DETAILED ACTION
Status of Claims
The amendment submitted October 10, 2025 has been entered.
Claims 1-4, 6, 8, 10, 11, 14, 15, 19, 21, 24-26, and 51-53 are pending and under consideration.
Claims 5, 7,9, 12-13, 16-18, 20, 22-23, 27-50, and 54-55 are cancelled by Applicant.
Claim 53 is withdrawn as explained below in the Election/Restriction section.
Claims 1-4, 6, 8, 10, 11, 14, 15, 19, 21, 24-26, and 51-52 are under consideration in the instant office action as explained below in the Election/Restriction section
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 National Phase Application of PCT/CN2021/123935 filed October 14, 2021, which claims the benefit of priority to PCT/CN2020/120945 filed October 14, 2020. Acknowledgment is made of applicant's claim for foreign priority based on an application filed in China on October 14, 2020. It is noted, however, that applicant has not filed a certified copy of the PCT/CN2020/120945 application as required by 37 CFR 1.55. As indicated in the filing receipt dated August 29, 2023, no access code has been provided.
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-4, 6, 8, 10, 11, 14, 15, 19, 21, 24-26 and 51-52, drawn to a compound of the Formula recited in claim 1 in the reply filed on October 10, 2025 is acknowledged.
Applicant’s election without traverse of Example 1 as a species of a compound of formula (I) and leukemia as a species of cancer in the reply filed on October 10, 2025 is likewise acknowledged.
Example 1
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Example 1 was found free of prior art; therefore, for the purposes of compact prosecution the search was expanded.
Claim 53 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on October 10, 2025.
Claims 1-4, 6, 8, 10, 11, 14, 15, 19, 21, 24-26 and 51-52 are under consideration and the subject of this Office Action.
Information Disclosure Statement
Two information disclosure statements (IDS) submitted on September 4, 2024 and July 11, 2023 are acknowledged. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Specification
Abstract Objections
Applicant is reminded of the proper content of an abstract of the disclosure.
A patent abstract is a concise statement of the technical disclosure of the patent and should include that which is new in the art to which the invention pertains. The abstract should not refer to purported merits or speculative applications of the invention and should not compare the invention with the prior art.
If the patent is of a basic nature, the entire technical disclosure may be new in the art, and the abstract should be directed to the entire disclosure. If the patent is in the nature of an improvement in an old apparatus, process, product, or composition, the abstract should include the technical disclosure of the improvement. The abstract should also mention by way of example any preferred modifications or alternatives.
Where applicable, the abstract should include the following: (1) if a machine or apparatus, its organization and operation; (2) if an article, its method of making; (3) if a chemical compound, its identity and use; (4) if a mixture, its ingredients; (5) if a process, the steps.
Extensive mechanical and design details of an apparatus should not be included in the abstract. The abstract should be in narrative form and generally limited to a single paragraph within the range of 50 to 150 words in length.
See MPEP § 608.01(b) for guidelines for the preparation of patent abstracts.
The abstract of the disclosure is objected to because the abstract is less than 50 words. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
Disclosure Objections
The disclosure is objected to because of the following informalities: On page 38-49, Table 1, the structures are too small and difficult to read.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-4, 6, 8, 10, 11, 14, 15, 19, 21, 24-26, and 52 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
In claim 1, Applicant recites compounds containing H, where H is an HSP90, KRAS or ERK5 binder; L is a linker; and T is a target protein binder.
At page 3 of Applicant’s specification, Applicant has defined H as “a chemical moiety capable of binding a target protein or proteins; 2) a chemical moiety capable of binding a chaperone protein or proteins or component of chaperone complex (e.g., HSP90, KRAS, MAPK7); and 3) a chemical moiety (linker) that joins the other two other moieties.”
On page 6, Applicant defines the following: “The term "KRAS" refers collectively, individually or in various combinations to the protein product of the wild type or mutated KRAS proto-oncogene, GTPase gene. The term "HSP70" refers collectively, individually or in various combinations to the protein products of members of the heat shock protein family A (70 kDa) gene family, including but not limited to: HSPA1A (HSP70-1), HSPA1B (HSP70-2), HSPA1L (HSP70- HOM) and HSPA8 (HSC70). The term "HSP90" refers collectively, individually or in various combinations to the protein products of members of the heat shock protein 90 (90 kDa) gene family, including: HSP90AA1 (HSP90-alpha or HSP90α), HSP90AB1 (HSP90-beta or HSP90B), HSP90B1 (GRP94) and TRAP1.”
