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 .
DETAILED ACTION
Response to Amendment
Acknowledgment is made of the receipt and entry of the amendment filed on 01/28/2026, wherein claim 1 is amended, claims 6-15 and 20-21 are cancelled, and new claims 28-34 directed to non-elected species are added.
Election/Restriction
Applicant elected without traverse of Group I, drawn to a compound of formula II-d or pharmaceutically acceptable salt, and of the species, compound III-66 of claim 18 ( [0260], [0434] of instant specification) having following structure, in the reply filed on 06/17/2025.
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The elected species, compound III-66 (CAS # 2943933-35-3, entered STN on 14 Jul 2023 , see STN search note ). The examiner has expanded the search to non-elected bifunctional compound species wherein PTM binding moiety
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is
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and LLM is
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. The elected species and non-elected species are rejected under following 103 rejection. Other non-elected species are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected species. It should be noted that the prior art search will not be extended unnecessarily to cover all non-elected species.
Status of Claims
Claims 1-5, 16-19, 22-24 and 28-34 are pending in the instant application.
Claim 5, 17, 24, and 28-34 remain withdrawn, being drawn to nonelected species.
Claims 1-4, 16, 18, 19, 22, and 23 are currently under examination in this office action.
Response to Arguments
Applicant's remarks filed 01/28/2026 have been fully considered. Any objection and rejection found in the previous Office Action and not repeated herein has been withdrawn in view of amendment and Applicant’s remarks .The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Applicant’s argument about foreign priority is persuasive. Thus, the priority date of compound III-38 and other compounds first disclosed in PCT/CN2022/141624 have the effective filing date of 12/23/2022. For subject matters that were disclosed in CN202111634357.1, the effective filing date is considered as 12/23/2021.
Applicant argument regarding the rejections under 35USC§ 103 on the record is fully considered, but NOT persuasive. Applicant argues about lead compound analysis directed to difference of linking moiety of cited prior art compound species and “A Person of Skill in the Art Could Not Have Had A Reasonable Expectation Of Obtaining The Claimed Compositions With the Specified Lipids”.
Applicant argues ”There Is No Basis For Selecting Feng '655 Compounds, Mainolfi '465 Compounds, or Mainolfi '499 Compounds As A Starting Point For Further Modification” and further argues lack of specific teaching of cited prior art compounds (Remarks page 19-22).
RESPONSE: Applicant’s argument about lack of teachings of specific cited compounds are NOT persuasive. Please note the cited prior art compound species and linker moieties thereof are only exemplary. Not all prior art compounds comprising same linker moiety are cited and compounds comprising homologous linker and/or linker moiety with very close similarity from prior art are not listed either.
As MPEP 2143 (Example 10) states: “It should be noted that the lead compound cases do not stand for the proposition that identification of a single lead compound is necessary in every obviousness rejection of a chemical compound. For example, one might envision a suggestion in the prior art to formulate a compound having certain structurally defined moieties, or moieties with certain properties. If a person of ordinary skill would have known how to synthesize such a compound, and the structural and/or functional result could reasonably have been predicted, then a prima facie case of obviousness of the claimed chemical compound might exist even without identification of a particular lead compound”.
In instant case, the difference of instant claimed compound of Formula II-d and prior art compounds are the linker moiety. Instant claimed linker moiety
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is combination of L0, L1 , Cy and L2. Feng’ 655, Mainolfi’ 465 and Mainolfi’ 499 teach a variety of linker moiety comprising Cya , L2, and combination thereof that are similar to instant claimed linker moiety. A skilled artisan would have known to combine different linker moieties and synthesize bifunctional compounds comprising the linker moiety based on the teachings of prior art. For example, Mainolfi’ 465 and Mainolfi’ 499 teach amide linker moiety wherein Mainolfi’ 499
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read on L2 of instant elected species,
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read on Cya of instant elected species. The combination of Mainolfi’ 499 linker 560 (or 561) and 509 would have provided linker moiety that read on instant amended linker moiety of Formula IId,
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Applicant argues “There Is No Basis For Modifying Feng '655 Compounds, Mainolfi '465 Compounds, or Mainolfi '499 Compounds With The Specific Linkers Of The Instant Claims,,, the Office has improperly relied on hindsight to cobble together the necessary linker elements to arrive at the instantly claimed compounds.”(Remarks, page 23).
