DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on June 15, 2026 has been entered.
Status of the Claims
Claims 1, 3, 5 and 19-20 were pending. Claims 4, 6-11 and 16-17 were withdrawn.
Claim 1 is amended.
Claims 1, 3, 5 and 19-20 are examined herein.
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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
Determining the scope and contents of the prior art.
Ascertaining the differences between the prior art and the claims at issue.
Resolving the level of ordinary skill in the pertinent art.
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, 5, and 19-20 are rejected under 35 U.S.C. 103 as being unpatentable over Lee et al. (PGPub 2010/0009432) in view of Springer et al. (Anal Bioanal Chem. 2012 Dec;404(10):2869-75), Amama et al. (J Clin Endocrinol Metab. 1998 Feb;83(2):333-8), Ling et al. (Anal Chem. 2009 Feb 15;81(4):1707-14), and Ongagna-Yhombi et al. (Malar J. 2013 Feb 22; 12:74).
Regarding claim 1, 3 and 19-20, Lee teaches a biosensor to detect a target clinical marker in a biological fluid sample of a patient. Specifically, Lee teaches a conductive CNT-biosensor in which a variety of bioreceptors are attached to the conductive CNTs (carbon nanotubes) comprising:
a substrate, a plurality of carbon nanotubes deposited on the substrate, and a plurality of gold nanoparticles deposited on the plurality of carbon nanotubes “a CNT monolayer dotted with gold nanocrystals is immobilized to the substrate surface” ([0033]);
a biomolecule “bioreceptors capable of reacting with target biomaterials” and “receptors having functional groups that bind to or react with the gold nanoparticles of gold nanoparticle-dotted CNTs” ([0033]);
Regarding an ex-situ nature of the biosensor, Lee teaches in Example 2 that the biosensor can be used for detection of DNA hybridization ([0113]-[0125]). Specifically, Lee teaches a process step “to remove the non-specific bindings of the double stranded oligonucleotides, the solution was left at 100°C” ([0121]), clearly, such temperature can only be achieved ex-situ.
Regarding the limitation reciting “a handheld device”, MPEP 2144.04 instructs that the fact that a claimed device is portable or movable is not sufficient by itself to patentably distinguish over an otherwise old device unless there are new or unexpected results (In re Lindberg, 194 F.2d 732, 93 USPQ 23 (CCPA 1952)). Additionally, the biosensor of Lee fits on a glass slide ([0113]), therefore, it is inherently small enough to be handheld.
Regarding the limitations of the gold nanoparticles deposited on the carbon nanotube, Lee teaches “the present invention provides conductive CNTs dotted with a metal” and “metal is preferably gold” ([0046]). The limitation of the gold nanoparticles electrodeposited on the carbon nanotube is directed to the process of gold deposition. MPEP 2113 instructs, that “[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985)”.
In the present case, the final product is the same gold nanoparticles deposited on the carbon nanotubes. Evidence that the gold nanoparticles are functionally the same, comes from Lee’s teaching that the gold nanoparticles do not have to be electrodeposited to be used in the biosensor “various bioreceptors having functional groups that react with the gold nanocrystals present in the high-density CNT pattern are attached to the CNT pattern or film, to fabricate a biosensor that can detect various target biomaterials directly or by electrochemical signals” ([0061]).
Regarding the limitation of a biotinylated antibody or an aptamer, Lee teaches that avidin-biotin can be used for immobilization of the biomolecules on the biosensor “methods can be classified into several categories, including chemical adsorption, covalent-binding, electrostatic attraction, co-polymerization, and avidin-biotin affinity approaches” ([0018]).
Regarding the limitation of a test strip comprising the biosensor, Lee teaches the biosensor assembled on the surface of a glass slide ([0113]). Fig. 3(d) teaches the carbon nanotubes deposited on the substrate occupy only a portion of the glass slide substrate forming the biosensor. The remaining glass slide surface acts as a test strip supporting the biosensor. Therefore, Lee teaches a test strip comprising the biosensor.
Regarding the mechanism to provide an indication of the presence or absence of the target clinical marker in the biological fluid sample of the patient, Lee teaches that the indication mechanism is already built in to the biosensor in the form of conductive carbon nanotubes “various target biomaterials that bind or react with the bioreceptors can be precisely measured directly or by electrochemical signals at large amounts in one step” (Abstract). The conductive carbon nanotubes are the structure/mechanism in the biosensor that provides an indication of the presence or absence of the target.
