DETAILED ACTION
This Office action details a first action on the merits for the above referenced application No. Claims 1-20 are pending in this application.
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 35 USC 111(a) filing filed on 4 Jun. 2024 and a continuation in part of US application No. 18/640,169 filed on 19 Apr. 2024 (now US patent No. 12,440,585 B2) and claims benefit under 35 USC 119(e) to US provisional application No. 63/538,038 filed on 12 Sep. 2023.
Information Disclosure Statement
An information disclosure statement (IDS) has not been filed with the instant application.
Election/Restrictions
Applicant's election with traverse of Group I, claims 1-6, 9, and 17 in the reply filed on 17 Jun. 2026 is acknowledged. The traversal is on the ground(s) that a search for the agents of Group I would necessarily result in discovery of any of the methods in Groups II-V. The search and examination of groups can be made without undue burden on the Examiner. This is not found persuasive because the search of Groups II-V would require a different field of search at least by requiring the use of different search terms not related to the search of Group I. For example, the search of Group II would require searching for tumor cells or cells undergoing angiogenesis. Searching Group III would require searching for adult solid tumor cells or pediatric solid tumor cells. In these examples, the search of Group I would not be coextensive with Groups II and III.
The requirement is still deemed proper and is therefore made FINAL.
Claims 7-8, 10-16, and 18-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected Groups II-V, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 17 Jun. 2026.
Applicant’s election of species ((ZWI)4-DOTAM) in the reply filed on 17 Jun. 2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
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wherein Y= alkyl or reactive linking group, ZWI=sulphobetaine or an N-oxide group, R=H or alkyl group, and metal=Pb.
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.
Claim(s) 1-2, 4-6, 9, and 17 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kriemen et al. (Chem. Asian J.; published 2014; see attached 892), in view of Chappell et al. (Nucl. Med. Biol.; published 2000; see attached 892).
Kriemen et al. teach the synthesis of 1,4,7,10-tetra-azacyclododecan-1,4,7,10-tetra-azidoethylacetic acid (DOTAZA) and related clickable DOTA derivatives (see title). Kriemen et al. teach that DOTA is a gold standard chelator for may radiometal isotopes (pg. 2197). Kriemen et al. teach modular derivatives 5 and 5. Derivatives 5 which have fourfold symmetry allow the conjugation of four targeting vectors or other effectors (pg. 2198). Kriemen et al. teach compound 30
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(scheme 6). Kriemen et al. teach compound 37
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(scheme 8). With the addition of zwitterionic moieties in compound 37 to targeted DOTA derivatives, non-specific tissue binding may be impeded if the targeting vector is prone to non-specific protein adsorption (pg. 2201).
Kriemen et al. do not disclose a zwitterionic metal chelator complex comprising a metal chelator having one or more zwitterionic groups wherein the metal chelator is a derivative of DOTAM and optionally further comprising one or more targeting vectors and optionally wherein the metal is Pb such as203Pb and 212Pb for imaging and therapy and optionally wherein the chelator is (ZWI)4-DOTAM and optionally wherein the wherein the zwitterionic metal chelator complex is the elected species.
Chappell et al. teach the synthesis, characterization, and evaluation of novel bifunctional chelating agent for the lead isotopes 203Pb and 212Pb (see title). Chappell et al. teach TCMC
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(Fig. 1). Chappell et al. teach that one of the challenges to the use of the Pb(II) radionuclides is the issue of acid catalyzed dissociation of the radiometal from the ligand. The ligand based on the cyclen foundation with four carbamoyl methyl pendent arms (TCMC) rather than carboxylates has been found to form metal complexes that are exceptionally inert to metal ion release, including Pb(II). Replacement of the carboxylates with amides should then reduce the propensity for acid catalyzed dissociation of Pb(II) while providing a stable complex for this element (pg. 94). Chappell et al. teach that nearly quantitative labeling yields (>95%) were achieved in labeling of TCMC-CC49 with 203Pb (30 min at 37oC) considerably higher than typical yields for labeling of DOTA-CC49 with 203Pb (60-80%) at the same conditions (pg. 99). Isotope exchange experiments with the DOTA and TCMC ligands indicated that the Pb[TCMC]2+ complex was less labile to metal ion release than Pb[DOTA]2- at pH 3.5 and below. This result prompted us to synthesize a bifunctional TCMC and further evaluate its potential for use in RIT and RII. The TCMC ligand was found to have many other advantages over bifunctional DOTA ligand. Abrogation of the toxicity associated with the trafficking of 212Pb following cellular internalization and metabolic processes by the use of the TCMC-mAb conjugate might provide an increased range of potential therapeutic applications for this isotope as an in vivo generator of 212Bi (pg. 99). Chappell et al. teach an aqueous NH4OAc solution (pharmaceutically acceptable carrier).
