DETAILED ACTION
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, filed 2 February, 2023, is a national stage application of PCT/KR2021/010298, filed 4 August, 2021, which claims foreign benefit of Application KR10-2021-0102226, filed 3 August, 2021; KR10-2020-0097553, 4 August, 2020; and KR10-2020-0097550, 4 August, 2020.
Status of the Application
Receipt is acknowledged of Applicant’s claimed invention, filed 30 June, 2026, in the matter of Application N° 18/040,323. Said documents have been entered on the record.
Claim 1 is amended. Claim 5 is canceled. No new matter was introduced.
Claims 10-16 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Group II – Method Claims, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 1 October, 2025.
Thus, Claims 1, 6, and 8 represent all claims currently under consideration.
Response to Amendment/Arguments
Claim 5 is canceled. Therefore, the rejection of this claims under 35 U.S.C. 103 is moot.
Applicant’s arguments regarding Vincent have been fully considered but are not persuasive. Applicant argues, inter alia, that Vincent does not recognize the functional significance of the NH2 group of the TLR7/8 agonist as an active site and treats amino and hydroxyl groups as interchangeable attachment sites (Remarks, Pg 8-12). However, Vincent expressly discloses TLR7/8 agonists, including imiquimod and resiquimod, having the linker attached through the same amino group recited in the instant claims. The fact that Vincent does not characterize this amino group using Applicant’s terminology as an “active site,” or does not attribute attenuation of agonist activity to the same mechanism advanced by Applicant, does not distinguish the expressly disclosed attachment at the claimed NH2 position. See MPEP §2112. Further, Vincent’s disclosure of alternative attachment sites does not constitute a teaching away from attachment through the amino group (Remarks, Pg 16). As explained in MPEP §2143.01(I), "the prior art’s mere disclosure of more than one alternative does not constitute a teaching away from any of these alternatives because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed." Vincent expressly presents amino-group conjugation as an available embodiment and does not criticize, discredit, or otherwise discourage its use.
Applicant further argues that Vincent’s binder merely functions as a passive targeting vehicle and that Vincent therefore provides no basis for the claimed sequential activity in which the anticancer agent acts first and the TLR7/8 agonist subsequently acts following linker cleavage (Remarks, Pg 12-14). This argument is not persuasive because it is based principally upon Vincent’s exemplified Affirmer/VbP conjugates and does not account for the broader disclosure of Vincent. As discussed in greater detail in the rejection below, Vincent expressly contemplates biologically functional binder moieties, including antagonists of checkpoint proteins, together with cleavable drug conjugates in which pharmacological activity of the conjugated drug is attenuated and the free drug is subsequently released by linker cleavage. Thus, Vincent is not limited to a system in which the binder serves only as a passive carrier. Further, Applicant’s argument that Vincent could not reasonably predict the particular therapeutic effects subsequently identified by Applicant does not establish a lack of reasonable expectation of success (Remarks, Pg 11-12). As explained in MPEP §2143.02, the reasonable-expectation-of-success inquiry concerns the likelihood of success in combining or modifying the prior art disclosures to meet the limitations of the claimed invention. The relevant teachings of Vincent and their relationship to the limitations of amended claim 1 are addressed in the rejection below.
Applicant’s evidence and arguments concerning unexpected results, including asserted enhanced antitumor efficacy, suppression of the initial immune response, and restoration of TLR7/8 agonist activity following cleavage, have also been considered (Remarks, Pg 14-16). Objective evidence of nonobviousness must have a nexus to the claimed invention and must be commensurate in scope with the claims for which the evidence is offered. See MPEP §§716.01(b) and 716.02(d). As discussed below, the evidence relied upon by Applicant is directed to particular tested conjugates and must be considered in view of the substantially broader scope of amended Claim 1, including the recited genera of TLR7/8 agonists, anticancer agents, linker types, and linker bonds. Applicant’s evidence has been considered together with the evidence supporting the prima facie case of obviousness but does not overcome the rejection for the reasons discussed below.
Accordingly, Applicant’s arguments have been considered but are not persuasive of patentability. The rejection under U.S.C. 103 has been reformulated below to address amended Claim 1 and Applicant’s arguments.
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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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, 6, and 8 are rejected under 35 U.S.C. 103 as being unpatentable over Vincent et al. (WO 2019/236567 A2), hereinafter Vincent.