Lee does not specifically teach biotinylated antibodies attached to the binding material adsorbed on the plurality of gold nanoparticles, a target bone or tissue marker, and a visual chart or key.
Regarding claim 1, Springer teaches “Biofunctionalized gold nanoparticles for SPR-biosensor-based detection of CEA in blood plasma” (Title). Springer also teaches biotinylated antibodies attached to the binding material adsorbed on gold nanoparticles. Specifically, Springer teaches gold nanoparticles (Bio-AuNPs) functionalized with streptavidin to provide high affinity for the biotinylated antibody used in a sandwich assay (Abstract), where streptavidin corresponds to the binding material of the instant disclosure. Streptavidin taught by Springer and avidin taught by Lee are widely known in the art for their exceptionally strong and specific interaction with biotin, and are used interchangeably.
Lee and Springer fail to teach a target bone or tissue marker and a visual chart or key.
Regarding claim 1, Amama teaches “C-Telopeptide and N-Telopeptide: the Predictive Value of Biochemical Markers of Bone Turnover” (Title). Amama also teaches a target clinical bone marker.
Specifically, Amama teaches C-telopeptide as a human bone resorption marker (Abstract, 1st paragraph). The terms C-terminal telopeptide and C-telopeptide are used interchangeably (see Abstract and pg. 334, Col. 1, 2nd paragraph of section “Biochemical markers”). Biotinylating antibody specific for the c-terminal telopeptide meets the limitation of claim 3 reciting biotinylated biomolecule is c-terminal telopeptide antibody.
Additionally, Amama teaches that the c-terminal telopeptide was detected by ELISA using corresponding antibody “obtained by immunizing rabbits with the amino acid sequence specific for a part of the C-terminal telopeptide” (pg. 334, Col. 1, 2nd paragraph of section “Biochemical markers”), where the antibody with the specificity to the c-terminal telopeptide corresponds to the biotinylated biomolecule of the instant disclosure.
Lee, Springer and Amama fail to teach a visual chart or key that correlates the visible color change of the test strip to the presence of the marker in the biological fluid sample of the patient.
Regarding claim 1, Ling teaches visual sandwich immunoassay system (Title). Ling also teaches a chart or key to correlate the visual change to the presence of a marker in the biological sample.
Specifically, Ling teaches plasmon resonance scattering immunoassay with visual detection of a signal “findings showed that the strong PRS signals from the AgNPs immunotargeted on the glass slides can be clearly seen and distinguished by naked eyes under the excitation of a common white light-emitting diode (LED) torch” (Abstract). Additionally, Ling teaches a visual chart with panels A to F showing glass slides bound with different amounts of analyte, that can be used to estimate the quantity of the analyte (Fig. 10).
It would have been obvious to one having ordinary skill in the art at the time the invention was made to have modified the biosensor of Lee, by employing adsorption of biotinylated antibodies on the streptavidin binding material immobilized on the gold surface as taught by Springer, as a simple substitution of one known element for another to obtain predictable results.
One having ordinary skill in the art would have had a reasonable expectation of success in combining the prior art references because immobilization of biomolecules using avidin-biotin taught by Lee ([0018]) and streptavidin-biotin taught by Springer are well-known approaches in the art.
It would have been obvious to one having ordinary skill in the art at the time the invention was made to have modified the biosensor of Lee and Springer, by employing an antibody specific to the c-terminal telopeptide as a bone marker as taught by Amama, as an obvious matter of combining prior art elements according to known methods to yield predictable results. Lee is generic with respect to the type of receptor that can be incorporated and the antibody specific for the c-terminal telopeptide as taught by Amama (pg. 334, Col. 1, 2nd paragraph of section “Biochemical markers”) provides a method for monitoring bone turnover (Abstract).
Each prior art element would have been expected to independently contribute its own known properties to the final biosensor and the results would have been reasonably predictable.
It would have been obvious to one having ordinary skill in the art at the time the invention was made to have modified the biosensor of Lee, Springer, and Amama, by employing a visual chart as taught by Ling, in order to provide a signal quantitation aid (visual chart) for a simple and inexpensive biosensor. One having ordinary skill in the art would have been motivated to make such a change, because the visual chart replaces expensive, dedicated readers and makes detection of clinical markers very affordable “Figure 10 exhibits the photographs of six pieces of glass slides directly captured with a common digital camera under proper illumination of a white LED torch” (Ling, pg. 1713, Col. 2, last paragraph).