It would have been obvious to a person of ordinary skill in the art before the effective filing date to modify the compound of Kriemen et al. (compound 30) so that the azide functionalities react to form a triazole conjugated sulphobetaine zwitterionic group and so that amide functionalities (CONH2) replace the carboxyl (CO2H) functionalities and so that that chelator chelates 203Pb or 212Pb to form a diagnostic or therapeutic agent in a pharmaceutically acceptable carrier as taught by Kriemen et al. and Chappell et al. because the zwitterionic sulphobetaine functionalities would have been expected to advantageously enable impeded non-specific tissue binding and because the amide functionalities and Pb complexes thereof would have been expected to advantageously enable stable radiolead complexes advantageously capable of theranostic SPECT imaging and radiotherapy.
Claim(s) 1-6, 9, and 17 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kriemen et al. (Chem. Asian J.; published 2014; see attached 892), in view of Chappell et al. (Nucl. Med. Biol.; published 2000; see attached 892), in further view of Choi et al. (Nat. Biotech.; published 2013; see attached 892).
Kriemen et al. teach as discussed above.
Kriemen et al. do not further teach wherein one or more targeting vectors are cRGD.
Chappell et al. teach as discussed above.
Choi et al. teach targeted zwitterionic near-infrared fluorophores for improved optical imaging (see title). Choi et al. teach that zw800-1 provides a much-improved SBR when targeted to cancer cells or proteins by conjugation with a cyclic RGD peptide, fibrinogen or antibodies. In tumor model systems, a tumor to background ratio of 17.2 is achieved at 4 h after injection of zw800-1 conjugated to cRGD compared to ratios of 5.1 with IRdye800-CW and 2.7 with Cy5.5 (see abstract).
It would have been obvious to a person of ordinary skill in the art before the effective filing date to further modify Kriemen et al. so that the obvious targeting vector is a cRDG targeting vector as taught by Kreimen et al. and Choi et al. because the cRGD targeting vector would have been expected to advantageously enable tumor imaging and radiotherapy having much impeded non-specific binding.
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 1-6, 9, and 17 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of U.S. Patent No. 12,440,585 B2, in view of Chappell et al. (Nucl. Med. Biol.; published 2000; see attached 892).
Claims 1-9 of U.S. Patent No. 12,440,585 B2 claim a zwitterionic metal chelator complex wherein the metal chelator is of formula (ZWI)4-DOTA
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or
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optionally further comprising a targeting vector such as cRGD and wherein the metal of the metal complex is Pb and imaging agent and a zwitterionic chelator thereof.
Claims 1-9 of U.S. Patent No. 12,440,585 B2 do not claim a zwitterionic metal chelator complex wherein the metal chelator is a derivative of DOTAM or of formula (ZWI)4-DOTAM.
Chappell et al. teach as discussed above.
It would have been obvious to a person of ordinary skill in the art before the effective filing date to modify claims 1-9 of U.S. Patent No. 12,440,585 B2 so that the metal chelator is a derivative of DOTAM to form a diagnostic or therapeutic agent in a pharmaceutically acceptable carrier as taught by Chappell et al. because the derivative of DOTAM would have been expected to advantageously enable the formation of stable Pb complexes (203Pb and 212Pb) in high radiochemical yield suitable for imaging and therapy.
Claims 1-6, 9, and 17 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-35 of copending Application No. 19/659,708, in view of Kriemen et al. (Chem. Asian J.; published 2014; see attached 892), and Chappell et al. (Nucl. Med. Biol.; published 2000; see attached 892). This is a provisional nonstatutory double patenting rejection.
Claims 1-35 of copending Application No. 19/659,708 claim a zwitterionic metal chelator complex comprising a metal chelator having one or more zwitterionic groups and a metal or metal isotope selected from radionuclide, a label, a paramagnetic metal and a heavy metal optionally further comprising one or more targeting vectors such as cRGD and an imaging agent or therapeutic agent thereof.
Claims 1-35 of copending Application No. 19/659,708 do not claim a zwitterionic metal chelator complex wherein the metal chelator is a derivative of DOTAM a optionally wherein the metal is Pb and optionally wherein the chelator is (ZWI)4-DOTAM and optionally wherein the wherein the zwitterionic metal chelator complex is the elected species optionally further comprising a pharmaceutically acceptable carrier.
