
media_image17.png
156
731
media_image17.png
Greyscale
Wipf, p. 45.
Therefore, claims 26-30 were prima facie obvious at the time of filing.
Given the above teachings, the invention as a whole was prima facie obvious at the time of filing.
Nonstatutory Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 21-33, 47-51, 53 and 55 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-21 of copending Application No. 17/998,552 (herein the ‘552 application) in view of Harris (Expert Opinion on Therapeutic Patents, Vol. 31, p. 137-151, published Dec. 4, 2020) (of record, cite no. 12, IDS Mar. 12, 2026).
Claim 1 is directed towards a compound of formula I:
PNG
media_image4.png
151
520
media_image4.png
Greyscale
The ‘552 application claims compounds largely similar to the compounds of formula I. For example:
PNG
media_image18.png
153
194
media_image18.png
Greyscale
(‘552 application, claim 20).
These compounds differ from formula I in that there is a dihydropyrazole instead of an open chain benzylamide. One of ordinary skill in the art would have a reasonable expectation of success to substitute an open chain benzylamide for dihydropyrazole and arrive at the compound of formula I because it is commonly known in the art that benzylamide is a bioisostere of dihydropyrazole in the binding pocket of the RIP1 receptor.
For example, Harris shows that the dihydropyrazole structure has been modified to give open chain analogs:
PNG
media_image14.png
280
901
media_image14.png
Greyscale
Harris, Fig. 11, p. 144;
PNG
media_image15.png
444
892
media_image15.png
Greyscale
Harris, Fig. 12, p. 145.
Therefore, claim 1 is provisionally rejected on the ground of nonstatutory double patenting.
Claims 21-33, 47-51, and 53 read on the above compound 1 and are provisionally rejected on the same grounds as claim 1.
Claim 55 is directed towards a pharmaceutical composition comprising the compound as is claim 21 of the ‘552 application.
This is a provisional nonstatutory double patenting rejection.
Claims 1-3, 12, 21-33 and 47-55 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-28 of U.S. Patent No. 12,454,529 (herein “the ‘549 patent”) in view of Harris (Expert Opinion on Therapeutic Patents, Vol. 31, p. 137-151, published Dec. 4, 2020) (of record, cite no. 12, IDS Mar. 12, 2026).
Claim 1 is directed towards a compound of formula I:
PNG
media_image4.png
151
520
media_image4.png
Greyscale
.
For example, claim 55 is directed towards the following compound of formula I of claim 1:
.
PNG
media_image19.png
89
181
media_image19.png
Greyscale
(instant claim 55).
The ‘529 patent claims largely similar compounds. For example:
PNG
media_image20.png
143
195
media_image20.png
Greyscale
(‘529, claim 26).
This compound differs from instantly claimed compound 4 in two aspects. First in that there is a dihydropyrazole instead of an open chain benzylamide. Second in that X3 is N vs. C.
One of ordinary skill in the art would have a reasonable expectation of success to substitute an open chain benzylamide for dihydropyrazole and C for N for X3 and arrive at the compound of formula I because it is commonly known in the art that benzylamide is a bioisostere of dihydropyrazole in the binding pocket of the RIP1 receptor as well as that X3 is C in most RIP1 inhibitors.
For example, Harris shows that the dihydropyrazole structure has been modified to give open chain analogs and that X3 is C in known RIP1 inhibitors:
PNG
media_image14.png
280
901
media_image14.png
Greyscale
Harris, Fig. 11, p. 144;
PNG
media_image15.png
444
892
media_image15.png
Greyscale
Harris, Fig. 12, p. 145.
Therefore, claim 1 is rejected on the ground of nonstatutory double patenting.
Claims 2-3, 12, 21-33, 47-51 and 53-54 read on the above compounds and are therefore prima facie obvious and rejected on the ground of nonstatutory double patenting for the reasons given in the rejection of claim 1.
Claim 52 is directed towards the compound of claim 1, wherein R4 is F. While the ‘529 patent does not claim a compound wherein R4 is F, one of ordinary skill in the art would have a reasonable expectation of success to obtain a RIP1 inhibitor wherein R4 is F because such RIP1 inhibitors are commonly known in the art. For example, see compound 27 of Harris above (Harris, Fig. 12, p. 145).
Claim 55 of the instant application claims a pharmaceutical composition like claim 27 of the ‘529 application and is therefore rejected on the ground of nonstatutory double patenting.
Given the above teachings, the invention as a whole is unpatentable over the claims of the ‘529 patent in view of Harris.
Claims 1, 21-33, 47-51, 53 and 55 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-43 of copending Application No. 18/561,308 (herein the ‘308 application) in view of Harris (Expert Opinion on Therapeutic Patents, Vol. 31, p. 137-151, published Dec. 4, 2020) (of record, cite no. 12, IDS Mar. 12, 2026). While the claims at issue are not identical they are not patentably distinct because the ‘308 application claims compounds largely similar to formula I. For example:
PNG
media_image21.png
134
167
media_image21.png
Greyscale
(‘308 application, claim 37). The compounds of the ‘308 application are nearly identical to and comparable to the compounds of the ‘552 application for the purposes of the rejection. Claims 1, 21-33, 47-51, and 53 are provisionally rejected on the same grounds as given in the provisional rejection of these claims over the ‘552 application, incorporated herein by reference.
Claim 38 of the ‘308 application claims a pharmaceutical composition as does claim 55 of the instant application and claim 55 is therefore provisionally rejected on the ground of nonstatutory double patenting.
Conclusion
No claim is found to be allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to HEATHER DAHLIN whose telephone number is (571)270-0436. The examiner can normally be reached 9-5.
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, Jeffrey Lundgren can be reached on (571) 272-5541. 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 86-217-9197 (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.
/HEATHER DAHLIN/Examiner, Art Unit 1629
Prosecution Insights