RESPONSE: In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
Please note instant claim 1 is directed to compound of Formula II-d genus comprising vast variety of compound species. A skilled artisan would have known to combine the linker moieties and synthesize bifunctional compounds comprising the linker moiety based on the teachings of prior art and reasonably expected the bifunctional compounds exhibit IRAK PROTAC activities. The examiner agrees that linker moiety might have impact on the IRAK4 degradation activity(Remarks, page 23). It’s well-known in pharmaceutical industry that the efficacy/activity of compound is unpredictable due to many variables and factors. Instant claims 1-4, 16, 22, and 23 are directed to compound genus/subgenus of Formula IId comprising variety of compound species that are unpredictable to exhibit improved IRAK4/unexpected result compared with prior art compounds. Thus, 35 U.S.C.103 rejection of claims 1-4, 16, 22, and 23 are maintained and made Final.
Applicant’s argument regarding double patenting rejections are NOT persuasive. It’s noted instant claim 18 and 19 still recite compound III-38, III-45 and III-66, etc. which were already claimed in the parent patent 12281098 B2. Although the scope of reference claims might be different, the compound species taught by reference claims still anticipate instant claims.
Priority
This instant application 19/086,136 filed 03/21/2025 is a continuation application of U.S. patent application No. 18/632,351 filed on April 11, 2024 (now is US patent 12281098), which is a Continuation-in-part Application of International Application No. PCT/CN2022/141624, filed on December 23, 2022, which claims the right of the priority of Chinese patent application No. 202111634357.1 filed on December 23, 2021.
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). It’s noted instant specification discloses about 73 compounds (See Table 2) while foreign application CN 202111634357.1 only discloses 37 compound or less (III-1 to III-37), the elected species, compound III-66 is not disclosed in CN 202111634357.1. Compound III-66 is disclosed in PCT/CN2022/141624 (See WO 2023/116920 A1). As such, the priority date of compounds III-38 to III-73 including the elected compound III-66 are determined to be 12/23/2022, the filing date of PCT/CN 2022/141624.
Specification
Instant specification discloses compounds with complex structures and names. The lengthy specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification.
Claim Rejections - 35 USC § 112
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.
Claim 2 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 1 is amended to recite R1 is unsubstituted pyridyl or substituted with R1-1. Claim 2 recites R1 is pyridyl which fails to further limit R1 group.
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
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.
Claims 1-4, 16, 18, 19, 22, and 23 are rejected under 35 U.S.C. 103 as being unpatentable over Feng et al. (US 20230192655, “Feng’ 655”, Applicant’s IDS dated 06/17/2025 under “US Patent Application Publication”, Cite No. A3, family member of WO 2022/088551), in view of Mainolfi et al. (WO 2022/147465, hereafter “Mainolfi’ 465”, Applicant’s IDS dated 06/17/2025, under “Foreign Patent Document”, Cite No. B3), and Mainolfi et al. (WO 2020264499, hereafter “Mainolfi’ 499”, Applicant’s IDS dated 06/17/2025, under “Foreign Patent Document”, Cite No. B4).
Feng’655 teaches bifunctional indazole compound of formula I, II, or pharmaceutical acceptable salt thereof , targeting at IRAK4 kinase protein for degradation, preparation of aforementioned indazole compounds, pharmaceutical composition comprising aforementioned IRAK4 modulators and the use thereof in the treatment or prevention of IRAK4-mediated disease or condition driven by MyD88 (See abstract, [0007]-[0028], [0111]- [0119], claims 1-15).
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Feng’ 655 indazole moiety wherein Ring A is 6-membered aryl or 5-6 membered
heteroaryl read on instantly claimed five-membered-fused six-membered compound
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Regarding the instantly claimed linker moiety,
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, Feng’ 655 teaches ring C is optionally substituted 6-10 membered aryl, 5-10-membered heteroaryl, C3-C12 cycloalkyl or 3-12-membered heterocycloalkyl containing 1-2 heteroatoms selected from N, O, or S, e.g.
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( See [0034]-[0035], claim 5) (which reads on instantly claimed Cya). Feng’ 655 teaches a variety of linker moiety and combination thereof
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(See [0021]-[0035], [0049]-[ 0051], claims 5, 13-14). Please refer to Feng’ 655 for the complete list of linker moiety that read on instant claimed linker moiety.