One having ordinary skill in the art would have had a reasonable expectation of success in combining the prior art references because the prior art of Ling is relying on light-scattering labels commonly used in “plasmon resonance scattering signals from silver nanoparticles (AgNPs) immunotargeted on glass slides” (Abstract). Biosensors of Ling, Lee, Springer and Amama are similarly drawn to immunoassays.
Lee, Springer, Amama, and Ling fail to teach a test strip with a visible color change of the test strip when contacted with the biological fluid sample of the patient.
Regarding claim 1, Ongagna-Yhombi teaches analysis of a PCR amplicon yield using lateral flow detection with a quantitative up-converting phosphor reporter technology (Abstract. Conclusions). Ongagna-Yhombi also teaches a test strip biosensor with a visible change displayed on the test strip.
Specifically, Ongagna-Yhombi teaches a rapid, non-invasive, and inexpensive point-of-care diagnostic for malaria (Abstract. Background) with a lateral flow test strip (Fig. 2A). The target clinical marker (PCR product of a P. falciparum-specific DNA sequence) is captured on the lateral flow test strip using avidin, and detection is performed using up-converting phosphors label (pg. 2, col. 2, last par., and Fig. 1). The capture is achieved via biotinylated PCR primer U2 (pg. 3, col. 1, par. 1). The up-converting phosphors label attached to the PCR product is detected visually at 455 nm, meeting the limitation of claim 1 reciting visible color change of the test strip when contacted with the biological fluid sample of the patient and claim 19 reciting the visible color change of the test strip corresponds with a color and/or the intensity of a color on the visual chart or key to determine a level of the target.
Additionally, Ongagna-Yhombi teaches sandwich format of analyte detection, wherein the up-converting phosphors label binds to the test strip only when the analyte is present (Fig.2A) – the analyte acts as a bridge between avidin bound to the test line and the label. Therefore, no visible color change of the test strip when contacted with the biological fluid sample of the patient indicates an absence of the target marker in the biological fluid sample of the patient, meeting claim 20. This is an inherent property of the sandwich assay format.
It would have been obvious to one having ordinary skill in the art at the time the invention was made to have modified the biosensor of Lee, Springer, Amama, and Ling, by employing a test strip assay as taught by Ongagna-Yhombi, in order to design a biosensor with a visible color change of the test strip because the combination of the test strip format with a simple, visual detection of the assay results provides rapid and inexpensive point-of-care assays. One having ordinary skill in the art would have been motivated to make such a change to be able to detect target clinical bone or tissue markers in a patient sample at the time of the patient visit. The use of such an assay would have been desirable to those of ordinary skill in the art because faster diagnostics leads to better healthcare.
One having ordinary skill in the art would have had a reasonable expectation of success in combining the prior art references because both assays of Lee, Springer, Amama, and Ling, and Ongagna-Yhombi are similarly drawn to biotin-avidin capture of the analyte and visual detection of the results: blue light scattering (Lee, Springer, Amama, Ling) and 455 nm emission light (Ongagna-Yhombi). The glass slide of Lee and the strip of Ongagna-Yhombi play support role for the capture components of the assays and do not affect visual detection of the analyte.
Regarding claim 5, Lee teaches that avidin-biotin can be used for immobilization of the biomolecules on the biosensor ([0018]). Avidin meets the limitation of claim 5 reciting the binding material is avidin.
Response to Arguments
Applicant’s arguments filed June 15, 2026 have been fully considered.
Claims 1, 3, 5 and 19-20 were rejected under 35 U.S.C. 103.
Applicant argues that “Lee does not teach or suggest a visible color change of the glass slide surface ("test strip") being indicative of biotinylated antibodies attached to the binding material, as required in claim 1 of the present invention” (pg. 7, par. 3).