Applicant has defined L, a linker on page 6 of Applicant’s specification as “The term "linker" or "tether," used interchangeably, refers to a chemical moiety that joins two other moieties (e.g., a first binding moiety and a second binding moiety). A linker can covalently join a first binding moiety and a second binding moiety. In one aspect, the linker is uncleavable in vivo. In one aspect, the linker comprises one or more cyclic ring systems. In another aspect, the linker comprises an alkyl chain optionally substituted by and/or interrupted with one or more chemical groups. In one aspect, the linker comprises optimal spatial and chemical properties to effectuate optimal therapeutic activity. In one aspect, the linker does not interfere with the ability of the first binding moiety and/or the second binding moiety to bind their respective targets (e.g., HSP90 and the protein(s) targeted for degradation, such as KRAS or MAPK7). In one aspect, the linker alters the ability of the first binding moiety and/or the second binding moiety to bind their respective targets (e.g., HSP90 and the protein(s) targeted for degradation, such as KRAS or MAPK7).”
Based on Applicant’s definition and specification, it is reasonable to conclude that instant invention as per claim 1 encompasses a broad class of compounds consisting of three components that are equally broad and diverse in structure and function, giving rise to various equally diverse permutations.
As per MPEP 2163 I, A: “Written description issues may also arise if the knowledge and level of skill in the art would not have permitted the ordinary artisan to immediately envisage the claimed product arising from the disclosed process. See, e.g., Fujikawa v. Wattanasin, 93 F.3d 1559, 1571, 39 USPQ2d 1895, 1905 (Fed. Cir. 1996) (a "laundry list" disclosure of every possible moiety does not necessarily constitute a written description of every species in a genus because it would not "reasonably lead" those skilled in the art to any particular species).”
To this aim, Applicant has simply provided a “laundry list” disclosure for the compounds as claimed particularly for H and T, the target protein binder components without providing sufficient written description and support for possession of the invention encompassing the broad diversity of structure and function as defined by Applicant; therefore, not enabling an ordinarily skilled artisan to envisage the claimed product or guiding the ordinarily skilled artisan to any particular species.
As per MPEP 2163 II, A, 3(a), i): “Whether the specification shows that the inventor was in possession of the claimed invention is not a single, simple determination, but rather is a factual determination reached by considering a number of factors. Factors to be considered in determining whether there is sufficient evidence of possession include the level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention.”
“In contrast, for inventions in emerging and unpredictable technologies, or for inventions characterized by factors not reasonably predictable which are known to one of ordinary skill in the art, more evidence is required to show possession…Furthermore, disclosure of a partial structure without additional characterization of the product may not be sufficient to evidence possession of the claimed invention. See, e.g., Amgen, 927 F.2d at 1206, 18 USPQ2d at 1021 ("A gene is a chemical compound, albeit a complex one, and it is well established in our law that conception of a chemical compound requires that the inventor be able to define it so as to distinguish it from other materials, and to describe how to obtain it. Conception does not occur unless one has a mental picture of the structure of the chemical, or is able to define it by its method of preparation, its physical or chemical properties, or whatever characteristics sufficiently distinguish it. It is not sufficient to define it solely by its principal biological property, e.g., encoding human erythropoietin, because an alleged conception having no more specificity than that is simply a wish to know the identity of any material with that biological property. We hold that when an inventor is unable to envision the detailed constitution of a gene so as to distinguish it from other materials, as well as a method for obtaining it, conception has not been achieved until reduction to practice has occurred, i.e., until after the gene has been isolated." (citations omitted)). In such instances the alleged conception fails not merely because the field is unpredictable or because of the general uncertainty surrounding experimental sciences, but because the conception is incomplete due to factual uncertainty that undermines the specificity of the inventor’s idea of the invention. Burroughs Wellcome Co. v. Barr Labs. Inc., 40 F.3d 1223, 1229, 32 USPQ2d 1915, 1920 (Fed. Cir. 1994). Reduction to practice in effect provides the only evidence to corroborate conception (and therefore possession) of the invention. Id.”
