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 .
Response to Arguments
Applicant's arguments, filed August 3, 2026, have been fully considered but they are not deemed to be fully persuasive. The following rejections and/or objections constitute the complete set presently being applied to the instant application.
Specification
Applicant amended the specification filed August 3, 2026. The issues identified in the Office Action mailed May 1, 2026 have been fully resolved. Therefore, the substitute specification received on August 3, 2026 is acceptable and the amendments are entered.
Claim Rejections - 35 USC § 103
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 1, 2, 5, 8-10, 12, 13, 15, 16, 18-20, and 22 are rejected under 35 U.S.C. 103 as being unpatentable over Powell et al. (WO 2020 219715; cited on cited on IDS filed June 20 2023 and December 10, 2025) in view of Verhoeff et al. (European Journal of Nuclear Medicine and Molecular Imaging 2019).
This rejection is MAINTAINED for the reasons of record set forth in the Office Action mailed May 1, 2026 and those set forth herein.
Regarding new limitations of amended claims 1 and 12, the linker group comprises one or more amino acids, this limitation is derived from amended claim 16 and the claim 16 was rejected over Powell as discussed in the Office Action mailed May 1, 2026.
Applicant argues that neither Powell nor Verhoeff discloses or suggests an amino acid linker between two chelating ligands. Applicant argues that the disclosure of Powell describes lysine as a conjugation site for a DOTA reagent, not as a chemical linker component between two chelating ligands. Applicant argues that a person with ordinary skill in the art would not have been motivated to prepare a specific compound as claimed. Applicant argues that a person with ordinary skill in the art would not have been motivated to use amino acid linker between DFP and DOTA because Jowanaridhi et al (2017, IDS filed December 20, 2025) teaches only direct DFP-DOTA, details failed DFP-DOTA conjugate synthesis, and suggests macrocycle-based multi-DFO.
This argument is unpersuasive. The examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. The test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. Obviousness does not require a single reference to teach every feature when multiple references are combined.
As discussed in the Office Action mailed May 1, 2026, Powell explicitly teaches dual-chelator compounds (DFO and DOTA) connected via a linker, as well as the use of lysine to form covalent linkages with amine-reactive DOTA derivatives. While Powell illustrates the lysine residue as part of a protein targeting moiety, a POSITA would recognize that the lysine serves the exact same chemical function (amine-based covalent conjugation) regardless of whether it is positioned on the targeting protein or incorporated into the chemical linker between the two chelators. Moving a functional moiety like lysine from a targeting protein to an adjacent linker is a simple change of location of a known element without changing its fundamental chemistry property, yielding no unexpected results. Moreover, the use of lysine as a flexible, biocompatible amino acid spacer or linker is well-known and conventional in the art of bioconjugation. Applying or incorporating a known amino acid residue such as lysine into the linker framework constitutes a routine design choice according to the specific requirements of the application such as biocompatibility and biodistribution, and represents a simple structural modification of known elements according to their established function. Replacing generic alkyl linkers with a known, biocompatible amino acid spacer like lysine is a predictable substitution that requires no inventive step. Both Powell and Verhoeff reside in the same field of endeavor, namely radio-conjugated compounds for theranostic and imaging applications. Combining Powell’s dual-chelator system with Verhoeff’s validated targeting moiety represents a predictable combination to expand diagnostic and therapeutic utility for target specific theranostic applications, as discussed in the Office Action mailed May 1, 2026. Regarding Jowanaridhi’s disclosures of specific failed synthetic attempts do not constitute a “teaching away” from the entire class of amino acid linked dual chelators. Disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments. Furthermore, 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. A POSITA seeking to optimize chemical linkers and conjugation yield would be motivated to introduce flexible, biocompatible amino acid spacers such as lysine to overcome steric hindrance and synthetic limitations.
Applicant argues that the amino acid linker provides several unexpected technical advantages.
This argument is unpersuasive. Applicant’s assertions of unexpected results fail to satisfy the requisite legal criteria established under MPEP § 716.02. Objective evidence of unexpected results must be supported by an appropriate evidentiary showing, direct comparative data, and must be commensurate in scope with the claims. Applicant has failed to meet this burden based on the following criteria.
First, the alleged results are predictable, not truly unexpected. To establish unexpected results, the improvement or enhancement must significantly exceed what a person having ordinary skill in the art would have reasonably anticipated. The room-temperature reaction kinetics and biocompatibility are predictable technical results associated with incorporating amino acid linkers into bioconjugate chemistry. Because amino acid spacers are well known to enhance aqueous solubility and reduce steric interference, their implementation here yields expected functional outcomes. They represent predictable results that were anticipated by the prior art. The expected difference in degree of change, rather than unexpected differences in kind is insufficient to demonstrate nonobviousness.
Second, Applicant fails to provide a direct comparison with the closest prior art (Powell and Verhoeff individually or in a baseline combination). The evidence of unexpected results must involve a direct, side-by-side comparison between the claimed invention and the closest prior art. Without comparative data evaluating the claimed amino acid linker directly against the closest prior art reference, the record lacks a proper evidentiary baseline. Without a direct comparison showing that the actual performance of the claimed composition is significantly better than what would be predicted from a simple additive effect of Powell and Verhoeff, the showing is insufficient to rebut the prima facie case of obviousness.
Third, the results are not commensurate in scope of the claims. To effectively rebut a rejection of obviousness, the disclosure or evidence of unexpected results must be commensurate in scope with the claims to which the evidence is applied. Claims 1 and 12 encompass one or more broad categories or kinds of amino acids. However, Applicant’s arguments rely on narrow, specific examples such as lysine. Testing a single amino acid species fails to provide adequate factual support for the full scope of a broad genus claim. Applicant fails to provide examples of broader combinations of one or more amino acids. The limited experimental data does not establish that the entire claimed genus would exhibit the same allegedly unexpected properties.
Further, arguments or conclusory statements in the remarks section of a response do not take the place of evidence in the record. Allegations of unexpected results must be explicitly set forth in the originally filed specification or presented in a formal, signed declaration/affidavit accompanied by actual data. Attorney arguments cannot supply factual deficiencies in the evidentiary record. Absent the submission of such proper objective evidence, Applicant’s remarks remain mere unsubstantiated allegations that cannot overcome the rejection. Attorney arguments cannot serve as a substitute for comparative test data showing unexpected results.
Accordingly, because the combination of teachings would have been obvious to one of ordinary skill in the art, and because the Applicant has not provided sufficient objective evidence to demonstrate unexpected results, the rejection is maintained.
Conclusion
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 JONG HWAN BAEK whose telephone number is (571)272-0670. The examiner can normally be reached Mon - Thu, 9 am - 3 pm ET.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Michael G Hartley can be reached at 571-272-0616. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/JONG HWAN BAEK/Examiner, Art Unit 1618
/Michael G. Hartley/Supervisory Patent Examiner, Art Unit 1618
Prosecution Insights