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 .
Priority
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 3/23/2023 and 6/20/2024 have been considered by the examiner.
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-11 and 17, in the reply filed on 5/2/2025 is acknowledged.
Claim Objections
Claim 3 is objected to because of the following informalities:
In claim 3 line 3, “an silver/gold alloy” should be amended to --[[an]] a silver/gold alloy--.
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.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-11 and 17 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 recites the limitation "the oxidation potential" in line 17. There is insufficient antecedent basis for this limitation in the claim. Claims 2-11 are further rejected by virtue of their dependence upon and because they fail to cure the deficiencies of indefinite claim 1.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 3 recites the broad recitation “the label comprises […] a metal nanoparticle of silver or alloys thereof […] or a metal nanoparticle comprising […] a silver/gold alloy,” and the claim also recites “the label […] consists of a metal nanoparticle of silver or alloys thereof; specifically a silver nanoparticle, or a metal nanoparticle […] consisting of a silver/gold alloy; more specifically a citrate-capped or citrate-stabilized silver nanoparticle” (emphasis added) which are the narrower statements of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims. Claim 4 is further rejected by virtue of its dependence upon and because it fails to cure the deficiencies of indefinite claim 3.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 5 recites the broad recitation “the at least one binding agent is immobilized on the surface of the electrode,” and the claim also recites “preferably via a linker” which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 6 recites the broad recitation “wherein the at least one binding agent and/or the at least one further binding agent are selected from antibodies and fragments thereof, nucleic acids, aptamers, peptide nucleic acids (PNAs), receptor or ligand proteins or peptides, and enzymes,” and the claim also recites “preferably the binding agent and/or the further binding agent comprises an antibody, more preferably an IgG” which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 8 recites the broad recitation “the electrochemical detection in step (v) comprises pulse voltammetry measurements,” and the claim also recites “in particular differential pulse voltammetry (DPV) measurement” which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 10 recites the broad recitation “the analyte is a protein, a carbohydrate, a polynucleotide or a lipid,” and the claim also recites “preferably a protein, more preferably a protein present in a body fluid” which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Regarding claim 17, the use of a sensing device merely recites a use without any active, positive steps delimiting how this use is actually practiced. Therefore, the scope of claim 17 is indefinite (see MPEP 2173.05 [q]).
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claim 17 is rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter. The claim does not fall within at least one of the four categories of patent eligible subject matter because "use" claims that do not purport to claim a process, machine, manufacture, or composition of matter fail to comply with 35 U.S.C. 101 and furthermore, the use claim of claim 17 fails to set forth any steps (MPEP 2173.05 [q]).
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-6, 8-10, and 17 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Miyuki et al. (JP 2009025217 A, referencing furnished machine translation). Pollok et al. (“Electrochemical Detection of NT-proBNP Using a Metalloimmunoassay on a Paper Electrode Platform,” 2020, ACS Sensors, vol. 5, pgs. 853-860) is applied as evidence for claims 1 and 17, and Heidegger et al. (“Human Chorionic Gonadotropin (hCG)—An Endocrine, Regulator of Gestation and Cancer,” 2018, Int. J. Mol. Sci., vol. 19(5), pgs. 1-3) is applied as evidence for claim 10.
