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 II, claims 10-25 and 28-35, in the reply filed on 23 June 2026 is acknowledged. A preliminary amendment to the claims filed on 23 June 2026 is acknowledged. Claims 1-9, 26, and 27 have been canceled and claims 12, 14, 15, 18, 20-23, 25, 28, 30, 33, and 35 have been amended.
Drawings
The drawings are objected to for the following reasons.
Regarding Fig. 1a, in the right panel the data lines cannot be distinguished from one another.
Regarding Fig. 1c and 1d, the text is too small.
Regarding Fig. 3c, the data lines cannot be distinguished from one another. Possibly merely enlarging the graph would provide sufficient clarity.
Regarding Figs. 4a, 18a, and 18b, the color key for the signal provides the same grayscale shade for both the signal extremes of 1 and 0 (unlike the key in Fig. 5a).
Regarding Fig. 5b and 5c, the text is too small.
Regarding Fig. 10a, the color key for the electric field provides the same grayscale shade for both the extremes of 1 and 0.
Regarding Fig. 10b, the data lines cannot be distinguished from one another.
Regarding Fig. 11c, the data lines cannot be distinguished from one another and the text is too small. Perhaps the trend of the increasing or decreasing template diameter could be indicated with an arrow?
Regarding Fig. 15a, the data lines cannot be distinguished from one another. Perhaps the trend of the increasing or decreasing exosome count could be indicated with an arrow?
Regarding Fig. 16, the chemical structures are too small/illegible.
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.
Abstract
Applicant is reminded of the proper language and format for an abstract of the disclosure.
The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details.
The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. In addition, the form and legal phraseology often used in patent claims, such as “means” and “said,” should be avoided.
The abstract of the disclosure is objected to because it uses legal phraseology such as "said." A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
Claim Objections
Claims 10, 20, 28, and 35 are objected to because of the following informalities:
Regarding claims 10 and 28, the limitation "the nanoparticles or precursor" in step a) must be changed to "the nanoparticles or precursor thereof".
Regarding claim 20, there appear to be word(s) missing in the following limitation: "nanoparticles in excess required to form the nanoshell."
Regarding claim 35, the limitation "the one or more targets comprises" must be changed to "the one or more targets comprise."
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
Claims 10-25 and 28-35 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Independent claim 10 recites the limitation "one or more targets that are bound or associated with a nanovesicle in a sample" in the preamble. It is unclear whether this limitation should be interpreted as (A) one or more targets that are (i) bound or (ii) associated with a nanovesicle in a sample, or (B) one or more targets that are (i) bound with a nanovesicle in a sample or (ii) associated with a nanovesicle in a sample. According to interpretation A, the limitation "one or more targets that are bound" appears to be fragmentary. According to interpretation B, the limitation "one or more targets that are bound…with a nanovesicle in a sample" appears to be using the wrong word and does not make sense. This limitation is henceforth interpreted in this office action as "one or more targets that are bound to or associated with a nanovesicle in a sample." Claim 10 also recites "one or more targets that are bound or associated with the nanovesicle" in step a) that is indefinite for analogous reasons. Claim 25 recites "the one or more targets that are bound or associated with the nanovesicle." Independent claim 28 recites the limitations "one or more targets that are bound or associated with nanovesicles…" and "one or more targets that are bound or associated with the nanovesicle" that are indefinite for analogous reasons.
Independent claims 10 and 28 recite the limitation "sequentially or simultaneously contacting a sample with nanoparticles or a precursor thereof and one or more fluorescent molecular probes" in step a). It is unclear whether the scope of the limitation "sequentially… contacting a sample with [i] nanoparticles or a precursor thereof and [ii] one or more fluorescent molecular probes" is meant to encompass only contacting the sample with [i] first nanoparticles or a precursor thereof and [ii] second one or more fluorescent molecular probes." For purposes of evaluating the claims under 35 USC 112(a), this interpretation is applied, given that a step of sequentially contacting the sample with first one or more fluorescent molecular probes and second nanoparticles or a precursor thereof would not comply with 35 USC 112(a).
