DETAILED ACTION
STATUS OF THE APPLICATION
Receipt is acknowledged of Applicants’ Amendments and Remarks, filed 16 December 2025, in the matter of Application No. 17/419,030. Said documents have been entered on the record. The Examiner further acknowledges the following:
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 1, 30-32, 34, 39-43, 45-47, 50-52, 54-61, 65-66, and 70 are pending.
Claims 30-31 and 45 have been amended.
No claims have been cancelled.
Applicants’ election of Group II (claims 30-32, 34, 39-43, 45-47, and 54), with traverse, is acknowledged.
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 16 December 2025 has been entered.
Election/Restrictions
Applicant's election with traverse of Group II, comprising claims 30-32, 34, 39-43, 45-47, and 54, in the reply filed on 17 January 2025 is acknowledged.
Upon further consideration, in view of the compounds of Group II being found to be free of prior art, Groups I and III-VIII are rejoined as set forth below. Group IX, comprising claim 70 and drawn to a genus of small molecules without conjugation to a targeting moiety and lacking reactive groups according to Formulae (IV), (V), and (VI), respectively, remains withdrawn.
Rejoinder
Claims 30-32, 34, 39-43, 45-47, and 54 are directed to an allowable product. Pursuant to the procedures set forth in MPEP § 821.04(b), the inventions of Groups I and III-IX (claims 1, 50-52, 55-61, and 65-66) directed to a genus of conjugates as described in claim 1; a method for preparing a conjugates comprising the reaction of a compound of claim 30 with a targeting moiety; a method for imaging and a composition thereof according to a compound of claim 30; a method of detecting and a sensor composition thereof according to a compound of claim 30; a molecular switch, machine, or nanomachine according to a compound of claim 30 and a method of moving portions thereof; a method of cellular delivery comprising contacting the cell with a compound of claim 30, wherein the targeting moiety is selected to bind to a molecule associated with the cell; a method for treating proliferative diseases comprising administering a compound of claim 30, previously withdrawn from consideration as a result of a restriction requirement, are hereby rejoined and fully examined for patentability under 37 CFR § 1.104. Group IX, comprising claim 70, is not eligible for rejoinder because it appears to be directed toward a materially different genus of compounds.
Because a claimed invention previously withdrawn from consideration under 47 CFR § 1.142 has been rejoined, the restriction requirement as set forth in the Office Action mailed on 26 November 2024 is hereby withdrawn. In view of the withdrawal of the restriction requirement as to the rejoined inventions, Applicant(s) are advised that if any claim presented in a continuation or divisional application is anticipated by, or includes all the limitations of, a claim that is allowable in the present application, such claim may be subject to provisional statutory and/or nonstatutory double patenting rejections over the claims of the instant application. Once the restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable. See MPEP § 804.01.
Information Disclosure Statement (IDS)
The information disclosure statements submitted on 16 December 2025 and 24 February 2026 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the Examiner.
REJECTIONS WITHDRAWN
The status for each rejection and/or objection in the previous Office Action is set out below.
35 U.S.C.§ 103
Applicant’s arguments and amendments filed 16 December 2025, wherein on p. 16-23 of the response Applicant argues that Kim fails to explicitly teach the interchangeability of the -CO2- group with another group, because the two formulas of Kim depict a genus wherein an ester group is present or absent, but not explicitly replaced by another group. Applicant further argues that there is no reasonable motivation to combine Kim and Pardeshi, because Pardeshi does not teach that the ester group at the specific position of Kim’s compound can be replaced with an -SO2- group, and Kim is silent as to whether the ester group at the specific position can be replaced with -SO2-. In addition, Applicant argues that since Pardeshi teaches the modification of a carbonate group, wherein the ester group (-C(O)O-) within the carbonate group (-OC(O)O-) may be replaced with -SO2-, Pardeshi does not teach that the ester group (-C(O)O-) in Kim’s compounds comprising a carbamate (-OC(O)N-) structure can be readily replaced with -SO2-. Therefore, Applicant argues that one of ordinary skill in the art would not have been motivated to combine Kim and Pardeshi to arrive at the amended claims with a reasonable expectation of success. Finally, Applicant argues that since amended claims 30-31 incorporate the limitation wherein L’ is connected to -SO2-via O only, even if the ester -CO2- of Kim’s compound were replaced with -SO2-, the claimed conjugate could not be derived from Kim and Pardeshi.