Regarding claim 1, Miyuki teaches a method for detecting at least one analyte by electrochemical detection (a method for measuring a test substance [0001]), comprising:
(i) contacting a fluid sample suspected to comprise the at least one analyte (test substance 3 in Fig. 1a) with the surface of an electrode (working electrode 1 in Fig. 1a) comprising at least one binding agent (primary antibody 2 in Fig. 1a) capable of binding to the analyte (solution containing an unknown amount of test substance 3 is supplied to the surface of the working electrode 1 functionalized with primary antibody 2 in Fig. 1a [0021]);
(ii) contacting the fluid sample suspected to comprise the at least one analyte with at least one detection agent (a solution containing secondary antibody 4 labeled with silver nanoparticle 5 is applied to working electrode 1 in Fig. 1a [0020]), wherein the at least one detection agent comprises at least a further binding agent capable of binding to the analyte (secondary antibody 4 in Fig. 1a) and a label (silver nanoparticle 5 in Fig. 1a), wherein the label comprises a metal nanoparticle (silver nanoparticle 5) with a standard redox potential E⁰ between 0 V and 1.2 V (as evidenced by Pollok, the standard redox potential of silver is 0.79 V [pg. 854, col. 2, para. 1], which falls within the claimed range);
(iii) forming a detection complex on the surface of the electrode comprising at least the at least one binding agent, the at least one detection agent and the analyte (after the solutions are applied to working electrode 1, a complex is formed including the primary antibody 2, test substance 3, and secondary antibody 4, and silver nanoparticle 5 in Fig. 1a [0021]);
(iv) precipitating at least a part of the label onto the electrode surface (silver from oxidized silver nanoparticles 5 is deposited on the surface of the working electrode 1 in Fig. 1c [0023]); and
(v) detecting the at least one analyte by electrochemical detection (the silver deposited on working electrode 1 is reoxidized and the oxidation current is measured using differential pulse voltammetry, which is then correlated to the concentration of test substance 3 in Fig. 1d [0017, 0024]);
wherein the method comprises a step of dissolving at least a part of the label by oxidation prior to precipitating at least a part of the label in step (iv) (silver nanoparticles 5 are oxidized to form silver ions in Fig. 1b prior to the silver precipitation step in Fig. 1c [0022-0023]), and
wherein the step of dissolving at least a part of the label by oxidation comprises applying a voltage at the electrode suitable to oxidize the metal nanoparticle (silver nanoparticles are electrochemically oxidized by applying a potential between 1.0-1.5 V to the working electrode [0014, 0022]), wherein a positive potential higher than the oxidation potential of the respective metal nanoparticle is applied as this voltage (the applied potential is higher than the oxidation potential of the silver nanoparticles to induce oxidation into dissolved silver ions in Fig. 1b [0014, 0022]).
The limitation “wherein the applied voltage results in direct oxidation of the metal nanoparticle” is an intended result of the positively recited step of “applying a voltage at the electrode.” The court noted that a "‘whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.’" Id. (quoting Minton v. Nat’l Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003)).
Regarding claim 2, Miyuki teaches the method according to claim 1, and further teaches the method comprising: a step of forming an analyte complex on the surface of the electrode comprising the at least one binding agent and the analyte, prior or simultaneously to step (iii) of forming of the detection complex (the solution containing test analyte 3 and the solution containing secondary antibody 4 labeled with silver nanoparticle 5 can be applied separately or simultaneously to working electrode 1 in Fig. 1a, such that an analyte complex of test analyte 3 bound to primary antibody 2 is formed either prior to or simultaneously with the formation of the detection complex [0021]).
Regarding claim 3, Miyuki teaches the method according to claim 1, and further teaches wherein the label comprises or consists of a metal nanoparticle of silver or alloys thereof; specifically a silver nanoparticle (nanoparticles 5 in Fig. 1a are silver nanoparticles [0014]).
Regarding claim 4, Miyuki teaches the method of claim 3, and further teaches wherein the positive potential is applied as a voltage in the range of 1.0 to 1.5 V (silver nanoparticles are electrochemically oxidized by applying a positive potential between 1.0-1.5 V to the working electrode [0014, 0022], which falls within the claimed range).
Regarding claim 5, Miyuki teaches the method according to claim 1, and further teaches wherein the at least one binding agent is immobilized on the surface of the electrode exposable to the fluid sample (primary antibody 2 is immobilized on the surface of working electrode 1 that is exposed to the solution with test analyte 3 in Fig. 1a [0020-0021]).
Regarding claim 6, Miyuki teaches the method according to claim 1, and further teaches wherein the at least one binding agent and the at least one further binding agent comprise antibodies (as stated in the rejection of claim 1 above, the binding agent and further binding agent are antibodies).