Feng’ 655 teaches compound species (See [0110], Examples 1-15, claim 15) that are claims or very similar to the instantly claimed compound species, for example,
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It’s noted Feng’ 655 Example 3 (See [0320]) is very similar to instant compound III-39 of claim 18 except the piperidine ring in the linker moiety. Please refer to Feng’ 655 for complete list of compound species that read on the IRAK4 moiety, linker moiety and LLM moieties respectively.
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Feng ’655 collectively teaches indazole derivatives comprising IRAK4 binding moiety, linker and LLM moiety that read on the core structure of instantly claimed five-membered-fused six-membered compound of formula IId and compound species that are very similar to instantly claimed compounds. Feng ’655 teaches IRAK4 kinase activity assay and pharmacokinetic study wherein the compounds species show good selectivity, has less toxic and side effects ( See [0387]-[0398], Table 1-4). Feng ’655 teaches pharmaceutical composition comprising compound of formula I and pharmaceutical acceptable carrier in the treatment or prevention of IRAK4-mediated disease or condition driven by MyD88.
The difference of Feng ’655 and instant claimed Formula IId is L0 ((CH2)mX)q wherein q is 1-6 directly attached to indazole IRAK4 binding moiety.
Mainolfi’ 465 teaches bifunctional compound of formula I, or pharmaceutical acceptable salt thereof, as IRAK4 degrader, comprising an Interleukin-1 receptor-associated kinases (IRAK) binding moiety, a degradation inducing moiety (DIM) and linker moiety, pharmaceutical composition comprising aforementioned bifunctional compound, and method of treating an IRAK-mediated disorder/disease with aforementioned bifunctional compounds (See abstract, [0009]- [0010], [0040]-[0090], [00496], Table 1, Examples, claims 1-19).
Regarding the instantly claimed five-membered-fused six-membered compound of Formula II, Mainolfi’ 465 teaches embodiments comprising a variety of IRAK4 binding moiety, for example, I-d-3, I-j-3 (See [0085], [0090], claims 2, 7, 9).
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Regarding instant linker moiety,
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, Mainolfi’ 465 teaches a variety of bivalent linker moiety that connects IRAK to DIM , wherein L is a covalent bond (i.e. absent), or a bivalent, saturated or unsaturated, straight or branched hydrocarbon chain, wherein 0-6 methylene units of L are independently replaced by optionally substituted Cy, or
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,etc. Please refer to Mainolfi’ 465 ([00471]-[00475], [00491]-[00493] ) for the complete list of linker moiety or combination thereof that read on instant linker moiety.
Mainolfi’ 465 teaches compound species (e. g. I-343, I-345, See [00496], Table 1 starting page 265) that are similar to the instantly compound of Formula IId wherein L0 is (CH2)mX . Please refer to Table 1 of Mainolfi’ 465 for the complete list of compound species that read on the IRAK4 moiety , linker moiety and DIM moiety respectively.
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Mainolfi’ 465 collectively teaches the core structure of instantly claimed five-membered-fused six-membered compound of formula IId( IRAK, linker and LLM moiety, etc.), and compounds species that are very similar to instantly claimed compound of Formula IId wherein L0 is (CH2)mX. Mainolfi’ 465 teaches preparation of compound species (See Examples 1-22). Mainolfi’ 465 teaches pharmaceutical composition comprising compound of formula I and pharmaceutical acceptable carrier(See [00521], claim 17).
Mainolfi’ 499 teaches bifunctional compound of formula I,
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, or pharmaceutical acceptable salt thereof, as IRAK kinase modulators, comprising an Interleukin receptor-associated kinases (IRAK) binding moiety, a degradation inducing moiety (DIM) and linker moiety, and methods of using aforementioned bifunctional compounds for treatment or amelioration of a disease condition associated with IRAK kinase (e.g. cancer, multiple myeloma, etc.) (See abstract, [0009]-[0015], claims 1-26).
Regarding the instantly claimed five-membered-fused six-membered compound of Formula IId, Mainolfi’ 499 teaches embodiments comprising a variety of IRAK4 binding moiety, for example, I-d-3 (See [0025], [0052]-[0096], [00432]- [00590], claim 2).
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Mainolfi’ 499 teaches DIM is a ligase binding moiety (LBM), cereblon E3 ubiquitin ligase binding moiety, for example, I-aa, I-zz-4, I-j-3, etc. (See Table A, [00230], claims 3, 4, 9-10) (which read on instantly claimed LLM, please refer to Table A of Mainolfi’ 499 for complete linker species that read on instant LLM moiety).
