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 .
Status of the Claims
Claims 1-10, 18, and 20-24 are pending in the application and are the subject of this office action.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 6 February 2025 has been entered.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 6 February 2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the examiner.
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-10 and 18 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Independent claim 1 recites “to quantify the prostate-specific biomarker in the blood at levels suitable for use of the prostate-specific biomarker as an indicator of prostate cancer”, but the application as originally filed does not support this limitation of the claims. What exactly is included in the genus of “prostate-specific biomarker” is not explicitly clear, and what level a given “prostate specific biomarker” would need to be detected at in order to serve as an indicator of prostate cancer is not clear. The specification provides some clarification for PSA (Par. 44: PSA test methods according to the present teachings can measure the level of PSA (e.g. ng/mL) in the serum of a man. The blood level of PSA can be used as a potential indicator for prostate cancer. In addition to prostate cancer, a number of benign (not cancerous) conditions such as an enlarged or inflamed prostate can also cause a man’s PSA level to increase) but provides only a unit of concentration (ng/mL) which does not provide any specific indication of what level of PSA would be quantified to be used as an indicator of prostate cancer.
Regarding other prostate-specific biomarkers, the specification indicates a list of other biomarkers which may be detected and which may be associated with prostate disease (Par. 44: other biomarkers such as kallikrein related peptidase 2, PCA3, TMPRSS2-ERG gene fusion and the like can be used as potential indicators for prostate disease), but these are not explicitly linked to or described as indicators of prostate cancer, and again, it is not clear what level of each biomarker would be a suitable indicator of prostate cancer, and it is not clear what other biomarkers are encompassed by the phrasing “and the like”. The specification provides no specific example or data to show that the different biomarkers are detected in the claimed quantities (or in any particular quantity), and provides no specific example or quantitative data to evidence a particular range or limit of detection for the sensor as a whole or for any given biomarker. The specification also does not provide evidence or showing that defines a particular range of quantification of the biomarker or a particular limit of detection of the biomarker on the device.
This is a new matter rejection.
Claim Rejections - 35 USC § 112(b)
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 1-10, 18, and 20-24 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.
Claims 1, 18, 20, and 22 are rejected as indefinite because of the recitation of a “prostate-specific biomarker”. This is indefinite because the metes and bounds of the term are unclear, i.e. the criteria required in order for a given biomarker to be considered “prostate-specific” are not defined. The specification provides (Par. 6: the prostate-specific biomarker can be a prostate specific antigen (PSA). In other embodiments, the prostate-specific biomarker can be kallikrein-related peptidase 2, PCA3, TMPRSS2 gene fusion, or the like; see also Par. 44), but does not explicitly limit or define a prostate-specific biomarker (i.e. the listing of potential biomarkers concludes with “and the like” but it is not clear what other species are included or how exactly one would determine what other species are included).
Claim 1 further recites “so as to quantify the prostate-specific biomarker in the blood at levels suitable for use of the prostate-specific biomarker as an indicator or prostate cancer”. This is indefinite both because the scope of biomarkers included in “prostate-specific biomarker” is unclear, and also because what comprises a level of a given biomarker “suitable for use of the prostate specific biomarker as an indicator of prostate cancer” is not clearly defined (i.e. it is not clearly defined in the claim for any particular biomarker, and also cannot be definitively determined for the entire scope of the claim since the entire scope of biomarkers included in the recited genus is not definitely defined).
Claim 1 is vague regarding “said electrical data”. There is no prior introduction of “electrical data” in the claim, therefore there is insufficient antecedent basis for this limitation in the claim.
Claim 18 is rejected as indefinite because it is unclear if claim 18 is intended to set forth an entirely new structural component of the recited sensor, or if it simply applies limitation/intended use of a previously recited structure (i.e. as a calibration sensor or as a component of a calibration sensor). That is, the calibration sensor is recited to contain only structural features which are already recited in the sensor as a whole in independent claim 1. It is unclear, for example, whether the “graphene layer deposited on an underlying substrate” recited as part of the calibration sensor in claim 18 is different than the “graphene layer deposited on an underlying substrate” recited in independent claim 1. Clarification is required
Claim 20 is vague regarding “the first graphene layer”. There is no prior introduction of “a first graphene layer”, therefore there is insufficient antecedent basis for this limitation in the claims.
