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 without traverse of group I, fluorescein pentyl dicarbonate, in vitro and corneal endothelial cells in the reply filed on May 28, 2026 is acknowledged.
The requirement is still deemed proper and is therefore made FINAL.
Specification
The disclosure is objected to because of the following informalities: the quality of multiple structures of the specification as filed is low as shown by the numerous (?) in the PGPub of the instant application that indicate missing or illegible text.
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.
Claim(s) s 1 – 6, 8, 9, 15 – 17, 19 and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Figueira et al. (Exp Eye Res, 2018) in view of Yue et al. (Anal Chem, 2019).
Figueira et al. discloses that given the main origin of noradrenaline (NA) in the cornea is neuronal in origin, the physiological determinates of release and correlation of functional findings with sympathetic nerve density and overall topography (abstract). Noradrenaline was particularly identified in the endothelium and epithelium portion of human corneal lamellar sections (abstract). A radiolabeled (tritiated) noradrenaline was added and superfusion fluid was collected at various time points (p 122, col 2, ¶¶ 4 and 5). As shown in Figures 1 and 2, the change in amount of radiolabel NA was determined to monitor NA in response to various conditions. Nerve morphology was studied using immunofluorescence staining and confocal microscopy observation (p 123, col 1, ¶ 3) so the fluorescence in these in vitro samples would be observable.
The use of dicarbonate fluorescin compound of formula (I) of the instant claims is not disclosed.
Yue et al. discloses a fluorescent probe to detect and visualize noradrenaline over dopamine and epinephrine in brain directly with comparable specificity to the noradrenaline synzyme immunofluorescence labeling path (abstract). The 2-amino ethanol moiety of noradrenaline react with fluorophore coupling carbonic ester via cascade nucleophilic substitution to form a 5 membered ring with the release of fluorophore, promoting probe specificity towards noradrenaline over other generic amines, dopamine and norepinephrine (p 2256, col 1, ¶ 2). Homologs of the compound labeled “FHE” in figure 2 falls within the scope of the instant formula (I) as FHE would require R1 to be a C2 alkyl and the lower limit of the instant claims is a C3 alkyl.
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to use a dicarbonate fluorescein containing compounds such as a homolog of FHE to measure noradrenaline in the corneal samples of Figueira et al. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because measurement of noradrenaline in corneal tissue is disclosed by Figueira et al. but uses tritiated noradrenaline to quantify the amount of noradrenaline. Use of fluorescent compounds such as those in Yue et al. will permit imaging of noradrenaline in the tissue sample or an alternative detection means for noradrenaline other than using radioactive isotopes as used by Figueira et al. Homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties (MPEP 2144.09) and there is no evidence of record as to the criticality of the alkyl chain length.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Nissa M Westerberg whose telephone number is (571)270-3532. The examiner can normally be reached M - F 8 am - 4 pm.
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/Nissa M Westerberg/Primary Examiner, Art Unit 1618
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