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 .
Claim Objections
Claims 9, 12, 13, and 15 are objected to because of the following informalities:
a) in claim 9, line 4, “tert-butyl,” should be replaced with –tert-butyl; --[semi-colon];
b) in claim 9, lines 5-6, the phrase “form together” should only occur once in “or R2 and R3 form together form together [underlining by the Examiner]”;
c) in claim 9, line 7, “heteroatom, X” should be replaced with – heteroatom; and
X --;
d) in claim 12, line 3, “and a counter electrode.” should be – or a counter electrode. – (the electrode cannot be a working electrode, a reference electrode, and a counter electrode all at once);
e) in claim 13, step (c), “(c) adding a third solution comprising a cross-linking agent on the electrode surface obtained at the end of step (b); . . . .” should be
-- “(c) adding a third solution comprising a cross-linking agent to the electrode surface obtained at the end of step (b); . . . . --; and
f) in claim 15, line 5, “. . . ., and a counter electrode.” should be – . . . ., or a counter electrode. – (the electrode cannot be a working electrode, a reference electrode, and a counter electrode all at once).
Appropriate correction is required.
Claim Rejections - 35 USC § 112
Note that dependent claims will have the deficiencies of base and intervening claims.
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 8-10 and 12-15 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:
a) claim 8 requires “. . . . wherein n is an integer comprised between 1 and 2.” This phase is indefinite as there is no integer between 1 and 2. Does Applicant mean -- wherein n is an integer equal to 1 or 2 -- ?
b) regarding claim 9, the phrase "preferably" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
c) claim 9 requires “. . . . wherein n is an integer between 2 and 3.” This phase is indefinite as there is no integer between 2 and 3. Does Applicant mean -- wherein n is an integer equal to 2 or 3 -- ?
d) claim 10 requires “. . . ., further comprising on the respective surface at least one neutralizing agent.” Claim 14 requires “. . . ., wherein a fifth solution comprising a neutralizing agent is added to the surface of the electrode obtained at the end of step (d).” The scope of the term “neutralizing agent” is indefinite. Does it include acids, bases, and buffer compounds? If Applicant is being his own lexicographer, please heed MPEP 2173.05(a).
e) claim 12 requires the limitation “comprising an electrode according to claim 1, as a working electrode, a reference electrode and a counter-electrode.” The Examiner requests Applicant to clarify whether he is using “a reference electrode” and “a counter-electrode” here in an unconventional manner as it seems that having analyte bind to the magnetic nanoparticles on a reference electrode or a counter electrode would effectively make the “reference electrode” or “a counter-electrode” into a working electrode as conventionally understood. Put another way, how can, for example, the reference electrode maintain a stable reference potential if it is configured to have a reactive electrode surface?
f) claim 13 recites the limitation "(a) adding gold- or silver-coated magnetic nanoparticles to a first solution comprising at least one compound of formula (I) as defined above, . . . ." in lines 4-5. There is insufficient antecedent basis for this limitation in the claim. There is no formula (I) earlier in claim 13 or in claim 1, from which claim 13 depends.
g) claim 13 requires
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Applicant is requested to clarify the scope of the word “solution” in second solution as it is not clear how an adsorbed compound can be said to be in solution. If Applicant is being his own lexicographer, please heed MPEP 2173.05(a).
f) claim 15 requires the limitation “comprising an electrode according to claim 1, as a working electrode, a reference electrode and a counter-electrode, . . . .” The Examiner requests Applicant to clarify whether he is using “a reference electrode” and “a counter-electrode” here in an unconventional manner as it seems that having analyte bind to the magnetic nanoparticles on a reference electrode or a counter electrode would effectively make the “reference electrode” or “a counter-electrode” into a working electrode as conventionally understood. Put another way, how can, for example, the reference electrode maintain a stable reference potential if it is configured to have a reactive electrode surface?
f) claim 15, lines 4-5 requires the limitation “comprising an electrode according to claim 1, as a working electrode, a reference electrode and a counter-electrode, . . . .” However, lines 6-8, requires “. . . ., under conditions such that the analyte binds to an analyte-specific ligand present on the working electrode and the binding of the analyte to the ligand results in a change in current flow between the working electrode and the counter- electrode; and . . . .” These limitations are not consistent.
g) claim 15, step (b), requires “(b) detecting the change in current generated in step (a) by determining the presence or amount of the analyte in the sample.” Should this step not be reversed, that is, -- (b) determining the presence or amount of the analyte in the sample by detecting the change in current generated in step (a) --?