Regarding claim 8, Miyuki teaches the method according to claim 1, and further teaches wherein the electrochemical detection in step (v) comprises differential pulse voltammetry (DPV) measurement (differential pulse voltammetry is used to measure current during the detection step [0017, 0048]).
Regarding claim 9, Miyuki teaches the method according to claim 1, and further teaches wherein the method comprises applying a negative potential following precipitating in step (iv) (the differential pulse voltammetry performed during step (v) includes applying a potential of -0.4 V to 0.4 V to the working electrode, such that a negative potential is applied [0017, 0048]).
Regarding claim 10, Miyuki teaches the method according to claim 1, and further teaches wherein the analyte is a protein (human gonadotropin [hCG] is used as the test substance [0043]. As evidenced by Heidegger, hCG is a glycoprotein [pg. 1, para. 1]).
Regarding claim 17, Miyuki teaches a use of a metal nanoparticle (silver nanoparticle 5 in Fig. 1a) with a standard redox potential E⁰ between 0 V and 1.2 V (as evidenced by Pollok, the standard redox potential of silver is 0.79 V [pg. 854, col. 2, para. 1], which falls within the claimed range) as a label in electrochemical detection of an analyte by pulse voltammetry measurement (silver nanoparticle 5 in Fig. 1a are used to label secondary antibody 4 to electrochemically detect test substance 3 using differential pulse voltammetry [0017, 0020, 0048]).
Claims 1 and 11 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ting et al. (“A DNA biosensor based on the detection of doxorubicin-conjugated Ag nanoparticle labels using solid-state voltammetry,” 2009, Biosensors and Bioelectronics, vol. 25, pgs. 282-287). Pollok is applied as evidence for claim 1.
Regarding claim 1, Ting teaches a method for detecting at least one analyte by electrochemical detection (an electrochemical biosensor for detecting a short DNA oligonucleotide [pg. 282, Abstract]), comprising:
(i) contacting a fluid sample suspected to comprise the at least one analyte (complementary DNA in Fig. 1 is the analyte) with the surface of an electrode (gold electrode in Fig. 1) comprising at least one binding agent (thiol-modified DNA probe in Fig. 1) capable of binding to the analyte (the thiol-modified DNA probe hybridizes with the complementary DNA to form double-stranded DNA in Fig. 1 [pg. 284, col. 1, para. 3; pg. 284, col. 2, para. 1]);
(ii) contacting the fluid sample suspected to comprise the at least one analyte with at least one detection agent (doxorubicin-conjugated Ag nanoparticles in Fig. 1), wherein the at least one detection agent comprises at least a further binding agent capable of binding to the analyte (doxorubicin intercalates in the double-stranded DNA in Fig. 1 [pg. 283, col. 1, para. 3; pg. 284, col. 2, para. 1]) and a label (Ag nanoparticle [pg. 283, col. 1, para. 3]), wherein the label comprises a metal nanoparticle with a standard redox potential E between 0 V and 1.2 V (as evidenced by Pollok, the standard redox potential of silver is 0.79 V [pg. 854, col. 2, para. 1], which falls within the claimed range);
(iii) forming a detection complex on the surface of the electrode comprising at least the at least one binding agent, the at least one detection agent and the analyte (a detection complex of the DNA probe, complementary DNA, and Ag nanoparticle is formed on the surface of the gold electrode in Fig. 1 [pg. 284, col. 2, para. 1]);
(iv) precipitating at least a part of the label onto the electrode surface (the Ag nanoparticles are oxidized into Ag+ and then react with AgCl to form a solid precipitate on the surface of the electrode in Eqs. (1) and (2) [pg. 284, col. 2, para. 2]); and
(v) detecting the at least one analyte by electrochemical detection (the concentration of target DNA is quantified based on the peak current of a reverse cathodic potential scan [pg. 284, col. 2, paras. 2-3; pg. 285, col. 1, para. 1]);
wherein the method comprises a step of dissolving at least a part of the label by oxidation prior to precipitating at least a part of the label in step (iv) (the Ag nanoparticles are dissolved via oxidation prior to precipitation into AgCl [pg. 284, col. 2, para. 2]), and
wherein the step of dissolving at least a part of the label by oxidation comprises applying a voltage at the electrode suitable to oxidize the metal nanoparticle (an anodic potential sweep between -0.2 V to 0.8 V is applied to the electrode to induce oxidation of the Ag nanoparticles in Fig. 3 [pg. 284, col. 2, para. 2]), wherein a positive potential higher than the oxidation potential of the respective metal nanoparticle is applied as this voltage (the applied potential includes a positive value of 0.8 V [see Fig. 3], which is higher than the standard redox potential of Ag).