Independent claims 10 and 28 recite the limitation "the surface of said nanovesicle" in step a). There is insufficient antecedent basis for this limitation in the claims. A nanovesicle is not inherently characterized by a single surface, given that a nanovesicle can have both an inner surface and an outer surface.
Claim 10 recites the limitation "said nanovesicle" in step a). There is insufficient antecedent basis for this limitation in the claim. The claim previously introduces the limitation "a nanovesicle in a sample" in the preamble, while also introducing "a sample" in step a). Must the limitation "a sample" in step a) be the same as the preamble limitation? It is unclear whether the claim positively recites a step that requires a nanovesicle, as opposed to reciting steps that require functionality if such a nanovesicle is present. Dependent claims 14 and 25 also recite "the nanovesicle."
Claim 10 recites the limitation "wherein the nanoparticles or precursor [thereof] are capable of binding onto the surface of said nanovesicle and form, in situ, a nanoshell that surrounds said nanovesicle" in step a). The verbs in this limitation lack parallelism. It is unclear whether this limitation requires that the nanoparticles or precursor thereof are merely capable of binding to a surface of a nanovesicle (if such a nanovesicle is present) while also positively reciting an active step of forming a nanoshell that surrounds said nanovesicle. If a nanoshell must be formed in the method, what is the antecedent basis for said nanovesicle? [As previously noted, the limitation "a sample" introduced in step a) is not required to have a nanovesicle.] Claim 28 is indefinite for analogous reasons.
Claim 10 recites the limitation "wherein the one or more fluorescent molecular probes are capable of specifically binding to one or more targets that are bound or associated with the nanovesicle and provide a unique emitting fluorescence wavelength for each said target" in step a). The verbs in this limitation lack parallelism. It is unclear whether this limitation requires that the one or more fluorescent molecular probes are merely capable of specifically binding to one or more targets (if such one or more targets are present) while also positively reciting an active step of providing a unique emitting fluorescence wavelength for each said target, which implies that "each said target" [sic] must be present. Claim 28 is indefinite for analogous reasons.
Claim 10 recites the limitation "each said target" [singular] in steps a) and b). There is insufficient antecedent basis for this limitation in the claim. The claim previously introduces both "one or more targets that are bound or associated with a nanovesicle in a sample" in the preamble and "one or more targets that are bound or associated with the nanovesicle" in step a). Claim 28 is indefinite for analogous reasons.
Claim 10 recites the limitation "the emitted fluorescence" in step b). There is insufficient antecedent basis for this limitation in the claim.
Claim 10 recites the limitation "the one or more targets that are bound or associated with the nanovesicle" in step b). There is insufficient antecedent basis for this limitation because the claim previously introduces both "one or more targets that are bound or associated with a nanovesicle in a sample" in the preamble and "one or more targets that are bound or associated with the nanovesicle" in step a). Claim 25 is indefinite for analogous reasons.
Claim 10 recites the limitation "the detection" in step b). There is insufficient antecedent basis for this limitation in the claim. Claim 28 is indefinite for analogous reasons.
Dependent claims 11-25 and 29-35 are rejected for depending from indefinite claim 10 or 28.
Claim 11 recites the limitations "the optical properties," "the fluorescent molecular probes," and "the detection signal." There is insufficient antecedent basis for these limitations in the claim. Does the claim require plural fluorescent molecular probes, whereas independent claim 10 merely requires one or more fluorescent molecular probes?
Claim 12 recites the limitations "the optical properties" and "the fluorescent molecular probes." There is insufficient antecedent basis for these limitations in the claim. Does the claim require plural fluorescent molecular probes, whereas independent claim 10 merely requires one or more fluorescent molecular probes?
Claim 13 recites the limitation "the one or more targets." There is insufficient antecedent basis for this limitation in the claim. Claim 13 previously introduces both "one or more targets that are bound or associated with a nanovesicle in a sample" in the preamble and "one or more targets that are bound or associated with the nanovesicle" in step a).
Claim 19 recites the limitation "the metallic salt solution." There is insufficient antecedent basis for this limitation in the claim.
Claims 21 and 22 recite the limitation "the fluorescent molecular probe." There is insufficient antecedent basis for this limitation because claim 10 previously recites one or more fluorescent molecular probes.