Allowable Subject Matter
Claim 1-7 and 11 are allowed.
Claims 8-10 and 12-15 would be allowable if rewritten to overcome the rejections under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), 2nd paragraph, set forth in this Office action and to include all of the limitations of the base claim and any intervening claims.
The following is an examiner’s statement of reasons for allowance:
a) in claim 1 the combination of limitations requires the following underlined features
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a)(i) the International Search Report for international application no. PCT/IB2022/061784 cites an article by Pham et al. as a “Y” document against claims 1-15 of that application, an article by Silva et al. as a “Y” document against claims 6-9, an article by Rawal et al. as a “Y” document against claims 6-9, US 9581590 B2 as a “Y” document against claims 1-10 and 12-15, and an article by Yang et al. as a “Y” document against claims 1-5, 11-13, and 15. The Written Opinion for international application no. PCT/IB2022/061784 deems claims 1-15 to have novelty, but lack an inventive step over the aforementioned “Y” documents, which are referred to respectively as documents D1-D5.
Regarding D1, in contrast to claim 1 of U.S. application 18/717147, there is nothing to suggest that the sensing electrode in D1 meets the claim 1 limitation “comprising on the respective surface at least one free amine or carboxyl group” [italicizing by the Examiner] or that this feature is desirable. In the Pham article section entitled “Preparation of nanoparticles---protein conjugates for measuring fluorescence”, which is on Pham page 229, the following is stated,
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One of ordinary skill in the art would understand from this passage that an excess of IgG relative to the EDC/NHS is provided and/or it is desired to make use of all of the EDC/NHS by binding IgG to them as extensively as possible.
Additionally, regarding D1, it does not appear that the U.S. application claim 1 limitation “the nanoparticles being adsorbed on the surface of the electrode, . . .[italicizing by the Examiner]” is met as D1 states under “Preparation of electrode”, which is on page 229,
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Regarding D2, it does not cure the deficiencies of D1 noted above. In fact, D2 teaches away from the U.S. application claim 1 limitation “the nanoparticles being adsorbed on the surface of the electrode, . . .” See in D2 especially Figures 6 and 7, 4.1.1. Au@MNPs based electrochemical biosensors with a fixed .position sensing interface., which discloses holding the nanoparticles onto the electrode surface by magnetic force; 4.1.2. Au@MNPs as dispersible nanoelectrodes., which discloses “Here, Au@MNPs are dispersed into a solution where they bind to a desired analyte before a magnetic field is applied to direct the nanoparticles to a conducting surface to detect the analyte (Fig. 6)…[italicizing by the Exam9iner]”; and 4.1.3. Biochemiresistor. Which discloses, “ Using the Au@MNP sensing system, Gooding and co-workers86 described . a new class of biosensor, referred to as biochemiresistor, which is made possible by the ability to magnetically assemble the nanoparticles, when desired, as a film across two electrodes. [italicizing by the Examiner]”
Regarding D3, it does not cure the deficiencies of D1 noted above. In fact, D3 teaches away from the U.S. application claim 1 limitation “the nanoparticles being adsorbed on the surface of the electrode, . . .” See in D3 the Abstract and 2. 7. Electrodeposition of Fe304 @GNPs onto Au electrode, which discloses that the nanoparticles are electrodeposited on the surface of the electrode.
Regarding D4, it does not cure the deficiencies of D1 noted above. In fact, D4 teaches away from the U.S. application claim 1 limitation “the nanoparticles being adsorbed on the surface of the electrode, . . .” D4 discloses
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See D4 col. 33:58-67.
Also see D4 Figure 15.