These arguments have been fully considered and are persuasive to overcome the rejections of claims 30-32, 34, 40, 43, 46, and 54 under 35 U.S.C. 103 as being unpatentable over Kim et al. (WO 2017/089895 A1; PTO-892 of 04-18-2025; hereinafter “Kim”), in view of Pardeshi et al. (Org. Lett. 2018, 20, 4-7; PTO-892 of 04-18-2025; hereinafter “Pardeshi”) on record of the Office Action dated 16 September 2025. Neither Kim nor Kim in view of Pardeshi would sufficiently motivate one of ordinary skill to arrive at compounds corresponding to the genus of amended claims 30-31. Therefore, the rejections are withdrawn.
NEW Claim Rejections - 35 USC § 112
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 30, 32, 34, 49-43, 45-47, 50-52, 54-61, and 65-66 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.
Claim 30 recites “…Z’, independently for each occurrence, is absent…” in line 6. Yet, claim 30 also recites “…provided that at least one occurrence of Z’ connects the structure of Formula (Ia) to the targeting moiety…” in lines 8-10. Thus, it is unclear as written whether or not Z’ can or cannot be absent in the described genus. Further clarification is required. The Examiner notes that adequately addressing this ambiguity would ameliorate this claim rejection.
Regarding claims 32, 34, 49-43, 45-47, 50-52, 54-61, and 65-66, these dependent claims do not resolve the indefiniteness of claim 30 detailed above.
Claim Rejections - 35 USC § 112(a) – Scope of Enablement
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 65-66 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for treating the recited proliferative diseases, does not reasonably provide enablement for preventing the recited proliferative diseases. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
Enablement is considered in view of the Wands factors (MPEP § 2164.01(a)). The court in Wands states: "Enablement is not precluded by the necessity for some experimentation such as routine screening. However, experimentation needed to practice the invention must not be undue experimentation. The key word is ‘undue,’ not 'experimentation.'" (Wands, 8 USPQ2d 1404). Clearly, enablement of a claimed invention cannot be predicated on the basis of quantity of experimentation required to make or use the invention. "Whether undue experimentation is needed is not a single, simple factual determination, but rather is a conclusion reached by weighing many factual considerations." (Wands, 8 USPQ2d 1404). The factors to be considered in determining whether undue experimentation is required include: (1) the quantity of experimentation necessary, (2) the amount or direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims. While all of these factors are considered, a sufficient amount for a prima facie case are discussed below.
The nature of the invention
Claim 65 encompasses a method for treating proliferative disease comprising administering a compound of claim 30. The term “treating” as recited in instant claim 65 will be interpreted in a manner consistent with the written description as including prophylactic (i.e., it protects the host against developing the unwanted condition) and/or therapeutic treatment (Specification; page 8, lines 17-21). The term “proliferative disease” as recited in instant claim 65 will be interpreted in a manner consistent with the written description as encompassing abnormal cell growth of tumor cells and benign and malignant cells of other proliferative diseases in which aberrant tyrosine kinase or serine/threonine kinase activation occurs (Specification; page 9, lines 6-15). Claim 66 encompasses the method of claim 65, wherein the proliferative disease is selected from autoimmune disorders, chronic inflammatory conditions, hyperproliferative disorders, viral infections, osteoarthritis, and atherosclerosis. The term “hyperproliferative disorders” as recited in instant claim 66 will be interpreted in a manner consistent with the written description as encompassing, for example, breast cancer and lung cancer (Specification; page 148, line 21). Thus, claim 65 and dependent claim 66 encompass a method for preventing cancer.
The breadth of the claims
The claims are broad in that they encompass the prevention of the recited cancers, as well as a broad range of additional therapeutic agents.
Thus, in its broadest reasonable interpretation, preventing the recited cancers indicates that that the onset of the cancer never occurs and the patient’s health is protected and preserved.
The amount or direction provided by the inventor / the existence of working examples
The examples disclose synthetic scheme for conjugates comprising compounds having structures of Formula (Ia) of claim 30 on which instant claims 65-66 depend, in addition to cell cytotoxicity assays of the protein-drug conjugates (Specification; Examples 46-48 and 51-52; Table 3).
The examples do not demonstrate prevention of the cancers recited in the instant claims. The disclosure also does not identify, or demonstrate through working examples, a method that can be used by one of ordinary skill in the art to predictably determine that a subject would develop one of the claimed cancers in order to establish that cancer was prevented using the claimed method.
The state of the prior art / the level of predictability in the art
There are no art recognized methods that can be used to predictably determine that cancer onset was prevented using the claimed method or to identify patients who would predictably develop cancer in order to identify that prevention was achieved using therapeutic approaches. Rather, the state of the art indicates that cancer development was not predictable.