As presently claimed, Applicant has defined the components for compounds recited in claim by biological properties (i.e: “HSP90, KRAS, or ERK5 binder” and “target protein binder”), which is simply a wish for possession based on the lack of description and guidance for what such compounds would entail and what components an ordinarily skilled artisan would be guided to select based on the details presently provided.
Applicant has failed to provide sufficient description based on the broad class of protein targets, binders and functions claimed.
Consequently, Claims 1-4, 6, 8, 10, 11, 14, 15, 19, 21, 24-26 and 52 are rejected on grounds of lack of written description.
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.
Claims 1-4, 6, 8, 10, 11, 14, 15, 19, 21, 24 and 52 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Chimmanamada et al. (WO 2013/158644A2, Information Disclosure Statement; July 11, 2023; Foreign Patent Documents, No. 1).
Chimmanamada discloses compounds (SDC-TRAPs) containing an HSP90 inhibitor, linker, and target protein binder (Abstract) which meets the limitation of claim 1.
Specifically, “The present invention provides pharmacological compounds including an effector moiety conjugated to a binding moiety that directs the effector moiety to a biological target of interest. Likewise, the present invention provides compositions, kits, and methods (e.g., therapeutic, diagnostic, and imaging) including the compounds. The compounds can be described as a protein interacting binding moiety-drug conjugate (SDC-TRAP) compounds, which include a protein interacting binding moiety and an effector moiety. For example, in certain embodiments directed to treating cancer, the SDC-TRAP can include an Hsp90 inhibitor conjugated to a cytotoxic agent as the effector moiety.
By example only, page 30, paragraph [00128] teaches that “In various aspects and embodiments, the present invention provides an SDC-TRAP comprising an Hsp90 binding moiety and an effector moiety, wherein the effector moiety is selectively released inside a target (e.g., cancer) cell. Selective release can be achieved, for example, by a cleavable linker (e.g., an enzymatically cleavable linker). Selective release can be used to decrease undesired toxicity and/or unwanted side effects. For example, an SDC-TRAP can be designed where an effector moiety such is inactive (or relatively inactive) in a conjugated form, but active (or more active) after it is selectively released inside a target (e.g. , cancer) cell.”
Regarding claims 2-3, Chimmanamada discloses HSP binders of formula (I) as shown below (page 8, paragraph [0045]), which meet the limitations of claim 2.
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Specifically, the Hsp90-binding moiety meets the limitations of instant claim 2’s H where W is 5- or 6-membered heteroaryl optionally substituted with 1 to 3 groups selected from R2, and V is phenyl as shown below.
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Chimmanamada’s compound of formula (I) (shown above) also meets the limitations of instant claim 4 wherein H is as shown below, where Z is CH.
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Regarding claim 6, Chimmanamada (page 8, paragraph [0046]),further teaches that: “R1 may be alkyl, aryl, halide, carboxamide or sulfonamide; R2 may be alkyl, cycloalkyl, aryl or heteroaryl,” which meets the limitations of instant claim 3 where R3 is independently (C1-C4)alkyl).
Regarding claims 8 and 10, as aforementioned, Chimmanamada teaches wherein H is:
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Regarding, claim 11, Chimmanamada (page 8, paragraph [0045]) teaches “R1 may be alkyl, aryl, halide, carboxamide or sulfonamide,” which meets the limitations of claim 11 where R1 is halo or (C1-C4)alkyl.
Regarding claims 14-15, Chimmanamada teaches where R2 is ORa, where Ra is hydrogen as shown above.
Regarding claims 19, 21 and 24, Chimmanamada teaches the following linker:
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.
In summary, by example only, SDC-TRAP-0174 (page 194, paragraph [00863]), demonstrates how Chimmanamada teaches the limitations of claims 1-4, 6, 8, 10, 11, 14, 15, 19, 21, and 24 as diagramed below.