Regarding D5, it does not cure the deficiencies of D1 noted above. In fact, D5 teaches away from the U.S. application claim 1 limitation “the nanoparticles being adsorbed on the surface of the electrode, . . .” D5 discloses
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Although the D5 Abstract does contain the sentence “ HRP were adsorbed on the surface with the aid of an external magnetic field to fabricate the
SPCEiGS- Nafion /Fe1 0 4 -Au-HRP electrode. [italicizing by the Examiner]”, this is an unconventional use of the word “adsorb” (magnetic retention) in the art not intended by Applicant: “[0029] The fact that the nanoparticles are adsorbed on the electrode surface also offers advantages in determining the analyte. In fact, in this way, it is not necessary to use the magnet during the measurement.” See paragraph [0029] of Applicant’s pre-grant application publication
US 20250044251 (”Applicant’s PG-PUB”). Moreover, D5 does not disclose, as required by U.S. application claim 1, “. . . , and (ii) at least one ligand capable of specifically binding to the analyte, the at least one ligand being conjugated to the nanoparticles.” The nanoparticles in D5 are coated with horseradish peroxidase, unlike in D1 in which the nanoparticles are coated with human IgG. So, also, even if the nanoparticles in D5 can somehow be said to adsorb onto the electrode surface this cannot be extrapolated to human IgG in D1.
a)(ii) Zhang et al. Chin J Anal Chem, 2013, 41(9), 1353–1358 (hereafter “Zhang”) discloses an electrode for electrochemical detection of an analyte in a biological sample (see the title), wherein the electrode is a printed, miniaturized, carbon-based electrode (see the title, 2.3.1 Preparation of SPE, and Figure 1) and comprises (i) magnetic nanoparticles coated with gold (see the title and Abstract), and (ii) at least one ligand (the antibody of microcystin-(leucine-arginine) (anti-MCLR)) capable of specifically binding to the analyte, the at least one ligand being conjugated to the nanoparticles (see the title and 2.3.2 Modification of electrode). However, it cannot be determined whether or not the nanoparticles comprise, as required by U.S. application claim 1 “on the respective surface at least one free amine or carboxyl group, . . . .” as Zhang or states in this regard, “A 10-µL aliquot of 1.0 g L–1 Fe3O4@Au NPs suspension was modified onto the surface of working electrode of the SPE which was fixed onto magnet and anti-MCLR of 10 µL (1.0 mg L–1) was immobilized on the film surface of Fe3O4@Au NPs.[italicizing by the Examiner]” See 2.3.2 Modification of electrode. Also, Zhang does not disclose “the nanoparticles being adsorbed on the surface of the electrode, . . . .”; the nanoparticles are held by magnetic force on the surface of the electrode. See 2.3.2 Modification of electrode and
Figure 2.
a)(iiI) Loyprasert et al., “Label-free capacitive immunosensor for microcystin-LR using self-assembled thiourea monolayer incorporated with Ag nanoparticles on gold electrode,” Biosensors and Bioelectronics 24 (2008) 78–86 (hereafter “Loyprasert”) discloses an electrode for electrochemical detection of an analyte in a biological sample (see the title), wherein the electrode comprises (i) nanoparticles made of silver (see the title, Abstract, and Figure 1(b) (first step, “Colloidal Ag”), the nanoparticles being adsorbed on the surface of the electrode (Figure 1(b) (first step, “Colloidal Ag”) and the third paragraph of 2.3. Immobilization of anti-MCLR ), and (ii) at least one ligand (Anti-MCLR; see the Abstract) capable of specifically binding to the analyte (see Figure 1(b), third step (“MCLR”)), the at least one ligand being conjugated to the nanoparticles (Figure 1(b), second step (“Anti-MCLR”), and the third paragraph of 2.3. Immobilization of anti-MCLR).
In contrast to U.S. application claim 1 though, Loyprasert does not meet the limitation “. . . , wherein the electrode is a printed, miniaturized, carbon-based electrode . . . .”. The electrode in Loyprasert, although miniaturized is a gold disc. See the first paragraph of 2.3. Immobilization of anti-MCLR and Figure 1(b). Also, the nanoparticles are not magnetic nor do they appear to comprise “ on the respective surface at least one free amine or carboxyl group.”
b) claims 2-15 depend directly or indirectly from allowable claim 1.
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/ALEXANDER S NOGUEROLA/ Primary Examiner, Art Unit 1795