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
The requirement for species election dated 03/30/2026 has been withdrawn. Upon reconsideration, the species are found to not impose a search burden.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Based on the filing receipt, the effective filing date of this application is December 31, 2020 which is the filing date of Foreign Application Number REPUBLIC OF KOREA 10-2020-0189197 from which the benefit of priority is claimed.
Information Disclosure Statements
The information disclosure statements (IDS) dated 07/22/2025 and 06/28/2023 have
been considered by the examiner.
Status of Claims
Claims 1-17 are pending and examined herein.
Claim Objections
Claims 1, 8, 10, and 12 are objected to because of the following informalities:
Claim 1 recites, “A method by which biosensor device detects”. The claim should recite, “A method by which a biosensor device detects”.
Claims 8, 10, and 12 recite, “phosphate buffer saline”. The claims should recite, “phosphate buffered saline”. 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.
Claim 16 is 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 16 recites, “the impedance of the antibody and the impedance of the antigen-antibody have the relational expression below:
[AltContent: textbox ([img-media_image1.png])]
(where, Z denotes the impedance, Rs denotes a solution resistance, Rb denotes a resistance between the bead and the electrode, Cb denotes a capacitance between the bead and the electrode, and Cdl denotes a capacitance between the electrodes)”.
However, if an artisan simplified the denominator of the fractional term on the right, the denominator would read (jwCdl)(1+jwRbCb). The (1+jwRb-Cb) term on the denominator cancels the same term in the numerator. The equation then simplifies to Z = RS + 1/(jwCdl). See below.
Z
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=
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1
+
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When the equation is simplified, claim 16 recites a relationship between the impedance of the antibody and the impedance of the antigen-antibody complex as depending only on the resistance of the solution and the capacitance between the electrodes, irrespective of the capacitance and resistance between the bead and the electrode. Considering the limitations of independent claim 1, the impedance must depend on the resistance and capacitance between the bead and the electrode because that is how antigen-antibody binding is measured; the impedance of the antibody and the impedance of the antigen-antibody complex cannot depend only on the resistance of the solution and capacitance between the electrodes. Therefore, the metes and bounds of the claim cannot be ascertained. In its current form, the claim cannot be further examined in terms of applying prior art.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 11 and 13 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 11 recites, “the measurement of the impedance of the antibody using the first frequency and the measurement of the impedance of the antibody using the second frequency are performed simultaneously or separately”.
Claim 13 recites, “the measurement of the impedance of the antigen-antibody using the first frequency and the measurement of the impedance of the antigen-antibody using the second frequency are performed simultaneously or separately”.
The measurement of the impedance at the first frequency and second frequency can only be done either simultaneously or separately. There are no other alternatives. The measurement of impedance using the first frequency and the second frequency is already recited by claim 1, therefore, claims 11 and 13 are not further limiting the claim that they depend on.
Applicant may cancel the claims, amend the claims to place the claims in proper dependent form, rewrite the claims in independent form, or present a sufficient showing that the dependent claims comply with the statutory requirements.
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 16 is rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more.
The U.S. Patent and Trademark Office recently revised the MPEP with regard to § 101
(see the MPEP at 2106). Regarding the MPEP at 2106, in determining what concept the claim is
"directed to," we first look to whether the claim recites:
(1) any judicial exceptions, including certain groupings of abstract ideas (i.e.,
mathematical concepts, certain methods of organizing human activity such as a
fundamental economic practice, or mental processes); and
(2) additional elements that integrate the judicial exception into a practical
application (see MPEP § 2106.05(a)-(c), (e)-(h)).
Only if a claim (1) recites a judicial exception and (2) does not integrate that exception
into a practical application, do we then look to whether the claim contains an "'inventive
concept' sufficient to 'transform"' the claimed judicial exception into a patent-eligible
application of the judicial exception. Alice, 573 U.S. at 221 (quoting Mayo, 566 U.S. at 82). In so
doing, we thus consider whether the claim:
(3) adds a specific limitation beyond the judicial exception that is not "well-understood, routine, conventional" in the field (see MPEP § 2106.0S(d)); or
(4) simply appends well-understood, routine, conventional activities previously
known to the industry, specified at a high level of generality, to the judicial exception.
See MPEP 2106.
ELIGIBILITY STEP 2A: WHETHER A CLAIM IS DIRECTED TO A JUDICIAL EXCEPTION
Step 2A, Prong 1
Claim 16 is directed to an abstract idea. Claim 16 recites, “the impedance of the antibody and the impedance of the antigen-antibody have the relational expression below:
[AltContent: textbox ([img-media_image1.png])]
(where, Z denotes the impedance, Rs denotes a solution resistance, Rb denotes a resistance between the bead and the electrode, Cb denotes a capacitance between the bead and the electrode, and Cdl denotes a capacitance between the electrodes)”. Claim 16’s relational expression is an abstract idea, namely a mathematical formula.
