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 1 September, 2023, is a national stage application of PCT/JP2022/009003, filed 2 March, 2022, which claims foreign benefit of applications JP2021-146833, filed 9 September, 2021 and JP2021-034026, filed 4 March, 2021.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 16 June, 2026, is acknowledged and has been considered.
Status of the Application
Receipt is acknowledged of Applicant's claimed invention, filed 17 July, 2026, in the matter of Application N° 18/548,716. Said documents have been entered on the record.
Claims 2, 5-7, 10, and 12-14 are amended. Claims 1, 3-4, and 6 are canceled. Claim 15 is new. No new matter was introduced.
Claims 8-9 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 5 March, 2026.
Thus, Claims 2, 5, 7 and 10-15 represent all claims currently under consideration.
Response to Amendment/Arguments
Claims 1, 3-4, and 6 have been canceled. Therefore, the rejections of these claims under 35 U.S.C. 112(a), 112(b), 102(a)(1), and non-statutory double patenting are moot.
Applicant’s amendments are sufficient to overcome the previous rejections under 35 U.S.C. 112(a) and 112 (b).
Applicant's arguments filed 17 July, 2026 regarding the rejection under 35 U.S.C. 102(a)(1), have been fully considered and are persuasive in view of the amendments to the claims. In particular, amended independent claim 2 now requires Lb to comprise a structure derived from an amino acid having a structure containing an alicyclic group of 5 to 10 carbon atoms. Kung’s compound 7, previously relied upon as anticipating the claimed compound, instead comprises an aromatic phenyl-containing structure in the corresponding linker region. Accordingly, Kung’s compound 7 does not expressly disclose the newly recited alicyclic limitation, and the rejection of Claims 1-7 and 10-14 under 35 U.S.C. 102(a)(1) over Kung is withdrawn.
Applicant further argues that the disclosed PSMA-NAT-DA1 compound demonstrates advantageous or superior properties attributable to the newly recited Lb (Remarks, Pg 14-15). This argument has been considered but is not persuasive as evidence of patentability of the presently claimed subject matter. The comparison relied upon by Applicant is between PSMA-NAT-DA1 and PSMA-DB, compounds that differ in multiple structural respects and not merely in the structure of Lb. In particular, PSMA-DB does not contain an albumin-binding moiety in the structure. Thus, the cited comparison does not isolate the alicyclic structure of Lb as the feature responsible for the asserted superiority, and does not establish a nexus between the asserted result and the particular feature distinguishing the amended claims from the prior art.
Moreover, the asserted results are based upon a particular exemplified compound, whereas claim 2 encompasses a substantially broader genus, including embodiments wherein m is 0 and Lb is therefore absent. Accordingly, the evidence relied upon by Applicant is not commensurate in scope with the claims. While the amendment is sufficient to distinguish the presently claimed subject matter from Kung for purposes of anticipation, it does not establish that the newly recited structural modification would have been nonobvious to one of ordinary skill in the art. The claims are therefore considered below under 35 U.S.C. 103.
Applicant’s argument regarding the provisional nonstatutory double patenting rejection has been fully considered but is not persuasive (Remarks, Pg 16).
Applicant argues that the presently claimed compounds are patentably distinct from the compounds claimed in copending Application No° 17/904,792 because amended independent claim 2 requires linker Lb to comprise a structure derived from an amino acid having a structure containing an alicyclic group of 5 to 10 carbon atoms, whereas Applicant asserts that the compounds of the reference application do not contain such an alicyclic amino-acid derived linker.
Examiner agrees that the presently claimed Lb limitation is not expressly depicted in Formula 2 of ‘792. However, the relevant inquiry for nonstatutory double patenting is not whether the claims are identical, but whether the presently claimed subject matter constitutes a patentably distinct variation of the subject matter claimed in the copending application.
The currently pending claims of the ‘792 application, filed 9 February, 2026, recite compounds having the same general functional architecture as presently claimed, including a chelating moiety, a target-molecule-binding moiety, and an albumin-binding moiety, with the respective functional moieties connected through a linker structure. In the PSMA embodiment, ‘792 claim 1 further requires a linker between the chelating moiety and albumin-binding moiety that is not derived from ethylene glycol and includes an alkyl group having 1 to 8 carbon atoms and a carboxy group. The ‘792 claims further expressly require the albumin-binding moiety to have Formula B1 (identical to instant Formula B1), and dependent claim 17 encompasses the PSMA-binding structure of C3 (identical to instant C1.) Thus, the distinction relied upon by Applicant resides principally in the structural selection of the intervening linker, namely the presently claimed incorporation of an amino-acid-derived linker containing a 5- to 10-membered alicyclic group.