Lewandowska, A.M., et al (2017) Environmental risk factors for cancer – review paper Ann. Agric. Environ. Med. 26(1); 1-7 teaches that the cancerous process is a result of disturbed cell function. This is due to the accumulation of many genetic and epigenetic changes within the cell, expressed in the accumulation of chromosomal or molecular aberrations, which leads to genetic instability. It is difficult to assess the validity of individual etiological factors, but it can be concluded that interaction of various risk factors has the largest contribution for the development of cancer. Environmental, exogenous and endogenous factors, as well as individual factors, including genetic predisposition, contribute to the development of cancer (page 1, right column, paragraph 1). Lewandowska discusses numerous factors that contribute to the development of cancer including physical factors such as exposure to electromagnetic fields, ionizing radiation, and ultraviolet radiation (pages 2-3); chemical factors including tobacco smoking, alcohol, and other chemicals (pages 3-4); and biological factors including diet, physical activity, mutagenic and carcinogenic compounds in food, nitrosoamines, and infections (pages 4-5). Lewandowska teaches that, additionally, some epidemiological research suggests that the influence of environmental factors will further affect the cell’s genetic material. This is connected with the spreading of carcinogens in various geographical zones. While some are well known and can be modified, there are certain factors that cannot be fully controlled, such as industrialization (page 6, left column, paragraph 2).
The teachings of Lewandowska demonstrate that, while it was known that cancer is caused by disturbed cell function, numerous factors have been identified that could lead to such disfunction and cell disfunction is likely caused by the interaction of various risk factors. Lewandowska also teaches factors such as genetic predisposition and environmental factors that can contribute to the formation of cancer but are beyond the control of an individual subject. These teachings demonstrate that there was no specific known cause of cancer and, therefore, suggest that there would be no method to predictably determine that cancer would have developed in order to establish that it was prevented.
Cuzick, J. (2017) Preventive therapy for cancer Lancet Oncol 18; e472- e482 teaches the use of therapeutic preventative measures in addition to weight control and physical activity, such as low-dose aspirin for adults without the risk of hypertension or gastrointestinal bleeding, universal HPV vaccination, and other therapies such as anti-oestrogen drugs for breast cancer prevention targeting high-risks groups to “maintain a favorable benefit-risk ratio” (abstract). While Cuzick is identifying therapeutic regimens to prevent cancer, Cuzick also teaches “the balance of risks and benefits is inherently more challenging for preventative than for therapeutic interventions. Only a small fraction of the apparently healthy people who receive a preventative treatment would ultimately develop the specific type of cancer being targeted. Moreover, the absence of the cancer is not quantifiable at an individual level, whereas all those treated will incur a risk of side-effects which are identifiable on an individual basis” (page e472, left column, paragraph 2).
Cuzick demonstrates that the prevention of cancer is not predictable and that numerous factors contribute to the development of cancer. Additionally, Cuzick teaches difficulties in preventing cancer with therapeutic methods and specifically states that the absence of cancer is not quantifiable on an individual level, a statement which demonstrates that the determination of whether or not cancer was prevented is unpredictable.
DeCensi, A., et al (2015) Barriers to preventative therapy for breast and other major cancers and strategies to improve uptake eCancer 9(595); 1-12 teaches that the global cancer burden continues to rise but the utilization of preventative therapy has been poor due to various barriers. DeCensi teaches barriers such as the lack of physician and patient awareness, fear of side effects, and licensing and indemnity issues. DeCensi provides a review discussing the barriers and proposes strategies to overcome them including improving awareness and countering prejudices by highlighting the important differences between preventative therapy and cancer treatment. DeCensi further teaches that future research to improve therapeutic cancer prevention needs to include improvements in the prediction of benefits and harms and improvements in safety profiles of existing agents by experimentation with dose (abstract). DeCensi teaches that for preventative therapy, we cannot identify individuals whose cancer was prevented or risk was substantially reduced because of the lack of measurable biomarkers of efficacy that currently exist for other diseases such as cardiovascular diseases, prevention of diabetes complications or osteoporotic bone fractures. Therefore, from that person’s point of view, they either took medication unnecessarily or, in the worst-case scenario, unnecessarily suffered the adverse effects of such therapy (page 2, paragraph 1).
The teachings of DeCensi demonstrate that, while preventative therapies could be beneficial if various barriers are overcome, there was no method known that could be used to identify individuals whose cancer was prevented because of the lack of measurable biomarkers.