Step 2A, Prong 2
Claim 16 depends on Independent claim 1, which recites the following steps: “loading an antibody into a biosensor device”, “measuring an impedance of the antibody”, “performing an antigen-antibody reaction”, “measuring an impedance of antigen-antibody”, and “calculating an impedance change”. Such steps are insufficient to integrate the judicial exception into a practical application because the purpose is merely to obtain data. These steps do not go beyond insignificant pre-solution activity, i.e., a mere data gathering step necessary to use the judicial exception.
The purpose of these additional limitations is merely to obtain the data used for the mathematical concepts. As such, these limitations fail to amount to an integration into a practical application. None of these recited steps apply, rely on, or use the judicial exception in a manner that imposes a meaningful limit on the judicial exception.
ELGIBILITY STEP 2B: WHETHER THE ADDITIONAL ELEMENTS CONTRIBUTE AN “INVENTIVE CONCEPT”
Further, the additional elements of the claims (the active method steps/limitations recited in addition to the judicial exceptions themselves) do not add significantly more to the judicial exceptions; the additional recited claim elements are recited at a high level of generality, and are not, for example limited to any particular antibody or biosensor as claimed.
Furthermore, Shin (“Sensitivity Enhancement of Bead-based Electrochemical Impedance Spectroscopy (BEIS) biosensor by electric field-focusing in microwells”, published 2016-11-15) supports that the steps of “loading an antibody into a biosensor device”, “measuring an impedance of the antibody”, “performing an antigen-antibody reaction”, “measuring an impedance of antigen-antibody”, and “calculating an impedance change” were routine and conventional activity previously performed by those of skill in the art. It does not appear to be the case that the active steps recited, which are performed in order to gather the data or perform the assay, are steps recited or performed in an unconventional or non-routine way, such as to provide an inventive concept under step 2B.
The claimed limitations as currently presented fail to recite limitations that add a feature that is more than well-understood, conventional, or routine in the field of diagnostics and biochemical assay methodologies.
Mathematical formulas, which represent abstract ideas, are not themselves patentable. The claims fail to set forth additional steps or elements that would amount to significantly more. A process of using equations would need to integrate the equations into the process, as a whole, using additional steps that are not already conventional; and which are sufficient to narrow the scope of the claim so that others are not foreclosed from using the equations in different applications.
For all of these reasons, the claims fail to include additional elements that are sufficient to either integrate the judicial exception into a practical application thereof, or amount to significantly more than the judicial exception.
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.
Claims 1-4, 6-7, and 9-15, and 17 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Shin (“Sensitivity Enhancement of Bead-based Electrochemical Impedance Spectroscopy (BEIS) biosensor by electric field-focusing in microwells”, published 2016-11-15).
With respect to claims 1, 11, and 13, Shin teaches a method by which biosensor device detects antigen by using multiple frequencies, comprising:
loading an antibody into a biosensor device including a micro-well;
measuring an impedance of the antibody with respect to each of a first frequency and a
second frequency;
performing an antigen-antibody reaction by injecting an antigen into the biosensor device;
measuring an impedance of antigen-antibody linked by the antigen-antibody reaction using each of the first frequency and the second frequency; and
calculating an impedance change according to the antigen-antibody reaction from the
impedance of the antigen-antibody with respect to the first frequency and the impedance of the antigen-antibody with respect to the second frequency (see, e.g., loading an antibody into a micro-well – p. 18, under “Fig. 1”, under panel “(b)”; measuring the impedance of the antibody with respect to each of a first and a second frequency – p. 21, under “Fig. 4.”, panel “(b)”, see below, and p. 17, col. 1, para. 2: “While the magnetic beads of the antibody coating are trapped in the microwells, a sample is injected and the reaction with antigens occurs changes in the impedance of the surfaces of the beads, and makes the difference with the beads incubated in a negative control sample”; injecting an antigen into the biosensor - p. 18, under “Fig. 1”, under panel “(b)”, see below; measuring an impedance of antigen-antibody linked by the antigen-antibody reaction using each of the first and second frequency - p. 21, under “Fig. 4.”, panel “(b)”, see below; calculating an impedance change according to the antigen-antibody reaction – p. 16, under “ABSTRACT”: “The experimental results showed that a low concentration of PSA (a few tens or hundreds of fg/mL) were detectable as a ratio of the changes in the impedance of the PBS buffer or in human plasma”).