Kriemen et al. teach as discussed above.
Chappell et al. teach as discussed above.
It would have been obvious to a person of ordinary skill in the art before the effective filing date to modify claims 1-35 of copending Application No. 19/659,708 so that the metal chelator is derivative of DOTAM and the elected species wherein the metal is Pb to form a diagnostic or therapeutic agent in a pharmaceutically acceptable carrier as taught by Kriemen et al. and Chappell et al. because the derivative of DOTAM would have been expected to advantageously enable stable Pb complexes prepared in high radiochemical yield and suitable for imaging and radiotherapy with non-specific binding significantly impeded.
Claims 1-6, 9, and 17 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8, 13-15, 20-21, 23-25, and 27-30 of copending Application No. 19/558,087, in view of Kriemen et al. (Chem. Asian J.; published 2014; see attached 892), and Chappell et al. (Nucl. Med. Biol.; published 2000; see attached 892). This is a provisional nonstatutory double patenting rejection.
Claims 1-8, 13-15, 20-21, 23-25, and 27-30 of copending Application No. 19/558,087 claim a zwitterionic metal chelator complex comprising a metal chelator having one or more zwitterionic groups and a metal or metal isotope selected from radionuclide, a label, a paramagnetic metal and a heavy metal optionally further comprising one or more targeting vectors such as cRGD and an imaging agent or therapeutic agent thereof.
Claims 1-8, 13-15, 20-21, 23-25, and 27-30 of copending Application No. 19/558,087 do not claim a zwitterionic metal chelator complex wherein the metal chelator is a derivative of DOTAM a optionally wherein the metal is Pb and optionally wherein the chelator is (ZWI)4-DOTAM and optionally wherein the wherein the zwitterionic metal chelator complex is the elected species optionally further comprising a pharmaceutically acceptable carrier.
Kriemen et al. teach as discussed above.
Chappell et al. teach as discussed above.
It would have been obvious to a person of ordinary skill in the art before the effective filing date to modify claims 1-8, 13-15, 20-21, 23-25, and 27-30 of copending Application No. 19/558,087 so that the metal chelator is derivative of DOTAM and the elected species wherein the metal is Pb to form a diagnostic or therapeutic agent in a pharmaceutically acceptable carrier as taught by Kriemen et al. and Chappell et al. because the derivative of DOTAM would have been expected to advantageously enable stable Pb complexes prepared in high radiochemical yield and suitable for imaging and radiotherapy with non-specific binding significantly impeded.
Claims 1-6, 9, and 17 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of copending Application No. 19/266,463 in view of Kriemen et al. (Chem. Asian J.; published 2014; see attached 892), and Chappell et al. (Nucl. Med. Biol.; published 2000; see attached 892). This is a provisional nonstatutory double patenting rejection.
Claims 1-14 of copending Application No. 19/266,463 claim a zwitterionic metal chelator complex comprising a metal chelator having one or more zwitterionic groups and a metal or metal isotope selected from radionuclide, a label, a paramagnetic metal and a heavy metal optionally wherein the metal is Pb-212 optionally further comprising one or more targeting vectors such as cRGD and an imaging agent or therapeutic agent thereof.
Claims 1-14 of copending Application No. 19/266,463 do not claim a zwitterionic metal chelator complex wherein the metal chelator is a derivative of DOTAM a optionally wherein the metal is Pb and optionally wherein the chelator is (ZWI)4-DOTAM and optionally wherein the wherein the zwitterionic metal chelator complex is the elected species optionally further comprising a pharmaceutically acceptable carrier.
Kriemen et al. teach as discussed above.
Chappell et al. teach as discussed above.
It would have been obvious to a person of ordinary skill in the art before the effective filing date to modify claims 1-14 of copending Application No. 19/266,463 so that the metal chelator is derivative of DOTAM and the elected species wherein the metal is Pb to form a diagnostic or therapeutic agent in a pharmaceutically acceptable carrier as taught by Kriemen et al. and Chappell et al. because the derivative of DOTAM would have been expected to advantageously enable stable Pb complexes prepared in high radiochemical yield and suitable for imaging and radiotherapy with non-specific binding significantly impeded.
Conclusion
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/Michael G. Hartley/Supervisory Patent Examiner, Art Unit 1618
/SEAN R. DONOHUE/
Examiner, Art Unit 1618
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