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 .
Election/Restrictions
Applicant’s election with traverse of Group I and species of formula (4) in the reply filed on May 11, 2026 is acknowledged.
The traversal is on the ground(s) that the present invention is considered to be non-obvious (having a special technical feature) because there is no motivation for a person skilled in the art to extend the methine chain of ICG (indocyanine green). Applicant mentions that Feng et al. do not teach or suggest the maintenance or improvement of emission efficiency and that the present invention exhibits an unexpected effect that deviates from the “general tendency”. Applicant also mentions that the compounds recited in claim 4 have highly similar structures to one another and examining these compounds collectively would not substantially increase the examination burden.
This is not found persuasive. As discussed in the Office Action mailed March 12, 2026, Feng teaches that the spectral distribution of cyanine dyes is related to the conjugation degree of the methine chain, and increasing the length of the methine chain can result in a red-shift of the absorption and emission spectrum. It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to extend the methine chain for use as a shortwave infrared (SWIR) fluorescent agent. 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 to tune absorption and emission wavelengths for specific purposes. Because Feng does not teach that increasing the length of the methine chain would negatively affect the emission efficiency (i.e., there is no teaching away), a person of ordinary skill in the art would have been motivated to increase the length for SWIR fluorescent agent. The “general tendency” stating that larger molecular structure with longer chain leads to reduced fluorescence emission efficiency cannot be applied as an absolute rule. Extending the chain-like structure can increase the π-conjugation length, which can enhance the molar extinction coefficient (the ability to absorb light). It is also possible that lengthening a molecule restricts molecular rotation and vibration. This restriction can suppress non-radiative decay and boosts fluorescence efficiency similar to the effects of structural rigidification or aggregation-induced emission effects. If the increase in intrinsic light-absorption and emission capability outweigh the energy lost, the efficiency will be maintained or improved. Therefore, framing the present invention as an unexpected effect that defied “general tendency” is an oversimplification. Regarding the species election, the claims are not drawn to a reasonable number of species, as the X of claim 1 encompasses any reactive crosslinking group with respect to a molecular recognition agent, rather than being limited to the specific examples in claim 4.
Drawings
FIG. 9 is objected to because there is no clearly identifiable, independent curve or line corresponding to the “Erbitux (1mg/mL)” label. The label points vaguely toward the bottom of the graph where multiple lines overlap, making it unclear where the curve for “Erbitux (1mg/mL)” starts or is located.
Appropriate correction is required.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Objections
Claim 4 is objected to because the claim fails to end with a period as required. Additionally, the claim lacks punctuation (e.g., commas or semicolons) between the recited formulas, and the claim lacks an appropriate coordinating conjugation (e.g., “and” or “or”) before the last formula.
Appropriate correction is required.
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); cited on PTO-892; all citations from the machine translation) in view of and Feng et al. (Organic & Biomolecular Chemistry, 2020).
Regarding claims 1-4, Zhang discloses a near-infrared (NIR) fluorescent imaging probe comprising GnRH (gonadotropin-releasing hormone) polypeptide and a fluorescent dye ICG-NHS (N-hydroxysuccinimide) (claim 1). Zhang discloses the structure of ICG-NHS
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(claim 1), which is substantially similar to that of the compound of formula (4) of instant claim 4 (elected species), differing only in the length of the methine chain (bridge) connecting the two heterocyclic compounds. The compound of formula (4) of instant claims has a longer methine chain (nonamethine/enneamethine cyanine, Cy9) than that of ICG-NHS of Zhang (heptamethine cyanine, Cy7). Regarding claims 5 and 6, Zhang discloses that the GnRH polypeptide (molecular recognition agent) can be bonded to the ICG-NHS via a residue of the reactive crosslinking group (NHS)
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and the GnRHa-ICG complex targets a GnRH receptor which is highly expressed in tumor cells (abstract; claim 1).
Zhang does not disclose compounds having methine chains of the same length (Cy9) as the methine chain of the compound of formula (4) of instant claims.
Feng discloses that the spectral distribution of cyanine dyes is related to the conjugation degree of the methine chain and that increasing the length of the methine chain by a single conjugated C=C double bond results in a red-shift of the absorption and emission spectra by about 100 nm (page 9385, column 1, ¶ 2 – column 2, ¶ 1).
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 SWIR region. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Feng teaches that cyanine dyes with longer methine chains exhibit higher absorption and emission wavelengths. 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 methine chain affects dye characteristics such as absorption and emission wavelengths, efficiency, solubility, and stability.
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; cited on PTO-892).
Zhang and Feng are discussed above.
Neither Zhang nor Feng discloses a SWIR fluorescent agent.
Carr discloses that commercially available NIR dyes such as the US Food and Drug Administration (FDA)-approved contrast agent ICG exhibit optical properties suitable for in vivo SWIR fluorescence imaging (abstract). Carr discloses that the use of ICG for SWIR imaging opens the potential for rapid translation of SWIR fluorescence imaging to humans in clinical applications because no FDA-approved fluorophores with peak emission in the SWIR yet exist (abstract).
It would have been obvious to a person of ordinary skill in the art before the effective
filing date of the claimed invention to utilize the compound of Zhang and Feng as a SWIR fluorescent agent, instead of a NIR fluorescent agent. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Carr teaches that ICG can be used for SWIR fluorescence imaging. Further, a person of ordinary skill in the art would have been motivated to utilize the compound of Zhang and Feng for SWIR imaging in order to expand the applications of the compound. As discussed above, increasing the length of the methine chain of ICG-NHS also makes the compound more suitable as a SWIR fluorescent agent.
Conclusion
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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/JONG HWAN BAEK/Examiner, Art Unit 1618
/Michael G. Hartley/Supervisory Patent Examiner, Art Unit 1618
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