As discussed in the new provisional nonstatutory double patenting rejection below, Buckton et al. establishes that incorporation of cyclic amino-acid residues into peptide-containing structures was a known structural modification for imposing conformational restriction. Buckton et al. specifically describes incorporation of cycloalanines into peptide structures as a strategy for controlling molecular conformation and further describes cyclopropane-containing tethers as useful conformationally restricting structural elements.
Accordingly, the mere absence from the ‘792 claims of an express recitation of the presently claimed alicyclic amino-acid-derived Lb does not establish patentable distinctness. Rather, the presently claimed Lb represents an obvious structural modification of the linker present in the otherwise closely related compounds claimed in the ‘792 application, for the reasons set forth below.
Applicant’s argument therefore does not overcome the double patenting rejection. The rejection is updated below in view of the instant amendments, presently pending claims of the ‘792 application, and the additional teachings of Buckton et al.
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 2, 5, 7 and 10-15 are rejected under 35 U.S.C. 103 as being unpatentable over Kung (WO 2020/220023 A1, of previous record), and further in view of Subbaiah and Meanwell (J. Med. Chem. 2021, 64, 14046−14128).
Regarding Claims 2, 5, 7 and 15, Kung teaches Compound 7 (‘023, Pg 23, Structure 2, Pg 41, Scheme 10, and Pg 65, Table 1), shown below top, which significantly overlaps the genus of Formula 1 of Claim 2, wherein the chelating part A1 is DOTA (as in instant Claims 2 and 5), the albumin-binding part B is B1 (as in instant Claims 2 and 7), the PSMA molecule-binding part C is C1 (as in instant Claim 2), wherein m and n are each independently 1, and wherein A1 is bonded to La and at a different position Lb, by different linker structures (as in instant Claim 2); and the species Compound 205 (as in instant Claim 15), shown below bottom.
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‘023 Compound 7
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Instant PSMA-NAT-DA1
Kung’s Compound 7 discloses Lb comprising a phenyl ring, rather than a structure containing an alicyclic of 5- to 10- carbon atoms.
However, Subbaiah and Meanwell teach that replacing a phenyl ring with saturated carbocyclic bioisosteres was an established medicinal-chemistry strategy precisely because such replacements were known to alter useful physicochemical properties. Specifically, Subbaiah and Meanwell teach the saturation of a phenyl ring to afford a cyclohexane results in increased lipophilicity that is moderated by reducing the ring size. Additionally, the data compiled in Table 5 indicate that the effects of these structural edits on aqueous solubility, membrane permeability, HSA binding, CYP3A4 inhibition and clearance in HLM are relatively modest (Pg 14050-14052, Table 5.)
Regarding Claims 10-11, Kung teaches a complex comprising the compound and a radioactive metal ion coordinated to the chelating moiety. Such a complex corresponds to the claimed “radiolabeled compound,” as coordination of a radioactive metal ion to the chelating portion of the compound results in a radiolabeled form of the compound. Kung teaches that the compound forms stable chelating complexes with various radioactive metals, including but not limited to 68Ga (for diagnostic) as well as 177Lu (for radionuclide therapy) (‘023, Abstract, Pg. 4-5, Schemes 4-5, and Pg. 10, Para 0022).
Regarding Claim 12, Kung teaches pharmaceutical compositions comprising a pharmaceutical acceptable carrier and a compound or complex as above (‘023, Pg. 33, Para 0076).
Regarding Claim 13, Kung teaches radiolabeled complexes formed by coordination of a radioactive metal ion to the chelating moiety of the disclosed compounds (‘023, Pg. 4-5 and 9-10, Schemes 4-6). The formation of such complexes inherently requires coordinating the compound to a radioactive metal ion as recited in the claim.
Regarding Claim 14, as set forth above with respect to Claims 2, 5, 7 and 15, Kung teaches Compound 7, which significantly overlaps the claimed compounds, including those corresponding to the structure of Formula 1S. Because Kung discloses Compound 7 having the same structural framework as formula 1S, and further discloses complexes of such compounds with radioactive metal ions coordinated to the chelating moiety (‘023, Pg. 4-5 and 9-10, Schemes 4-6), Kung necessarily teaches coordinating such compounds with radioactive metal ions.
Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time of the invention to modify the phenyl-containing linker structure of Kung’s Compound 7 by replacing the phenyl ring with an alicyclic carbocyclic ring as taught by Subbaiah and Meanwell. Kung expressly teaches modification of linker structures as a means of modifying the properties of PSMA-targeting radioligand conjugates, while Subbaiah and Meanwell teach that replacement of a phenyl ring with saturated carbocyclic rings, including cycloalkyl rings, constitutes a known bioisosteric modification useful in medicinal-chemistry lead optimization. In particular, Table 5 of Subbaiah and Meanwell demonstrates phenyl-to-cycloalkyl bioisosteric substitutions and the resulting modulation of physicochemical properties. One of ordinary skill in the art therefore would have been motivated to employ the known phenyl-to-cycloalkyl bioisosteric substitution taught by Subbaiah and Meanwell in the corresponding linker region of Kung’s Compound 7 in order to obtain an analogous PSMA-targeting conjugate while predictably modifying or optimizing its physicochemical and pharmacokinetic properties.
One of ordinary skill in the art would have had a reasonable expectation of success because Subbaiah and Meanwell expressly identify saturated carbocyclic rings as useful phenyl bioisosteres and provide matched molecular-pair data demonstrating successful substitution with increased lipophilicity, while Kung teaches that its linker structures may be modified while retaining the functional PSMA-targeting conjugate architecture. Thus, the proposed modification merely applies a known bioisosteric substitution to a known modifiable linker element using established medicinal-chemistry techniques, with a reasonable expectation of obtaining a viable conjugate retaining the desired PSMA- targeting functionality.
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 2, 5, 7 and 10-15 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over Claim 1, 8-12 and 14-17 of copending Application No° 17/904,792 in view of Buckton et al. (Chem. Eur. J. 2021, 27, 1487 – 1513), hereinafter Buckton.
Although the claims at issue are not identical, they are not patentably distinct from each other. The presently pending claims of the ‘792 application, filed 9 February, 2026, encompass compounds having the same general functional architecture as presently claimed, including a chelating moiety capable of coordination to a radioactive metal ion, a target-molecule-binding moiety, an albumin-binding moiety, and linker structure joining the respective functional portions. Claim 1 of ‘792 further requires, for PSMA-binding compounds, a linker structure between the chelating moiety and the albumin-binding moiety bind that is not derived from ethylene glycol and which includes an alkyl group having 1 to 8 carbon atoms and a carboxy group and requires the albumin-binding moiety to possess Formula B1. Claim 17 further encompasses the PSMA-binding moiety represented by Formula C3, while Claims 8-12 and 19 encompass labeling precursors and radioactive-metal-labeled compounds and Claim 18 recites a linker structure derived from a compound capable of forming an amide bond equivalent to the instant limitation for La.
The instant claims differ insofar as linker Lb is further defined as comprising a structure derived from an amino acid having a structure containing an alicyclic of 5 to 10 carbon atoms.
Buckton teaches that incorporation of cyclic amino-acid residues into peptide structures was a known strategy for imposing conformational restriction and controlling molecular conformation. In particular, Buckton describes incorporation of cycloalanines into peptide structures and explains that conformational restriction reduces the number of conformations available to a molecule. Buckton additionally describes cyclo-alkane-containing tethers as structural elements useful for controlling peptide conformation (Pg. 1504-1505 and Figure 14.)
Therefore, it would have been prima facie obvious to one of ordinary skill in the art to modify the amino-acid-containing linker structure of the compounds claimed in the ‘792 application by incorporating a cyclic amino-acid residue having an alicyclic group, as taught by Buckton, because incorporation of such cyclic amino-acid structural elements was a known technique for imposing conformation restriction and controlling molecular conformation.
One of ordinary skill in the art would have had a reasonable expectation of success because the modification employs a known cyclic amino-acid structural variation within the intervening linker while retaining the respective target-binding, albumin-binding, and metal-chelating functional moieties of the ‘792 compounds.
Therefore, the presently claimed compounds constitute no more than an obvious variation of the compounds claimed in copending ‘792.
This is a provisional nonstatutory double patenting rejection.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 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
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