Claim 23 is rejected as indefinite because the metes and bounds of the claim are unclear. The phrasing of the claim as a whole and the fact that the penultimate and ultimate member of the list are not joined by any particular conjunction (i.e. “and”, “or”, or “and/or”) makes it unclear whether the claim is limited to an embodiment of the sensor which comprises test sensing elements configured for detection of all species recited in claim 23 (as if the species were joined by “and”) or only one (or more) of the species recited in claim 23 (as if the species were joined by “or” or “and/or”). To give the claim its broadest reasonable interpretation, the species are interpreted herein as if they are joined by the conjunction “and/or” since this is the broadest option. Clarification is required.
Dependent claims 2-10, 18, and 21-24 are rejected as indefinite because they depend from indefinite independent claims and fail to remedy their deficiencies.
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.
Claims 1-9, 18, and 20-21 are rejected under 35 U.S.C. 103 as being unpatentable over Nawana et al (WO 2019/227069 A1) in view of Li et al (Label electrochemical immunosensor for prostate-specific antigen based on graphene and silver hybridized mesoporous silica; previously cited).
Regarding claims 1-2, and 7-9 Nawana teaches a sensor for detecting a target analyte (Abstract), comprising:
A graphene layer deposited on an underlying substrate (Pg. 6, last Par.-Pg. 7, first Par: sensor for detecting an analyte in a sample which comprises a graphene layer; Pg. 7, Par. 5: graphene layer can be deposited on a semiconductor substrate such as a silicon substrate).
A plurality of antibodies couple to the graphene layer to generate an antibody-functionalized graphene layer, wherein the antibodies exhibit specific binding to a target analyte (Pg. 6, last Par. -Pg. 7, first Par.: a plurality of antibodies coupled to said graphene layer, said antibodies exhibiting specific binding to said analyte).
A plurality of electrical conductors electrically coupled to the antibody-functionalized graphene layer for measuring an electrical resistance of the graphene layer (Pg. 7, first Par.; Pg. 4, Par. 2: a plurality of electrical conductors are coupled to the functionalized graphene layer for measuring an electrical property of that layer in response to interaction of the layer with a sample. For example, the electrical property may be the DC electrical resistance of the functionalized graphene layer); and
An analyzer having a data acquisition unit configured to acquire said electrical data and an analysis module for processing the acquired electrical data to measure an electrical resistance of the graphene layer so as to quantify the biomarker in blood (Pg. 3, Par. 4: an analyzer can be coupled to the sensor for receiving data from the test sensing unit and the calibration sensing unit and operating on said data to quantify the amount of the biomarker in the biological sample; Pg. 12, last Par-Pg. 13, first Par.; Pg. 1, Par. 2: sample may be a blood sample, e.g. plasma sample).
Nawana teaches that analytes can be detected in a sample at concentrations as low as 1 pg/mL (Pg. 17, Par. 2: a sensor according to the present teachings can detect any of the above analytes at a concentration as low as 1 pg/mL).
Nawana does not explicitly teach the sensor wherein the antibodies exhibit specific binding to a prostate specific biomarker, such as PSA, however Nawana does teach that the biomarker detected by the disclosed sensor may be a protein analyte which is not particularly limited (Pg. 7, Par. 4: analyte may comprise an allergen, protein, gluten protein, pathogen, bacteria, virus; Pg. 5-6).
Regarding claims 1-2, Li teaches an electrochemical immunosensor for the detection of PSA comprising a graphene layer disposed on a substrate, wherein the graphene layer is functionalized with anti-PSA antibodies and is coupled to a plurality of electrodes (Abstract: an electrochemical immunosensor for PSA detection using the amino-functionalized graphene sheet -ferrocenecarboxyaldehyde composite material (NH2-GS@FCA); Fig. 1 shows the graphene layer deposited on an electrode substrate and functionalized with antibody Ab1; Pg. 77, Col. 1, Par. 3: The antibody Ab1 may be anti-PSA antibody. Electrochemical measurements were made with a conventional three-electrode system employing a working electrode, reference electrode, and counter electrode).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the sensor taught by Nawana to use anti-PSA antibodies for the detection of the prostate-specific biomarker PSA, as taught by Li, because the sensor of Nawana is not limited to functionalization with a specific species of antibody, and one of ordinary skill in the art would use the appropriate antibody to detect the desired analyte, such as the anti-PSA antibody of Li for the detection of PSA. Additionally, one would have been motivated to modify the sensor for the detection of PSA because Li teaches that PSA is a biomarker that is known in the art to be clinically important for the detection and diagnosis of prostate cancer (Li, Abstract). One of ordinary skill in the art would have a reasonable expectation of success in making this modification because both Nawana and Li disclose sensor devices comprising a graphene layer disposed on a substrate and functionalized with antibodies that specifically bind to a target analyte, and because Nawana teaches that the disclosed sensor has a limit of detection (i.e. pg/mL) which encompasses the critical concentration ranges of PSA detected in Li (i.e. ng/mL).