[AltContent: rect][AltContent: rect][AltContent: textbox (R2 is OH)][AltContent: textbox (R3 is halo
Z is CH)][AltContent: textbox (R1 is C1-C4 alkyl)][AltContent: rect]
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As per MPEP 2131.02, "A generic claim cannot be allowed to an applicant if the prior art discloses a species falling within the claimed genus." The species in that case will anticipate the genus. In re Slayter, 276 F.2d 408, 411, 125 USPQ 345, 347 (CCPA 1960); In re Gosteli, 872 F.2d 1008, 10 USPQ2d 1614 (Fed. Cir. 1989).”
Chimmanamada also discloses pharmaceutical compositions containing the compounds, meeting the limitation of claim 52 as aforementioned.
Therefore, Claims 1-4, 6, 8, 10, 11, 14, 15, 19, 21, 24 and 52 are anticipated by Chimmanamada.
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, 6, 8, 10, 11, 14, 15, 19, 21, 24-26, and 51-52 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-30 of U.S. Patent No. 12,540,143 B2. Although the claims at issue are not identical, they are not patentably distinct from each other because both applications are directed towards similar compounds consisting of a BET binder, resorcinol-based compound that binds HSP90 connected by similar and/or identical linkers.
Claim 1 of ‘143 is directed towards compounds containing a BET binder (identical to target protein binder), linker and A (identical to the H moiety) of instant application and overlaps with subject matter regarding the H moiety as per instant claims 1-4, 6, 8, 10, 11, 14, 15. Instant claims 25-26 are directed towards the identical BET binder, as shown below.
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Claims 2-7 of ‘143 are directed towards A, which is identical and/or overlapping in subject matter to the H moiety of instant application as per instant claims 1-4, 6, 8, 10, 11, 14, 15, examples as shown below.
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Claims 8, 18-23 are directed towards L, linkers, which are identical and/or overlapping in subject matter to the linkers of instant application as per instant claims 19, examples as shown below.
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Claims 24-30 are directed towards compounds overlapping in subject matter to claims 1-4, 6, 8, 10, 11, 14, 15, 19, 21, 24-26 and 51-52.
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Therefore, claims 1-4, 6, 8, 10, 11, 14, 15, 19, 21, 24-26 and 51-52 are rejected on grounds of anticipation-type nonstatutory double patenting.
Claims 1-4, 6, 8, 10, 11, 14, 15, 19, 21, 24-26, and 51-52 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 5, 8, 11, 13, 15, 20-22, 25-26, 30, 32, 35, 38, and 40-42 of copending Application No. 18/031,678 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because instant claims and ‘678 are directed towards similar and/or identical compounds consisting of a BET binder, linker and resorcinol-based compound that binds HSP90.
Claim 1 of ‘678 is directed towards compounds containing a target protein binder (BET binder), a chemical moiety that binds HSP90 protein (A, which is identical to H in instant application), and linker as shown below.
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Claim 2 of ‘678 is directed to different A groups, which are similar and/or identical to the H groups recited in instant claim 2, example shown below.
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Claims 5,8,11,13 of ‘678 is directed to the BET binder which maps to instant claims 24-26, example as shown below.
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Claims 15, 20-22, and 25-26 of ‘678 map towards similar and/or identical H moieties as per instant claims 3-4, 6, 8, 10-11, and 14-15, examples as shown below.
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Claims 30, 32, 35, and 38, map towards similar and/or identical linker moieties as per instant claims 19, 21, and 24, examples as shown below.
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Claims 40-42 are directed towards identical compounds as per instant claims 51, example shown below.
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Therefore, claims 1-4, 6, 8, 10, 11, 14, 15, 19, 21, 24-26, and 51-52 are rejected on grounds of anticipation-type nonstatutory double patenting.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Relevant Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Bradner et al (WO 2016/105518 A1) discloses PROTAC compounds consisting of the identical BET binder as per claims 24-26; however, this framework utilizes a targeting ligand, degron based on thalidomide, and different classes of linkers.
Conclusion
Claims 1-4, 6, 8, 10, 11, 14, 15, 19, 21, 24-26, and 51-52 are under consideration and are rejected. No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CAROLYN L. LADD whose telephone number is (703)756-5313. The examiner can normally be reached M-Th, 7:00 am to 5:30 pm EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James H. Alstrum-Acevedo can be reached at 571-272-5548. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/C.L.L./Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622