The argument is not persuasive because Applicant is arguing against references individually. In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Lee is not cited of its teachings of a visible color change of the glass slide surface. Lee is cited of its teachings of a conductive CNT-biosensor in which a variety of bioreceptors are attached to the conductive CNTs (carbon nanotubes) comprising:
a substrate, a plurality of carbon nanotubes deposited on the substrate, and a plurality of gold nanoparticles deposited on the plurality of carbon nanotubes “a CNT monolayer dotted with gold nanocrystals is immobilized to the substrate surface” ([0033]);
a biomolecule “bioreceptors capable of reacting with target biomaterials” and “receptors having functional groups that bind to or react with the gold nanoparticles of gold nanoparticle-dotted CNTs” ([0033]).
It is Ling who teaches a chart or key to correlate the visual change to the presence of a marker in the biological sample. Specifically, Ling teaches plasmon resonance scattering immunoassay with visual detection of a signal “findings showed that the strong PRS signals from the AgNPs immunotargeted on the glass slides can be clearly seen and distinguished by naked eyes under the excitation of a common white light-emitting diode (LED) torch” (Abstract). Additionally, Ling teaches a visual chart with panels A to F showing glass slides bound with different amounts of analyte, that can be used to estimate the quantity of the analyte (Fig. 10).
Applicant argues that “there is no teaching or suggestion in Springer and Amama that overcomes or cures the shortcomings and deficiencies of Lee” (pg. 7, par. 4). The argument is not persuasive because Applicant fails to indicate which specific shortcomings and deficiencies of Lee Springer and Amama fail to cure or overcome.
As presented in the OA (29 December 2025) Lee does not specifically teach biotinylated antibodies attached to the binding material adsorbed on the plurality of gold nanoparticles, and a target bone or tissue marker.
Springer teaches “Biofunctionalized gold nanoparticles for SPR-biosensor-based detection of CEA in blood plasma” (Title). Springer also teaches biotinylated antibodies attached to the binding material adsorbed on gold nanoparticles. Specifically, Springer teaches gold nanoparticles (Bio-AuNPs) functionalized with streptavidin to provide high affinity for the biotinylated antibody used in a sandwich assay (Abstract), where streptavidin corresponds to the binding material of the instant disclosure. Streptavidin taught by Springer and avidin taught by Lee are widely known in the art for their exceptionally strong and specific interaction with biotin, and are used interchangeably.
Lee and Springer fail to teach a target bone or tissue marker.
Amama teaches “C-Telopeptide and N-Telopeptide: the Predictive Value of Biochemical Markers of Bone Turnover” (Title). Amama also teaches a target clinical bone marker.
Specifically, Amama teaches C-telopeptide as a human bone resorption marker (Abstract, 1st paragraph). The terms C-terminal telopeptide and C-telopeptide are used interchangeably (see Abstract and pg. 334, Col. 1, 2nd paragraph of section “Biochemical markers”). Biotinylating antibody specific for the c-terminal telopeptide meets the limitation of claim 3 reciting biotinylated biomolecule is c-terminal telopeptide antibody.
Additionally, Amama teaches that the c-terminal telopeptide was detected by ELISA using corresponding antibody “obtained by immunizing rabbits with the amino acid sequence specific for a part of the C-terminal telopeptide” (pg. 334, Col. 1, 2nd paragraph of section “Biochemical markers”), where the antibody with the specificity to the c-terminal telopeptide corresponds to the biotinylated biomolecule of the instant disclosure (OA, pg. 5, par. 4 – pg. 6, par. 2).
As such, Springer and Amama do teach the missing limitations reciting biotinylated antibodies attached to the binding material adsorbed on the plurality of gold nanoparticles, and a target bone or tissue marker.
Applicant argues that “With respect to Ling, the Applicant respectfully submits that this reference does not teach in any context a test strip comprising a biosensor wherein there is a visible color change of the test strip when it is contacted with a patient's biological fluid sample in which the target clinical bone or tissue marker is present. Hence, additionally, Ling does not mention a visual chart or key that correlates a visible color change of a test strip to the presence of the target clinical bone or tissue marker in the biological fluid sample” (pg. 8, par. 2).