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Regarding instant linker moiety,
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, Mainolfi’ 499 teaches a variety of bivalent linker moiety that connects IRAK to DIM/LBM, wherein L is a covalent bond (i.e. absent), or a bivalent, saturated or unsaturated, straight or branched hydrocarbon chain, wherein 0-6 methylene units of L are independently replaced by substituted Cy, or
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Please refer to Mainolfi’ 499 ([00419]-[00423], [00617] , Table B, etc. ) for the complete list of linker moiety or combination thereof that read on instant linker moiety. It’ noted the linker Mainolfi’ 499 moiety
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explicitly read on L2 of instant elected species,
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read on L0 is CH2 and Cya of instant elected species.
Mainolfi’ 499 teaches compound species, e.g. I-44, I-77, I-79, I-87, I-220 , I-295, etc. (See [00619], Table 1 starting at page 365) that are similar to the instantly claimed compound species. Please refer to Mainolfi’ 499 Table 1 for the complete list of compound species that read on the IRAK4 , linker and DIM moieties, respectively).
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Mainolfi’ 499 compound species (e.g. I-79, I-87, etc.) comprising moiety
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read on instant claimed Formula IId, wherein,
R1 is optionally substituted pyridyl (e.g.
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R2 is hydrogen;
R3 is hydrogen, unsubstituted optionally substituted C1-C6 alkoxy (e.g. OMe), optionally substituted C1-C6 alkyl (e.g.
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);
L0 is CH2CH2, L1 is absent;
LLM is
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Mainolfi’ 499 teaches preparation of compound species that are very similar to instantly claimed formula IId (See Schemes 1-8, Examples), and IRAK4-mediated activities thereof (See [0012], [00663], [003576], Table 10). Mainolfi’ 499 collectively teaches the core structure of the instantly claimed five-membered-fused six-membered compound of formula IId( IRAK, linker and LLM moiety, etc.), and compounds species that very similar to instantly claimed compound. Mainolfi’ 499 teaches pharmaceutical composition comprising compound of formula II and pharmaceutical acceptable carrier (See abstract, [0002])(which reads on instant claim 22-23).
According to MPEP § 2144.09, a prima facie case of obviousness may be made when chemical compounds have very close structural similarities and 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).
Feng’ 655, Mainolfi’ 465 and Mainolfi’ 499 teach bifunctional compound, or pharmaceutical acceptable salt thereof as IRAK kinase degrader/modulator, comprising an Interleukin receptor-associated kinases (IRAK) binding moiety, ligand which binds to the E3 ubiquitin ligase (CLM/LBM) that read on instant five-membered fused six-membered IRAK binding moiety , e.g.
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and ubiquitin ligase binding moiety
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. Feng’ 655, Mainolfi’ 465 and Mainolfi’ 499 teach a variety of linker moiety and combination thereof that are similar to instant claimed linker moiety. The difference between prior art and instant claimed invention are slight difference at combination of linker moiety.
It would have been obvious to one of ordinary skill in the art to further explore more linker moiety and combination thereof for SAR study of IRAK4 modulator, based on combined teachings of Feng’ 655, Mainolfi’ 465, Mainolfi’ 499, and experimentation/optimization based on general knowledge of structure similarity and bioisosteric modification, and arrive at instantly claimed invention with reasonable expected success. For example, Feng’ 655 teaches Example 13,
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Mainolfi’ 499 teaches compound 220 that are very similar to instantly elected species, compound III-66 except slight difference at the linker moiety in absence of (CH2)m and CO bond,
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Mainolfi’ 499 already teach a variety of linker moiety with (CH2)m and CO bond, e.g.
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. The exploration of linker moiety and combination thereof based on the combined teachings of prior art, such as incorporating (CH2)m and other linker moiety as taught by Mainolfi’ 465 and Mainolfi’ 499, would provide alternative bifunctional IRAK modulator that read on the elected species and other non-elected species.
The skilled artisan would be motivated to further explore linker moiety for SAR study of IRAK inhibitors based on combined teachings of prior art, because all teachings are directed to bifunctional compounds having similar five-membered fused six-membered IRAK binding moiety and ubiquitin ligase binding moiety. The SAR study of linker moiety based on the combined teachings of prior art, together with further modification/ optimization based on general knowledge of structure similarity and bioisosteric modification would provide more alternative bifunctional compounds that are reasonably expected to exhibit IRAK modulating activity. One of ordinary skill in the art would have had reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole is prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, as evidenced by the references, especially in the absence of evidence to the contrary.