The teachings of Lewandowska, Cuzick, and DeCensi demonstrate that there was no art recognized method of determining whether a patient would predictably develop cancer and, therefore, there is no predictable way to determine that cancer was prevented using the claimed method.
The quantity of experimentation needed to make or use the invention based on the content of the disclosure
As discussed above, there is no disclosed or art recognized method through which an ordinarily skilled artisan would be able to determine that a subject would have predictably developed one of the claimed cancers in order to apply the claimed treatment as a preventative measure. Furthermore, there is no known or disclosed method that could be used to establish that cancer was prevented as there is no predictable way to know that the subject being treated would have developed a cancer without the treatment. As such, in order to implement the invention as claimed, one of ordinary skill in the art would have to participate in undue experimentation to identify a method that could be used to establish that cancer was prevented, with the possibility that no such method could be found.
In view of the Wands factors discussed above, a person of ordinary skill in the art would have to engage in undue experimentation to practice the full scope of the claimed invention. As such, the instant claims were determined to not meet the scope of enablement requirement of 35 USC 112(a).
NEW Double Patenting Rejections
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, 30-31, 41, 43, 45-46, 54-55 and 57 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 8-9, 11, 15-16, and 18-20 of U.S. Patent No. 11,753,431 B2.
Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding instant claims 1, 30-31, and 41, claim 1 of U.S. Patent No. 11,753,431 B2 teaches the following:
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This claimed genus anticipates the genus represented by Formula (I’) and Formula (I’’) of instant claim 1 when Ar is a 6-membered aryl or 6-membered heteroaryl ring and when x is 0 or when y is 0.
Further regarding instant claims 30 and 41, the genus representing a structure of Formula (I’’) of claim 1 of U.S. Patent No. 11,753,431 B2, anticipates the genus represented by Formula (Ia) of instant claim 30 when L’ is attached to the SO2 via O, Ar is a 6-membered aryl or 6-membered heteroaryl ring and when x is 0 or when y is 0, and of instant claim 41 when L’ is attached to the SO2 via O, Ar is a 6-membered aryl or 6-membered heteroaryl ring, and when x is 0.
Further regarding instant claim 31, the genus representing a structure of Formula (I’’) of claim 1 of U.S. Patent No. 11,753,431 B2, in addition to the limitation wherein Z’ further comprises a reactive group as recited in claims 8-9 of U.S. Patent No. 11,753,431 B2, anticipates the genus represented by Formula (Ia) of instant claim 31 when L’ is attached to the SO2 via O, Ar is a 6-membered aryl or 6-membered heteroaryl ring and when x is 0 or when y is 0.
Regarding instant claim 43, claim 11 of U.S. Patent No. 11,753,431 B2 teaches every limitation of the instant claim.
Regarding instant claim 45, the genus of claim 15 of U.S. Patent No. 11,753,431 B2 anticipates every limitation of the claimed genus of instant claim 45.
Regarding instant claim 46, claim 16 of U.S. Patent No. 11,753,431 B2 teaches every species as recited in the claim.
Regarding instant claim 54, claim 18 of U.S. Patent No. 11,753,431 B2 teaches a composition comprising the claimed conjugate and a pharmaceutically acceptable carrier or excipient.
Regarding instant claim 55, claim 19 of U.S. Patent No. 11,753,431 B2 teaches an imaging composition comprising the claimed conjugate.
Regarding instant claim 57, claim 20 of U.S. Patent No. 11,753,431 B2 teaches a sensor compound comprising the claimed conjugate.
Claims 30-31, 40-41, 43, and 45-46 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 7-8, and 11-12 of U.S. Patent No. 12,479,927 B2.
Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding instant claims 30-31 and 41, claim 1 of U.S. Patent No. 12,479,927 B2 teaches the following:
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Further regarding instant claims 30 and 41, the genus representing a compound of Formula (Ia) of claim 1 of U.S. Patent No. 12,479,927 B2 anticipates the genus represented by Formula (Ia) of instant claim 30 when L’ is attached to the SO2 via O, Ar is a 6-membered aryl or 6-membered heteroaryl ring, and when x is 0 or when y is 0, and of instant claim 41 when L’ is attached to the SO2 via O, Ar is a 6-membered aryl or 6-membered heteroaryl ring and when x is 0, and of instant claim 41 when L’ is attached to the SO2 via O, Ar is a 6-membered aryl or 6-membered heteroaryl ring, and when x is 0. The latter limitation (x is 0) is further disclosed in claim 8 of U.S. Patent No. 12,479,927 B2.