The argument is not persuasive because Applicant is arguing against references individually. In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Ling is not cited of its teachings of the target clinical bone or tissue marker. Ling is cited of its teachings of a visible color change of the glass slide surface. Amama is cited of its teachings of the target clinical bone or tissue marker: C-telopeptide as a human bone resorption marker (Abstract, 1st paragraph). The terms C-terminal telopeptide and C-telopeptide are used interchangeably (see Abstract and pg. 334, Col. 1, 2nd paragraph of section “Biochemical markers”). Biotinylating antibody specific for the c-terminal telopeptide meets the limitation of claim 3 reciting biotinylated biomolecule is c-terminal telopeptide antibody (OA, pg. 5, last par.). Ongagna-Yhombi teaches visible color change of a test strip to the presence of the target: a rapid, non-invasive, and inexpensive point-of-care diagnostic for malaria (Abstract. Background) with a lateral flow test strip (Fig. 2A). The target clinical marker (PCR product of a P. falciparum-specific DNA sequence) is captured on the lateral flow test strip using avidin, and detection is performed using up-converting phosphors label (pg. 2, col. 2, last par., and Fig. 1). The capture is achieved via biotinylated PCR primer U2 (pg. 3, col. 1, par. 1).
Applicant argues that “contrary to the presently claimed invention, Ling does not mention (i) a visible color change of the test strip ("glass slide") when contacted with a patient's biological fluid sample, (ii) wherein a target clinical bone or tissue marker is present, or (iii) a visual chart or key that correlates a visible color change of the test strip to the presence of the target clinical bone or tissue marker in the biological fluid sample. That is, the change described in Ling is visibly displayed or deposited on the glass slide because of the AgNPs immunotargeted thereon, but the color of the glass slide does not change. Thus, the color of the glass slide would not be correlated to the presence or absence of a target marker in a biological fluid sample as required by claim 1 of the present invention” (pg. 8, par. 3).
The argument is not persuasive because Applicant is arguing against references individually. In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Ling is not cited of its teachings of the target clinical bone or tissue marker. Amama is cited of its teachings of the target clinical bone or tissue marker. Ling is cited of its teachings of a chart or key to correlate the visual change to the presence of a marker in the biological sample. Ling teaches plasmon resonance scattering immunoassay with visual detection of a signal “findings showed that the strong PRS signals from the AgNPs immunotargeted on the glass slides can be clearly seen and distinguished by naked eyes under the excitation of a common white light-emitting diode (LED) torch” (Abstract). Additionally, Ling teaches a visual chart with panels A to F showing glass slides bound with different amounts of analyte, that can be used to estimate the quantity of the analyte (Fig. 10) (OA, pg. 6, par. 5). Ongagna-Yhombi teaches visible color change of a test strip to the presence or absence of the target: a rapid, non-invasive, and inexpensive point-of-care diagnostic for malaria (Abstract. Background) with a lateral flow test strip (Fig. 2A). The target clinical marker (PCR product of a P. falciparum-specific DNA sequence) is captured on the lateral flow test strip using avidin, and detection is performed using up-converting phosphors label (pg. 2, col. 2, last par., and Fig. 1). The capture is achieved via biotinylated PCR primer U2 (pg. 3, col. 1, par. 1).
Additionally, the argument is confusing because Applicant wants the glass slide to change the color, while Ling teaches that AgNPs deposited on the glass slide change the color. Applicant is reminded that the specification fails to support the color change of the glass slide or the test strip material per se. It is the visual label deposited on the test strip that is contributing to the color change.
Applicant argues with Ongagna-Yhombi’s teaching of a test strip biosensor with a visible change displayed on the test strip (pg. 8, last par. - pg. 9, par. 2). Specifically, Applicant states that “O-Y discloses a "single" visible color at 455 nm (blue) and a change in the "intensity" of the phosphorescent of that "single" color in Lanes 1 through 6. Furthermore, for Lanes 7-13 there appears to be no noticeable change in "intensity" as displayed” (pg. 9, par. 2).
The argument is not persuasive because Lanes 7-13 do not show noticeable change in intensity due to the amount of the analyte being below the detection limit of the assay. Lanes 1 through 6 have sufficient amounts of the analyte and do show change in intensity supporting Ongagna-Yhombi teaching of a test strip biosensor with a visible change displayed on the test strip.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Alexander Volkov whose telephone number is (571) 272-1899. The examiner can normally be reached M-F 9:00AM-5:00PM (EST).
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Bao-Thuy Nguyen can be reached on (571) 272-0824. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ALEXANDER ALEXANDROVIC VOLKOV/
Examiner, Art Unit 1677
/REBECCA M GIERE/Primary Examiner, Art Unit 1677
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