With respect to claim 2, Shin teaches calculating a first normalized impedance by normalizing a first antigen-antibody impedance measured with respect to the first frequency of the antigen-antibody;
calculating a second normalized impedance by normalizing a second antigen-antibody
impedance measured with respect to the second frequency of the antigen-antibody; and
calculating an impedance change value according to the antigen-antibody reaction using
the first normalized impedance and the second normalized impedance (see, e.g., p. 22, para. spanning col. 1 to col. 2: “To resolve the variation of sensitivity due to differences from device to device, we defined a normalized sensitivity as the ratio of impedance changes at a concentration of PSA antigen normalized by the initial reference impedance as: [AltContent: textbox ([img-media_image2.png])]
where, ZPSA and ZBuffer are the impedances at a concentration of PSA antigen in buffer solution and the impedance in only buffer solution, respectively”).
With respect to claim 3, Shin teaches wherein the calculating of the first normalized impedance is performed by dividing the first antigen-antibody impedance by a maximum value of a first antibody impedance measured using the first frequency for the antibody and normalizing the first antigen-antibody impedance (see, e.g., p. 22, para. spanning col. 1 to col. 2: “To resolve the variation of sensitivity due to differences from device to device, we defined a normalized sensitivity as the ratio of impedance changes at a concentration of PSA antigen normalized by the initial reference impedance as: [AltContent: textbox ([img-media_image2.png])]
where, ZPSA and ZBuffer are the impedances at a concentration of PSA antigen in buffer solution and the impedance in only buffer solution, respectively”).
With respect to claim 4, Shin teaches wherein the calculating of the second normalized impedance is performed by dividing the second antigen-antibody impedance by a maximum value of a second antibody impedance measured using the second frequency for the antibody and normalizing the second antigen-antibody impedance, as in claim 4 (see, e.g., p. 22, para. spanning col. 1 to col. 2: “To resolve the variation of sensitivity due to differences from device to device, we defined a normalized sensitivity as the ratio of impedance changes at a concentration of PSA antigen normalized by the initial reference impedance as: [AltContent: textbox ([img-media_image2.png])]
where, ZPSA and ZBuffer are the impedances at a concentration of PSA antigen in buffer solution and the impedance in only buffer solution, respectively”, and p. 21, under “Fig. 4.”, panel “(b)”, see below).
With respect to claim 6, Shin teaches performing the antigen-antibody reaction and the measuring of the impedance of the antigen-antibody are repeatedly performed
while changing a concentration of the antigen (see, e.g., p. 21, under “Fig. 4.”, panel “(b)”, see below).
With respect to claim 7, Shin teaches after the performing of the antigen-antibody reaction, performing cleaning to remove a non-specific conjugate using a cleaning solution (see, e.g., p. 17, col. 2, under “2.3. Experimental procedures and electrical measurement for PSA detection”: “After reaction between the anti-PSA antibody and antigen, the PBS buffer was used to remove non-specific binding for a few minutes”).
With respect to claim 9, Shin teaches wherein the loading of the antibody is performed
by loading a bead to which the antibody is linked into the biosensor device (see, e.g., p. 18, under “Fig. 1”, under panel “(b)”, see below).
With respect to claims 10 and 12, Shin teaches measuring the impedance of the antibody and the antibody-antigen complex under a flow phosphate buffered saline (see, e.g., p. 18, under “Fig. 1.”, under panel “(a)”, under “Microfluidic channel”, see below, and p. 17, col. 2, under “2.3. Experimental procedures and electrical measurement for PSA detection”: “After reaction between the anti-PSA antibody and antigen, the PBS buffer was used to remove nonspecific binding for a few minutes. The impedance of the BEIS platform was measured”).
With respect to claim 14, Shin teaches wherein the first frequency ranges from 1 Hz to
100 Hz, and the second frequency ranges from 500 Hz to 2,000 Hz (see, e.g., p. 21, under “Fig. 4.”, panel “(b)”, see below).
With respect to claim 15, Shin teaches wherein the impedance of the antibody and the impedance of the antigen-antibody are measured by applying a voltage ranging from 1 mV to 500mV (see, e.g., p. 18, col. 2, para. 1: “During the frequency sweeping, the frequency was varied from 1 Hz to 1 MHz, while the amplitude of voltage was fixed at 50 mVrms”).
With respect to claim 17, Shin teaches wherein the micro-well includes a substrate constituting a bottom surface,
a working electrode and a counter electrode are formed on one surface of the substrate, and
a passivation layer forming a well-shaped inner space that isolates the antibody from an
outside and accommodates the antibody is provided on an upper portion of each of the working electrode and the counter electrode (see, e.g., p. 18, under “Fig. 1.”, see below, and p.19, under “Fig. 2.”, panel “(c)”, see below, and p. 21, col. 1, under “3.2. Control experiments with magnetic beads”: “the SU-8 passivation surface”).