Claim 22 recites the limitation "the fluorescent molecular probe is modified with branched fluorescence." The intended meaning of "branched fluorescence" is completely unclear. Moreover, it is completely unclear how a probe can be modified with fluorescence. While Fig. 16 identifies a chemical structure as being an "Aptamer with branched fluorescence (3 dyes)," this is a non-standard use of "fluorescence" and "branched fluorescence." Instead, what is illustrated in Fig. 16 is a branched molecule comprising three fluorophores. Where applicant acts as his or her own lexicographer to specifically define a term of a claim contrary to its ordinary meaning, the written description must clearly redefine the claim term and set forth the uncommon definition so as to put one reasonably skilled in the art on notice that the applicant intended to so redefine that claim term. Process Control Corp. v. HydReclaim Corp., 190 F.3d 1350, 1357, 52 USPQ2d 1029, 1033 (Fed. Cir. 1999). The term "fluorescence" / "branched fluorescence" is indefinite because the specification does not clearly redefine the term.
Claim 23 recites the limitation "the sample." There is insufficient antecedent basis for this limitation because claim 10 previously introduces "a sample" twice.
Claim 25 recites the limitation "the characterisation." There is insufficient antecedent basis for this limitation in the claim.
Claim 25 recites the limitation "the level [singular] of the one or more targets [singular or plural]." It is unclear what is meant by a singular level of plural targets.
Claim 28 recites the limitations "said nanovesicle" and "the nanovesicle" in step a). There is insufficient antecedent basis for this limitation in the claim.
Claim 28 recites the limitation "said vesicle" in step a). There is insufficient antecedent basis for this limitation in the claim.
Claim 28 recites the limitation "the absorbance and/or emitted fluorescence" in step b). There is insufficient antecedent basis for this limitation in the claim.
Claim 30 recites the limitation "the sample." There is insufficient antecedent basis for this limitation because claim 28 previously introduces "a sample" twice.
Claim 35 recites the limitation "the one or more targets." There is insufficient antecedent basis for this limitation in the claim. Claim 28 previously introduces both "one or more targets that are bound or associated with nanovesicles in a sample" in the preamble and "one or more targets that are bound or associated with the nanovesicle" in step a).
Allowable Subject Matter
Claims 10-25 and 28-35 would be allowable if rewritten or amended to overcome the rejection(s) under 35 U.S.C. 112(b), and any objections, set forth in this Office action.
The closest prior art of record is Braeckmans (US 2018/0372730; previously cited). In the closest embodiments, Braeckmans discloses fluorescently labelling exosomes ([0113], [0124]) and mixing the labeled exosomes with AuNPs ([0114], [0124]). However, in these embodiments, Braeckmans discloses removing non-incorporated dye ([0114]) or counting the number of fluorescent spots ([0124]), which teaches away from the claimed method, "wherein the detection involves identifying an enhanced fluorescence quenching of the unique emitted fluorescence for each said target." Elsewhere, Braeckmans contains general teachings regarding identifying exosomes in a label free ([0017]), which also teaches away from the method of the independent claims that requires one or more fluorescent molecular probes.
The prior art of Chen ("A paper-supported aptasensor based on upconversion luminescence resonance energy transfer for the accessible determination of exosomes," Biosensors and Bioelectronics 2018; newly cited) discloses detection of exosomes via luminescence quenching of green luminescent upconversion nanoparticles (abstract, Fig. 1). A detection probe attached to a gold nanorod binds to a surface of an exosome (Fig. 1), but the gold nanorods of Chen do not form a nanoshell that surrounds the exosome.
The prior art of Naasani (US 2018/0067121; newly cited) is a method of detecting exosomes using a plurality of quantum dot nanoparticles conjugated to ligands (abstract, Fig. 1).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MICHELLE ADAMS whose telephone number is (571)270-5043. The examiner can normally be reached M, T, Th, and F, 12-4 P.M.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lyle Alexander can be reached at (571) 272-1254. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MICHELLE ADAMS/ Examiner, Art Unit 1797
/JENNIFER WECKER/ Primary Examiner, Art Unit 1797
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