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 September 9, 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 September 9, 2026, the issues identified in the June 16, 2026 Office Action have been fully resolved. Therefore, the drawings received on September 9, 2026 are acceptable.
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 1-6 are rejected under 35 U.S.C. 103 as being unpatentable over Zhang (张) et al. (CN 2019 10418685 (CN 110075322)) in view of Feng et al. (Organic & Biomolecular Chemistry, 2020).
This rejection is MAINTAINED for the reasons of record set forth in the Office Action mailed June 16, 2026 and those set forth herein.
The declaration under 37 CFR 1.132 filed September 9, 2026 is insufficient to overcome the rejection of claims 1-7 based upon Zhang, Feng, and Carr under U.S.C. 103 as set forth in the last Office action because 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 POSITA would have reasonably anticipated. As discussed in the Office Action mailed June 16, 2026, Feng teaches that cyanine dyes with longer methine chains exhibit higher absorption and emission wavelengths. It would have been obvious that extending the methine chain can make the absorption and emission wavelengths shift into the SWIR region and provide suitable properties for SWIR imaging. A POSITA would readily recognize that modifying molecular structure, such as extending the conjugation length of cyanine dyes, often involves routine trade-offs among photophysical properties like quantum yield, extinction coefficient, and emission wavelength. Recognizing and accepting these expected, inherent structural consequences during routine optimization do not confer patentability or render the resulting properties unexpected. Further, a POSITA would be motivated to adjust the length of the methine chain to optimize fluorescent agents for specific applications, as chain length affects overall characteristics including absorption, emission, efficiency, solubility, and stability. Because the general effects of methine chain extension are well-documented in the art achieving operative brightness and functionality within the targeted SWIR region represents an expected result of routine chain elongation and optimization, rather than an unpredictable or surprising technical breakthrough. The results in the Declaration merely demonstrate that modifying (extending) the methine chain to fine-tune physical performance produces predictable, incremental changes rather than unexpected differences in kind.
Second, Applicant fails to provide a direct comparison with the closest prior art (Zhang, Feng, and Carr 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 (such as at least ICG-C7). 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 Zhang, Feng, and Carr, the showing is insufficient to rebut the prima facie case of obviousness. Applicant cannot establish unexpected results merely by comparing the claimed formulation against inferior or no-prior art simple control formulations (such as ICG).
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. Claim 1 encompasses large numbers of various compounds. However, Applicant’s arguments rely on narrow, specific examples such as ICG-C9 and ICG-C11. Applicant fails to provide examples of additional combinations between methine chain length and any reactive crosslinking group with respect to a molecular recognition agent. The limited experimental data do not establish that the entire claimed genus would exhibit the same allegedly unexpected properties.
Applicant argues that Feng does not prepare or describe the presently claimed Cy9 compound and does not address whether extending the methine chain of ICG-NHS would provide a compound suitable for practical SWIR fluorescence imaging. Applicant argues that Feng does not establish that extending the methine chain of Zhang's ICG-NHS would predictably retain sufficient fluorescence efficiency, brightness, stability, and aqueous compatibility for SWIR bioimaging. Applicant argues that neither Zhang nor Feng provides a reasonable expectation of obtaining the combination of properties demonstrated in Jin’s Declaration and Reference Document. Applicant argues that the Office Action does not identify any teaching that would have led a POSITA to replace Zhang's GnRH polypeptide with the antibody or antigen- binding antibody fragment required by claim 6.
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. One cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references.
As discussed in the Office Action mailed June 16, 2026, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the ICG-NHS of Zhang by extending the methine chain (Cy9 instead of Cy7) in order to shift the absorption and emission wavelengths into the SWIR region because Feng teaches that cyanine dyes with longer methine chains exhibit higher absorption and emission wavelengths. Feng expressly teaches that the spectral distribution of cyanine dyes relates to the conjugation degree of the methine chain, wherein increasing the length by a single conjugated double bond results in a red-shift of absorption and demission spectra by about 100 nm. Further, a person of ordinary skill in the art would have been motivated to adjust the length of the methine chain in a cyanine dye in order to optimize the fluorescent agent for specific purposes, as the length of the methine chain affects dye characteristics such as absorption and emission wavelengths, efficiency, solubility, and stability. Because Feng and other references do not teach that increasing the length of the methine chain would negatively affect the emission efficiency, a POSITA would have been motivated to increase the length for a SWIR fluorescent agent. There is nothing in the cited references that disparages, discourages, or teaches away from extending the methine chain for SWIR applications. Rather, a POSITA would recognize that the length of the methine chain affects properties such as absorption/emission wavelengths, efficiency, solubility, and stability. Adjusting these parameters to optimize fluorescent agents for specific purposes represents routine optimization with a reasonable expectation of success. Further, claims 1-7 are directed to a compound per se (a structural product claim). Whether the claimed compound is intended or optimized for SWIR imaging does not confer patentability or distinguish the claimed structure over the prior art. Absent a structural difference, a statement of intended use, technical advantage, or field of application recited in a product claim does not patentably distinguish the claimed compound from a prior art compound that possesses the same chemical structure or would have been obvious to arrive at based on structural modifications suggested by the prior art. As discussed above, Zhang in view of Feng renders the claimed compound obvious. Accordingly, Applicant’s recitation of SWIR bioimaging capabilities cannot impart nonobviousness to an otherwise obvious chemical compound. Zhang discloses that the GnRH polypeptide can serve as a molecular recognition agent and that the GnRHa-ICG complex targets a GnRH receptor which is highly expressed in tumor cells. Further, it is well established to attach a targeting moiety for targeted therapy and diagnostics. A POSITA would select a specific targeting moiety such as specific polypeptide, antibody, or antibody fragment according to the specific requirement of the intended application.
Applicant’s assertions of unexpected results fail to satisfy the requisite legal criteria established under MPEP § 716.02. See the response to the Declaration above.
Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over Zhang and Feng as applied to claims 1-6 above, and further in view of Carr et al. (Proceedings of the National Academy of Sciences, 2018).
This rejection is MAINTAINED for the reasons of record set forth in the Office Action mailed June 16, 2026 and those set forth herein.
Applicant argues that Carr does not cure the deficiencies of Zhang and Feng with respect to claim 7. Applicant argues that the objective evidence instead establishes that the claimed compounds and complexes provide selectively excitable SWIR fluorescence suitable for multiplexed and targeted biological imaging, which are properties not taught or reasonably predicted by Zhang, Feng, or Carr.
This argument is unpersuasive. Reliance on the teachings of Carr demonstrates that the FDA-approved contrast agent ICG exhibits optical properties suitable for in vivo SWIR fluorescence imaging. As discussed above, Zhang in view of Feng already teaches the claimed compound and that increasing the length of the methine chain of ICG-NHS makes the compound more suitable as a SWIR fluorescent agent. As discussed above, Applicant has not provided sufficient objective evidence to demonstrate unexpected results.
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.
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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
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