The limitation “wherein the applied voltage results in direct oxidation of the metal nanoparticle” is an intended result of the positively recited step of “applying a voltage at the electrode.” The court noted that a "‘whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.’" Id. (quoting Minton v. Nat’l Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003)).
Regarding claim 11, Ting teaches the method according to claim 1, and further teaches wherein the precipitating in step (iv) comprises contacting a counter ion with the dissolved part of the label (Cl- is contacted with the electrogenerated Ag+ to form solid AgCl precipitate on the electrode surface in Eq. (1) [pg. 284, col. 2, para. 2]).
The limitation “to allow for forming of an insoluble salt that precipitates from the solution” is an intended result of the positively recited step of “contacting a counter ion with the dissolved part of the label.” The court noted that a "‘whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.’" Id. (quoting Minton v. Nat’l Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003)).
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 7 is rejected under 35 U.S.C. 103 as being unpatentable over Miyuki, as applied to claim 1 above, in view of Hamaly et al. (“Freeze-drying of monoclonal antibody-conjugated gold nanorods: Colloidal stability and biological activity,” 2018, vol. 550, pgs. 269-277).
Regarding claim 7, Miyuki teaches the method according to claim 1, but is silent to the limitation wherein the detection agent is stored in a dry state and solubilized upon the addition of the fluid sample.
Hamaly teaches a method for freeze drying a detection agent (gold nanorods conjugated with a monoclonal antibody in Fig. 1d [pg. 269, Abstract]), wherein the detection agent comprises a binding agent capable of binding to an analyte (monoclonal antibody) and a metal nanoparticle label (gold nanorod), by adding a cryoprotectant to the detection agent suspension and freeze-drying the mixture. Hamaly further teaches that freeze drying the detection agent with a cryoprotectant allows for stable dry storage and shipping while maintaining the biological activity of the detection agent when it is resolubilized [pg. 269, col. 1, para. 1-pg. 269, col. 2, para. 1; pg. 276, col. 2, para. 1].
Miyuki and Hamaly are both considered analogous to the claimed invention because they are in the same field of antibody-conjugated metal nanoparticles. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the detection agent in Miyuki by freeze-drying the detection agent with cryoprotectant and storing in a dry state, as taught in Hamaly, since this would allow for stable storage and shipping while maintaining the biological activity of the detection agent when it is resolubilized [pg. 269, col. 1, para. 1-pg. 269, col. 2, para. 1; pg. 276, col. 2, para. 1 in Hamaly]. With this modification, the detection agent would be solubilized upon addition of the fluid sample (the labeled antibody and solution with the test substance can be supplied simultaneously to the working electrode surface [0021 in Miyuki]). Furthermore, Hamaly teaches the claimed improvement as a known technique that is applicable to the base method in Miyuki. One skilled in the art could have applied the freeze-dried storage of the detection agent in Hamaly in the same way to the base method in Miyuki, yielding predictable results (MPEP 2143(I)(D)).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KAYLEE Y TSENG whose telephone number is (703)756-5542. The examiner can normally be reached Mon - Fri 9-6 PT.
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/K.T./Examiner, Art Unit 1795
/LUAN V VAN/Supervisory Patent Examiner, Art Unit 1795