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 14, 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.
Drawings
Applicants amended the drawings filed August 14, 2026, the issues identified in the May 5, 2026 Office Action have been fully resolved. Therefore, the drawings received on August 14, 2026 are acceptable and the amendments are entered.
Specification
Applicants amended the specification filed August 14, 2026, the issues identified in the May 5, 2026 Office Action have been resolved. Therefore, the specification received on August 14, 2026 are 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 1-3, 12, 15, 30, 31, 35, 40, 42, 43, and 46-48 are rejected under 35 U.S.C. 103 as being unpatentable over Benesova et al. (WO 2018 215627; cited on IDS filed November 21, 2023) in view of Anderson et al. (Bioorganic and Medicinal Chemistry, 2007).
This rejection is MAINTAINED for the reasons of record set forth in the Office Action mailed May 5, 2026 and those set forth herein.
Regarding amended claim 1, Benesova does not disclose the glutamate residue (R3) is linked through an α-peptide bond,
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. However, Benesova in view of Anderson renders the amended claim 1 obvious like the claims 46-48 (177Lu-HTKO1169) as discussed in the Office Action mailed May 5, 2026.
Applicant argues that Anderson provides no motivation or expectation of success regarding pharmacokinetics upon changing to an α-linkage. Applicant argues that the α-linked compound has a surprising advantage over the γ-linked compound.
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. A reference does not need to explicitly teach or predict every specific downstream pharmacokinetic advantage to establish a prima facie case of obviousness. It is sufficient that the prior art provides a general motivation to modify the structural linkage to optimize binding parameter. Once a POSITA is motivated to make the structural modification, any resulting quantitative optimization in biological behavior such as clearance and tissue uptake inherently flow from that routine modification. Anderson explicitly teaches that the changing the glutamate residue linkage between α- and γ-positions alters binding affinity and metabolic stability. A POSITA would readily understand that altering metabolic stability directly dictates how quickly a compound is metabolized and cleared from the blood, while altering binding affinity directly impacts target retention and tumor uptake. Further, given that glutamate presents only two structural linkage options, testing the α-linkage to improve binding characteristics was obvious to try. Because the references do not discourage, criticize, or teach away from utilizing an α-linkage and presents a finite number of established structural options, a POSITA would have a reasonable expectation that utilizing an α-linkage would successfully alter the compound’s profile. Patentability is evaluated based on the claimed subject matter itself, not the subjective intent or specific clinical motivation of Applicant. Since the claimed molecule is structurally obvious over Benesova and Anderson, the resulting compound along with all of its inherent pharmacokinetic properties is unpatentable.
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. As discussed above, changes in blood clearance and tumor accumulation are not unexpected or isolated phenomena, but they are the inherent, predictable technical consequences of modifying binding affinity and stability as taught by Anderson. Accordingly, Applicant represents a predictable quantitative improvement (a matter of degree) rather than an entirely new, unexpected results in kind.
Second, Applicant fails to provide a direct comparison with the closest prior art (Benesova and Anderson 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 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 Benesova and Anderson, 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 46 encompass chemical compounds with variables including chelators and radiometals However, Applicant’s arguments rely on narrow, specific examples such as HTK01160 and HTK01190, which do not include a chelator and radiometal. Applicant fails to provide examples of more variable claimed structures. 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. 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.
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/JONG HWAN BAEK/Examiner, Art Unit 1618
/Michael G. Hartley/Supervisory Patent Examiner, Art Unit 1618
