DETAILED ACTION
This Office action details a final action on the merits for the above referenced application No. Claims 1-8 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 .
Status of Claims
Claims 1 and 3 are amended. Claim 9 is cancelled.
Response to Amendment
The amendments filed on 25 Nov. 2025 have been entered.
Response to Arguments
In view of Applicants amendments, the rejection of claims 1 and 3 because of minor informalities is withdrawn.
In view of Applicants amendments, the rejection of claims 1-9 under 35 USC 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter is withdrawn.
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, and 3-8 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kriemen et al. (Chem. Asian J.; published 2014), in view of Li et al. (Chem. Rev.; published 6 Oct. 2022) and Henry et al. (J. Label Compd Radiopharm.; published 2017) for the reasons cited in the Office action filed on 28 Aug. 2025.
Claim(s) 1-8 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kriemen et al. (Chem. Asian J.; published 2014), in view of Li et al. (Chem. Rev.; published 6 Oct. 2022) and Henry et al. (J. Label Compd Radiopharm.; published 2017), in further view of Choi et al. (Nat. Biotech.; published 2013) for the reasons cited in the Office action filed on 28 Aug. 2025.
Applicants Arguments
Applicants assert that nothing in Kriemen alone or in combination with Li, Henry, or Choi would lead one of ordinary skill to at a DOTA based metal chelator having three N-oxide zwitterionic groups without undue experimentation. Kriemen’s compound 30 contains four azide groups which is structurally distinct from the claimed formula with three N-oxide zwitterionic groups and one reactive group. Nothing in Li teaches or suggests the use of N-oxide zwitterionic groups as a group bound to or decorating a metal chelator such as DOTA. Nothing in Li teaches or suggests any way in which N-oxide based zwitterionic groups can be applied to other compounds with any reasonable expectation of success. Henry and Choi do not disclose or suggest the specific DOTA derivative formula with three N-oxide zwitterionic groups. There would have been no reason to make the specific structural modifications from Kriemen’s four-azide compound 30 without undue experimentation.
Applicant's arguments filed 25 Nov. 2025 have been fully considered but they are not persuasive. Kriemen provides compounds 5
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and 30
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that read in part on a compounds of the claimed formula wherein Y and W are methyl or ethyl linking groups and X is an azide reactive group. At scheme 1, Kriemen exemplifies attaching a similar chelator to single targeting vector by click reaction using an azide functionality. At scheme 8 and compound 37, Kriemen exemplifies the formation of a zwitterionic chelator having one arm amenable to conjugation of a targeting vector and three arms converted to zwitterion ionic groups at precursor azide functionalities. At pg. 2201, Kriemen teaches that with the addition of three zwitterionic moieties in compound 37 to targeted DOTA derivatives, non-specific tissue binding may be impeded if the target vector is prone to non-specific protein adsorption. From Kreimen alone, it would have been obvious to a person of ordinary skill in the art before the effective filing to modify compounds 5 and 30 in Kriemen by simply converting three of azide functionalities to zwitterionic functionalities while keeping one one azide functionality for conjugation to a targeting vector optionally by click reaction because that zwitterionic chelator would have been expected to enable a derivative chelator capable of impeding non-specific binding of targeting moieties prone to non-specific binding. Li teaches and motivates the N-oxide zwitterionic functionality as an advantageous alternative to the sulfobetaine zwitterionic functionality exemplified in Kriemen. A person of ordinary skill in the art would have been known how to reduce azide functionalities to amines that are readily convertible to TMAO N-oxide groups. Accordingly, a person of ordinary skill in the art could have used the compound 5 and 30 in Kriemen to arrive at the claimed compounds without substantial reconstruction. Li teaches that the TMAO N-oxide functionality impedes non-specific protein adsorption and are attractive for drug applications. Hydration ability and non-fouling properties increase with the decrease of CSL between cationic and anionic moieties. The TMAO N-oxide directly attaches the cationic and anionic moieties to each other which is understood to result in optimal hydration ability and non-fouling properties. A recognized advantage is the strongest reason to combine. It would have been obvious to a person of ordinary skill in the art before the effective filing date to modify the compounds of Kriemen by converting three of the azide functionalities to TMAO N-oxide zwitterionic functionalities as taught by Kriemen and Li because the three TMAO N-oxide zwitterionic functionalities would have been expected to enable optimal hydration ability and an optimal reduction of 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 1-8 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 Kriemen et al. (Chem. Asian J.; published 2014) for the reasons cited in the Office action filed on 28 Aug. 2025. Note that co-pending Application No. 18/640,169 has converted to the above patent.
Claims 1-8 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of copending Application No. 18/732,982, in view of Kriemen et al. (Chem. Asian J.; published 2014) and Li et al. (Chem. Rev.; published 6 Oct. 2022) for the reasons cited in the Office action filed on 28 Aug. 2025. This is a provisional nonstatutory double patenting rejection.
Applicants Arguments
Applicants request reconsideration of the double patenting rejections in view of the amendments and arguments made above.
Applicant's arguments filed 25 Nov. 2025 have been fully considered but they are not persuasive. The claims of the ‘585 patent claim a zwitterionic metal chelator comprising a metal chelator having the formula
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. As discussed above, Kriemen teaches and motivates attaching zwitterionic metal chelator complexes to targeting vectors using a reactive moiety at the position of the above N-oxide group. It would have been obvious to a person of ordinary skill in the art before the effective filing date to modify the claims of the ‘585 patent so that a reactive moiety suitable for conjugation replaces one N-oxide functionality because that zwitterionic chelator complex would have been expected to advantageously enable conjugation to a targeting vector such that the advantageous conjugation impedes none specific binding of the targeting vector while enabling imaging and therapy.
The claims of co-pending application No.18/732,982 claim (ZWI)3-DOTAM-X
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wherein Y=W= linking groups, and X is a reactive group. Kriemen teaches and motivates zwitterionic DOTA complexes having sulfobetaine zwitterionic groups. As discussed above, Li teaches the TMAO N-oxide group as an advantageous alternative to the sulfobetaine zwitterionic group. It would have been obvious to a person ordinary skill in the art before the effective filing date to modify the claims of co-pending application No. 18/732,982 so that the DOTAM is a DOTA and so that the ZWI groups are TMAO N-oxide ZWI groups as taught by Kriemen and Li because that chelator complex would have been expected to provide an equivalent zwitterionic chelator complex advantageously having good solubility and low non-specific binding.
Conclusion
THIS ACTION IS MADE FINAL. 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 SEAN R DONOHUE whose telephone number is (571)270-7441. The examiner can normally be reached on Monday - Friday, 8:00 - 5:00 EST.
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/SEAN R. DONOHUE/
Examiner, Art Unit 1618
/Michael G. Hartley/Supervisory Patent Examiner, Art Unit 1618