Further regarding instant claims 31, the genus representing a compound of Formula (Ia) of claim 1 of U.S. Patent No. 12,479,927 B2, in addition to the limitation incorporating reactive groups into Z’as recited in claim 14 of U.S. Patent No. 12,479,927 B2, anticipates the genus represented by Formula (Ia) of instant claim 31 and teaches every limitation of instant claim 40 when L’ is attached to the SO2 via O, Ar is a 6-membered aryl or 6-membered heteroaryl ring and when x is 0 or when y is 0.
Regarding instant claim 43, claim 7 of U.S. Patent No. 12,479,927 B2 teaches every limitation of the instant claim.
Regarding instant claim 45, the genus of claim 11 of U.S. Patent No. 12,479,927 B2 anticipates every limitation of the claimed genus of instant claim 45.
Regarding instant claim 46, claim 12 of U.S. Patent No. 12,479,927 B2 teaches every species as recited in the claim.
Allowable Subject Matter
Claims 1, 30-32, 34, 39-43, 45-47, 50-52, 54-61, and 65-66 would be allowable if rewritten or amended to overcome the rejections of claims 30, 32, 34, 49-43, 45-47, 50-52, 54-61, and 65-66 under 35 U.S.C. 112(b), the rejections of claims 65-66 under 35 U.S.C. 112(a), and the double patenting rejections of claims 1, 30-31, 40-41, 43, 45-46, 54-55, and 57 set forth in this Office Action. The Examiner further notes that filing a terminal disclaimer would ameliorate the double patenting rejections.
The following is a statement of reasons for the indication of allowable subject matter:
The closest prior art to the claimed invention is Kim (of record). The claims are distinguished from the prior art for the reasons set forth above.
Kim teaches antibody-drug conjugates comprising branched linkers and methods related thereto, wherein a plurality of active agents are conjugated to an antibody through at least one branched linker (Kim; Title; Abstract). Kim further teaches a species comprising alpha-amanitin as the active agent (i.e., as in (Q)q of Formula (Ia) when q = 1) attached through its phenoxy O atom to a linker that further attaches to a CO2 group via a heteroatom (i.e., as in (L’)w of Formula (Ia) when q = 1 and the heteroatom is N, to form a carbamate functional group) and is further connected to -CH2- group (i.e., as in X of Formula (Ia) when X = -C(Ra)(Rb)- and Ra = Rb = H) followed by a 6-membered aryl ring (i.e., as in Ar of Formula (Ia)); the aryl ring has an ortho-substituted amide moiety with a pegylated linker comprising a terminal hydroxylamine O-ether reactive group that serves as a precursor for antibody conjugation (i.e., as in Z’ of Formula (Ia)); finally, the aryl ring further possesses a para-substituted, enzyme-cleavable glucuronide triggering group (i.e., as in (Y’)x-TG of Formula (Ia) when x = 1) that, when cleaved, generates an O atom capable of initiating release of CO2 and the drug-linker conjugate (i.e., as in (Q)q-(L’)w of Formula Ia).
Kim fails to teach an -SO2- group connecting the active agent to the Ar ring, as recited in instant claims 1 and 30-31, and the genus and species of Kim do not explicitly suggest interchangeability of the carbamate moiety of Kim to arrive at conjugates and compounds comprising an -SO2- group connecting the active agent.
The prior art of record does not teach or suggest the compounds and conjugates comprising a cleavable linker and a -SO2- functional group positioned proximal to a nucleophilic heteroatom to release the triggering groups as recited in instant claims 1 or 30-31, and this deficiency is not sufficiently addressed by Kim alone or in combination with supporting prior art such as Pardeshi (on record of the previous Office Action dated 16 September 2025), for the reasons set forth above. An expanded search of the prior art over the scope of the genus of compounds described in instant claims 1 and 30-31 failed to identify prior art that teaches compounds and conjugates that meet the structural limitations of the instant claims. Therefore, the prior art of record provides no teachings or direction regarding the instantly claimed conjugates and compounds and consequently does not sufficiently motivate one of ordinary skill in the art to arrive at the claimed invention with a reasonable expectation of success. Nor did an expanded search provide any further pertinent references.
Conclusion
The prior art made of record and not relied upon is considered pertinent to Applicant’s
disclosure.
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/D.R./
Examiner, Art Unit 1692
/AMY C BONAPARTE/Primary Examiner, Art Unit 1692
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