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 1-4, 16, 18, 19, 22, and 23 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 of US 12281098 B2.
Reference claim 1-3 are directed to five-membered-fused six-membered bifunctional compound or a pharmaceutically acceptable salt thereof, including instant elected species, compound III-66, and other non-elected species, III-38, III-45, etc. that are encompassed by instant compound of Formula IId. Reference claim 3 is directed to compound III-38 which is also recited in instant claims 18 and 19. It’s noted the structures in claims 1 of published US12281098B2 are truncated/fragmented due to printer error. Please refer to Table 1 of US12281098B2 for the correct structure of compounds III-66, III-38, III-45, etc.
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Instant application is a continuation of US12281098B2 and no 35 USC 121 shield exists. Thus, reference claims anticipate instant claims.
Claim 1-4, 16, 18, 19, 22, and 23 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 of US12343343B2 ( U.S. application No.18/651,214), in view of Mainolfi et al. (WO 2020264499, Mainolfi’ 499).
Reference claims are directed to bifunctional compounds of formula I-1, a pharmaceutically acceptable salt or an isotope thereof, and a pharmaceutical composition comprising formula I-1 and pharmaceutical excipients.
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Reference compound Formula I-1 comprises the same Interleukin receptor-associated kinases (IRAK) binding moiety , LLM moiety and similar linker groups as instant claims.
According to MPEP § 2144.09, A prima facie case of obviousness may be made when chemical compounds have very close structural similarities and 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).
The collective teachings of Mainolfi’ 499 are elaborated in preceding 103 rejection. Mainolfi’ 499 collectively teaches bifunctional compound as IRAK kinase modulator that are very similar to instantly claimed compound of formula IId( IRAK, linker and LLM moiety, etc.). Mainolfi’ 499 teaches variety of linker moiety with (CH2)m and CO bond, e.g.
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It would have been obvious to one of ordinary skill in the art to further explore more linker moiety and combination thereof for SAR study of IRAK4 bifunctional/PROTAC modulator, based on combined teachings of reference claims and Mainolfi’ 499, together with experimentation/optimization based on general knowledge of structure similarity and bioisosteric modification.
The instant application shares at least one common inventor /applicant with the reference patent application. Furthermore, the instant application is not related to the reference patent based on the record, thus no 35 USC 121 shield exists.
Claim 1-4, 16, 18, 19, 22, and 23 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of copending U.S. application No. 19/189,146 (reference application, NOA mailed on 01/14/2026), in view of Mainolfi et al. (WO 2020264499, Mainolfi’ 499). This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Reference claims are directed to bifunctional compound comprising the same Interleukin receptor-associated kinases (IRAK) binding moiety and LLM moiety, and similar linker groups as instant compound of Formula IId, or a pharmaceutically acceptable salt thereof and a pharmaceutical composition comprising aforementioned bifunctional compounds. For example,
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The difference between reference compounds and instant claimed invention are slight difference at combination of linker moiety. According to MPEP § 2144.09, A prima facie case of obviousness may be made when chemical compounds have very close structural similarities and 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).
The collective teachings of Mainolfi’ 499 are elaborated in preceding 103 rejection. Mainolfi’ 499 collectively teaches bifunctional compound as IRAK kinase modulator that are very similar to instantly claimed compound of formula IId( IRAK, linker and LLM moiety, etc.). Mainolfi’ 499 teaches variety of linker moiety with (CH2)m and CO bond, e.g.
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It would have been obvious to one of ordinary skill in the art to further explore more linker moiety and combination thereof for SAR study of IRAK4 bifunctional/PROTAC modulator, based on combined teachings of reference claims and Mainolfi’ 499, together with experimentation/optimization based on general knowledge of structure similarity and bioisosteric modification.
The instant application shares at least one common inventor /applicant with the reference patent application. Furthermore, the instant application is not related to the reference application based on the record, thus no 35 USC 121 shield exists.
Conclusion
No claim is 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LIYUAN MOU whose telephone number is (571)270-1791. The examiner can normally be reached Mon-Fri 9:00-5:30.
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/LIYUAN MOU/Examiner, Art Unit 1628
/JARED BARSKY/Primary Examiner, Art Unit 1628