DETAILED ACTION
All rejections and objections not mentioned below have been withdrawn.
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 .
Election/Restrictions
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Applicant’s election without traverse of compound WX001 (shown below), in the reply filed on 08/27/2025 is acknowledged.
Claims 1, 11, 13, and 17-20 read on the elected species.
In light of this species election, a search of compound WX001 was conducted. The compound WX001 was found free of the art. The scope was expanded to the second compound of claim 19 (shown below).
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Priority
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). The certified copy has been filed in parent Application No. CN202010187846.6, filed on 03/17/2020.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 12/07/2022, 05/30/2023, 02/13/2024 are being considered by the examiner.
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.
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, 11, 13, and 17-20 is/are rejected under 35 U.S.C. 103 as being unpatentable over CREWS (CREWS et al., US 20170121321 A1, 2017) in view of LUO (LUO et al., WO2020048546A1, 2020-03-12, IDS) further in view of LIU (LIU et al., US 12410171 B2 effective filing date 2020-02-26).
The reference CREWS teaches “The invention provides a compound of formula (I). The invention further provides a pharmaceutical composition comprising at least one compound of formula (I) and at least one pharmaceutically acceptable carrier. The invention further provides a method of treating or preventing a disease or disorder associated with overexpression and/or uncontrolled activation of c-Abl and/or BCR-ABL. The invention further provides a method of preventing or treating a tyrosine kinase-dependent cancer in a subject in need thereof. In certain embodiments, the compound of formula (I) is TKI-L-(ULM)k (I), wherein: TKI is a tyrosine kinase inhibitor, L is a linker, each ULM is independently a ubiquitin ligase binder, and k is an integer ranging from 1 to 4, wherein TKI is covalently linked to L and wherein each ULM is covalently linked to L; or a salt, enantiomer, stereoisomer, solvate, polymorph or N-oxide thereof”[0006-0007]. The reference CREWS teaches (reference claim 1 and 9):
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“The compound of claim 1, wherein the TKI is at least one selected from the group consisting of Dasatinib, Imatinib, Saracatinib, Ponatinib, Nilotinib, Danusertib, AT9283, Degrasyn, Bafetinib, KW-2449, NVP-BHG712, DCC-2036, GZD824, GNF-2, PD173955, GNF-5, Bosutinib, Gefitinib, Erlotinib, Sunitinib, Ruxolitinib, Tofacitinib, Lapatinib, Vandetanib, Sorafenib, Sunitinib, Axitinib, Nintedanib, Regorafenib, Pazopanib, Lenvatinib, Crizotinib, Ceritinib…”(reference claim 9). This helps to teach claims 1, 11, 13, and 17-20.
The reference Crew does not teach the correct linker or ULM (claims 1, 11, 13, and 17-20 ).
The reference LUO teaches “Thalidomide, trade name is reaction stop, was first synthesized by the German company Grande. During the second half of the 1950s to the early 1960s, it was sold as a sedative in more than 40 countries and widely used as an antiemetic for pregnant women, eventually resulting in the tragedy of tens of thousands of infants with seal limb deformity (morphogenesis disorder). And withdraw from the market.
Since the "reaction stop" incident, the teratogenic mechanism of thalidomide has aroused great interest of researchers. The protein Cereblon (CRBN) has been proven to be a target protein for thalidomide teratogenic effects. Thalidomide binds CRBN, DNA damage binding protein DDB1 (Damaged DNA Protein 1), CUL4A (Cullin-4A), and Cullins 1 regulator (ROC1) to form an E3 ubiquitin ligase complex, which binds a variety of substrates The protein is ubiquitinated to form a ubiquitinated chain, so that the substrate protein is recognized and hydrolyzed by the proteasome. Diamines are called immunomodulatory drugs (IMiDs). They activate the ubiquitination of the transcription factors IKZF1 and IKZF3 by the E3 ubiquitin ligase complex formed with CRBN, and are recognized and degraded by the proteasome. Multiple myeloma (Multiple Myeloma) produces toxic effects. The absence of these two transcription factors stops the growth of myeloma. Doxamine drugs such as lenalidomide and pomalidomide are first-line drugs for the treatment of multiple myeloma.