Regarding Claims 1 and 8, Vincent teaches a tumor microenvironment-activated drug-binder conjugate comprising: (i) a cell binding moiety which is an antibody (‘567, Pg. 3, Line 28), (ii) a drug moiety which is TLR7/8 (‘567, Pg. 9, Line 17), and (iii) a linker moiety which is cleaved completely so as to release the drug moiety (‘567, Pg. 4, Lines 14), wherein L2 is p-aminobenzyloxycarbonyl (PABC), a self immolative linker, thereby providing the recited carbamate bond (‘567, Pg. 8, Lines 7-8). Furthermore, Vincent exemplifies the connection for TLR7/8 agonists at the active site (NH2) as shown below (‘567, Pg. 105.)
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Regarding Claim 6, Vincent teaches the linker L1 is a polyether such as a poly(ethylene glycol) (‘567, Pg. 8, Line 16).
Applicant asserts that the invention lies in conjugating a functional therapeutic agent to a TLR7/8 agonist through the active NH2 site of the agonist by means of a cleavable linker, such that the anticancer agent acts first while the TLR7/8 agonist is initially inactivated, followed by cleavage of the linker and recovery of the TLR7/8 agonist activity. However, the teachings of Vincent, considered as a whole, would have rendered the presently claimed complex prima facie obvious to one of ordinary skill in the art.
Vincent expressly teaches TLR7/8 agonists, including imiquimod and resiquimod, as drug moieties in its cleavable conjugates and depicts attachment of such agonists through the same NH2 position recited in the instant claim. Vincent further teaches that the pharmacological activity of the drug moiety is attenuated while present in the conjugate and that cleavage of the linker releases the drug moiety (‘567, Pg. 2, Summary). Thus, Vincent teaches the same general functional relationship required by the instant claim: a TLR7/8 agonist attached through the recited NH2 position in a cleavable conjugate, with activity of the conjugated drug attenuated prior to cleavage and the drug subsequently made available upon cleavage. The fact that Vincent does not identify the NH2 group using Applicant’s terminology as the “active site,” or attribute attenuation to the particular active-site masking mechanism proposed by Applicant, does not alter Vincent’s express teaching of attachment at that position. See MPEP §2112.
Furthermore, Vincent’s cell-binding moiety is not limited to a biologically passive targeting vehicle. Vincent teaches anti-PD-L1 Affirmer cell-binding moieties and experimentally demonstrates their biological activity. In particular, Vincent demonstrates binding of the anti-PD-L1 Affirmer Fc fusion proteins to PD-L1 (‘567, Pg 203, Example 4), modulation of T-cell responses by an anti-PD-L1 Affirmer Fc (‘567, Pg 204, Example 6), and, in a Pd-1/PD-L1 cell-based blockade assay, demonstrates that the anti-PD-L1 Affirmer blocks the PD-1/PD-L1 interaction, releases the inhibitory signal, and results in T-cell activation (‘567, Pg 204, Example 7). Thus, contrary to Applicant’s characterization of Vincent’s binder as merely a delivery vehicle, Vincent teaches a cell-binding moiety having independent biological activity consistent with the broadly recited anticancer agents of instant Claim 1.
In view of Vincent’s teaching of a biologically active anti-PD-L1 cell-binding moiety together with its teaching of cleavable conjugates in which pharmacological activity of the conjugated drug is attenuated prior to cleavage and the drug is subsequently released, one of ordinary skill in the art would have had a reason to employ Vincent’s anti-PD-L1 cell-binding moiety with Vincent’s expressly disclosed TLR7/8 agonist payload attached through the depicted NH2 position and cleavable linker. Such an arrangement would permit the anti-PD-L1 moiety to exert its checkpoint-blocking activity while the TLR7/8 agonist remains conjugated and attenuated, followed by activity of the TLR7/8 agonist upon cleavage and release, thereby providing the recited sequence in which the anticancer agents acts first and the TLR7/8 agonist subsequently acts following linker cleavage.
One of ordinary skill in the art would have had a reasonable expectation of success because Vincent independently demonstrates the biological activity of the anti-PD-L1 cell-binding moiety, expressly teaches attenuation of drug activity in the conjugated state and subsequent release of the drug by cleavage, and expressly identifies TLR7/8 agonists and the claimed NH2 attachment as suitable for the disclosed conjugate architecture. See MPEP §2143.02.
Vincent’s additional disclosure that TLR agonist may be coupled through other functional groups, including free hydroxyl groups, does not negate its express disclosure of coupling through the NH2 group. The prior art’s disclosure of more than one alternative does not constitute a teaching away from any of the disclosed alternatives absent criticism, discrediting, or discouragement of the claimed alternatives. See MPEP §2143.01(I).
Communication
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Donna M. Nestor whose telephone number is (703)756-5316. The examiner can normally be reached generally (w/flex): 5:30a-5p EST M-Th.
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/D.M.N./ Examiner, Art Unit 1627
/SARAH PIHONAK/Primary Examiner, Art Unit 1627