[AltContent: textbox ([img-media_image3.png]
Shin, Fig. 1.)][AltContent: textbox ([img-media_image4.png]
Shin, Fig. 2., panel “(c)”)][AltContent: textbox ([img-media_image5.png]
Shin, Fig. 4., panel “(b)”)]
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 5 is rejected under 35 U.S.C. 103 as being unpatentable over Shin (cited above) as applied to claims 1-4, 6-7, and 9-17 above, and further in view of Plaxco (WO 2018223024 A2, published 2018-12-06).
Shin teaches as set forth above, but fails to teach wherein the calculating of the impedance change value according to the antigen-antibody reaction using the first normalized impedance and the second normalized impedance is performed by:
dividing the first normalized impedance by the second normalized impedance;
dividing the second normalized impedance by the first normalized impedance;
subtracting the second normalized impedance from the first normalized impedance; or
subtracting the second normalized impedance from the first normalized impedance, as in claim 5.
However, Plaxco teaches wherein the calculating of the impedance change value according to the antigen-antibody reaction using the first normalized impedance and the second normalized impedance is performed by:
dividing the first normalized impedance by the second normalized impedance, as in claim 5 (see, e.g., para. [0053]: “The inventors of the present disclosure have determined that there is a constant ratio, α, between the current observed at the non-responsive frequency, iNR, and the current observed in a target-free sample, i0. Like KD and γ this ratio is based on the inherent electron transfer kinetics of a particular sensor design and, under consistent operating conditions, will be constant and stable for all sensors having the same design. Advantageously, this previously unknown relationship enables the measurement of iNR to be used in the calculation of imin”).
Shin and Plaxco are analogous to the field of the claimed invention because they are both in the field of electrochemical biosensors. One of ordinary skill in the art before the effective filing date of the application would have found it obvious to incorporate the frequency-dependent normalization of Plaxco into the assay of Shin. An artisan would have been motivated to do so because Plaxco discloses, “determination of imin for an individual sensor is often not practical, a method is needed to estimate imin to avoid the need for individual sensor calibration. The inventors of the present disclosure have advantageously discovered a methodology for accurately and easily calculating imin values for sensors of a common class. The novel methods of the invention are based upon the strong frequency dependence of electrochemical sensing outputs” (see, Plaxco, para. [0051]). An artisan would have had a reasonable expectation of success based on the given disclosures.
Claim 8 is rejected under 35 U.S.C. 103 as being unpatentable over Shin (cited above), as applied to claims 1-4, 6-7, and 9-17 above, as evidenced by the product information for Boston Bioproducts Phosphate Buffered Saline-Tween, PBST (10X, with 1% Tween-20, pH 7.4) - 1L (Catalog No.NC9235652, https://www.fishersci.com/shop/products/pbs-with-tween-20/NC9235652#).
Shin teaches as set forth above, including teaching washing/cleaning with phosphate buffered saline (PBS), as in claim 8 (see, e.g., p. 17, col. 2, under “2.3. Experimental procedures and electrical measurement for PSA detection”: “After reaction between the anti-PSA antibody and antigen, the PBS buffer was used to remove nonspecific binding for a few minutes”). But, Shin fails to explicitly teach washing/cleaning with phosphate buffered saline comprising 0.05 wt% to 0.2 wt% stearic acid ester of polyoxyethylene sorbitan, as in claim 8. The applicant’s specification discloses that stearic acid ester of polyoxyethylene sorbitan is equivalent to the commonly used surfactant, Tween. See p. 15, line 6 of the applicant’s specification.
While Shin does not wash with PBS comprising Tween, an artisan would have been motivated to do so because Boston Bioproducts provides evidence that “Phosphate Buffered Saline with Tween-20 (PBST) is a specialized variant of PBS, supplemented with Tween-20, a non-ionic surfactant. Tween-20 minimizes the non-specific binding and background noise, resuting [sic] in enhanced signal to noise ratio. PBST is often used in immunoassays” (see, p. 1, para. 1). The working concentration of Tween-20 in the product of Boston Bioproducts is 0.1%, as in claim 8. PBST is a well-known surfactant with well-known benefits. Using PBST in the assay of Shin does not go beyond routine optimization. The use of PBST in the assay of Shin results in predictable benefits that would be expected by an artisan with ordinary skill in the art. An artisan would have had a reasonable expectation of success based on the given disclosures.
Conclusion
No claims are allowed.
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/MICHAEL CAMERON SVEIVEN/Examiner, Art Unit 1678
/GREGORY S EMCH/Supervisory Patent Examiner, Art Unit 1678
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