CRBN is a 442 amino acid protein that is conserved from plant to human. It is located on the short arm of p26.3 of human chromosome 3 and has a molecular weight of 51 kDa. In humans, the CRBN gene has been identified as a candidate gene for autosomal recessive non-syndrome mild mental retardation (ARNSMR). CRBN is widely expressed in testes, spleen, prostate, liver, pancreas, placenta, kidney, lung, skeletal muscle, ovary, small intestine, peripheral blood leukocytes, colon, brain, and retina, but in brain tissue (including retina) and testes The expression was significantly higher in other tissues.
CRBN, as an important target of antitumor and immunomodulator drugs, has been proven in multiple hematological malignancies such as multiple myeloma, chronic lymphocytic leukemia, skin diseases such as leprosy nodular erythema, and systemic lupus erythematosus. Autoimmune diseases have a clear effect. Doxamines have more side effects, especially peripheral neuropathy. There is an urgent need to develop CRBN modulator drugs without teratogenic effects, fewer peripheral neuropathies, stronger immunomodulatory effects, and higher antitumor activity to improve clinical treatment effects, reduce clinical side effects, and facilitate long-term use of patients”[Background technique].The reference LUO also teaches the following ULM (claim 1 and claim 11), wherein R1=alkyl groups. This helps to teach claims 1, 11, 13, and 17-20.
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The reference LIU teaches the following lead compound with the correct linker (column 1520) as well as bivalent compounds comprising kinase ligands conjugated to a degradation tag via a linker(page 12-13). This helps to teach claims 1, 11, 13, and 17-20.
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It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant invention to have modified CREWS’ TKI-L-(ULM) compound with LUO ULM because they both teach ULM for the same purpose of degrading a target protein. One would be motivated to do so with reasonable expectation of success because it is obvious to substitute known equivalents for the same purpose. LUO also provides the motivation that its ULM is superior over Thalidomide. It would have been obvious to modify CREW, LUO with the linker of LIU also because one would be motivated to do so with reasonable expectation of success because it is obvious to substitute known equivalents for the same purpose.
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, 11, 13, and 17-20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8, 11-19, 23-24 of copending Application No. 19/107,901 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because generic to a species or sub-genus claimed in a conflicting patent or application, i.e., the entire scope of the reference claim falls within the scope of the examined claim.
The application ‘901 claims:
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Wherein, E=bond, X=furyl, Y=Z=phenyl. This anticipates claims 1-2, 9-11, 14, 17, 18, 20.
Claims 1, 11, 13, and 17-20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of copending Application No. 19/164,227 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because generic to a species or sub-genus claimed in a conflicting patent or application, i.e., the entire scope of the reference claim falls within the scope of the examined claim.
The application ‘227 claims:
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Wherein, E=NH, X= isoxazolyl, Y=Z=phenyl. This anticipates claims 1-2, 10-11, 14, 18, 20.
Claims 1, 11, 13, and 17-20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-43 of copending Application No. 19/164,229 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because generic to a species or sub-genus claimed in a conflicting patent or application, i.e., the entire scope of the reference claim falls within the scope of the examined claim.
The application ‘229 claims:
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Wherein, E=NH, X= isoxazolyl, Y=Z=phenyl. This anticipates claims 1-2, 10-11, 14, 18, 20.
Claims 1, 11, 13, and 17-20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of copending Application No. 18/689,074 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because generic to a species or sub-genus claimed in a conflicting patent or application, i.e., the entire scope of the reference claim falls within the scope of the examined claim.
The application ‘074 claims:
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Wherein, E=NH, X= furyl, Y=Z=phenyl. This anticipates claims 1-4, 9-11, 14, 18, 20.
Claims 1, 11, 13, and 17-20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of copending Application No. 18/695,174 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because generic to a species or sub-genus claimed in a conflicting patent or application, i.e., the entire scope of the reference claim falls within the scope of the examined claim.
The application ‘174 claims:
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Wherein, E=NH, X= furyl, Y=Z=phenyl. This anticipates claims 1-4, 9-11, 14, 18, 20.
Claims 1, 11, 13, and 17-20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of copending Application No. 18/549,186 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because generic to a species or sub-genus claimed in a conflicting patent or application, i.e., the entire scope of the reference claim falls within the scope of the examined claim.
The application ‘186 claims:
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Wherein, E=NH, X= furyl, Y=Z=phenyl. This anticipates claims 1-4, 9-14, 17-18, 20.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Claims 1, 11, 13, and 17-20 are rejected.
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/A.A.S./ Examiner, Art Unit 1627
/Kortney L. Klinkel/ Supervisory Patent Examiner, Art Unit 1627