Since Li teaches that PSA measured on the order of ng/mL in a blood sample can be used as an indicator of prostate cancer (Pg. 76, Col. 1, Par. 1) and since Nawana teaches a sensor which can detect as low as 1 pg/mL of analyte in a sample, the modified device of Nawana in view of Li is understood to read on the limitation of claim 1 “to quantify the prostate-specific biomarker in the blood at levels suitable for use of the prostate-specific biomarker as an indicator of prostate cancer”.
Regarding claim 3 Nawana further teaches the sensor comprising a reference electrode disposed in proximity of the antibody-functionalized graphene layer (Pg. 6, last Par.-Pg. 7, first Par.: the sensor comprises a reference electrode disposed in the vicinity of the antibody-functionalized graphene layer).
Regarding claim 4, Nawana further teaches the sensor comprising an AC voltage source for applying an AC voltage to the reference electrode (Pg. 6, last Par.-Pg. 7, first Par.: An AC voltage source is provided for applying an AC voltage to said reference electrode).
Regarding claim 5, Nawana further teaches the sensor wherein the AC voltage has a frequency in a range of about 1 kHz to about 1 MHz (Pg. 7, Par. 2).
Regarding claim 6, Nawana further teaches the sensor wherein the AC voltage has an amplitude in a range of about 100 mV to about 3 V (Pg. 7, Par. 2).
Regarding claim 18, Nawana further teach the sensor comprising a calibration sensor, wherein the calibration sensor comprises:
A graphene layer deposited on an underlying substrate; and a plurality of antibodies coupled to the graphene layer of the calibration sensor to generate an antibody-functionalized graphene layer of the calibration sensor, wherein the antibodies exhibit specific binding to said prostate-specific biomarker (Pg. 3, Par. 2: the sensor comprising a test sensing unit and a calibration unit. The calibration unit is configured for receiving a calibration sample for providing calibration data for use in quantifying the biomarker detected by the sensing unit. Each of the test sensing unit and the calibration sensing unit comprises a graphene layer disposed on an underlying substrate, and a plurality of antibodies coupled to said graphene layer wherein said antibodies exhibit specific binding to said biomarker, and a plurality of electrical conductors electrically coupled to said functionalized graphene layer for measuring an electrical property of said functionalized graphene layer).
Regarding claims 20-21, Nawana teaches a sensor comprising:
At least one test sensing element comprising a graphene layer deposited on an underlying substrate and a plurality of antibodies coupled to the first graphene layer to generate a first antibody-functionalized graphene layer, wherein the antibodies exhibit specific binding to a biomarker; and at least one calibration sensing element comprising a graphene layer deposited on an underlying substrate and a plurality of antibodies coupled to the graphene layer of the at least one calibration sensing element to generate an antibody-functionalized graphene layer of the calibration sensing element, wherein the antibodies exhibit specific binding to a biomarker; wherein an electrical signal generated by the at least one calibration sensing element in response to contact with a calibration sample can be employed for quantifying an amount of the biomarker measured by said at least one test sensing element (Pg. 3, Par. 2: the sensor comprising a test sensing unit and a calibration unit. The calibration unit is configured for receiving a calibration sample for providing calibration data for use in quantifying the biomarker detected by the sensing unit. Each of the test sensing unit and the calibration sensing unit comprises a graphene layer disposed on an underlying substrate, and a plurality of antibodies coupled to said graphene layer wherein said antibodies exhibit specific binding to said biomarker, and a plurality of electrical conductors electrically coupled to said functionalized graphene layer for measuring an electrical property of said functionalized graphene layer).
Nawana teaches that analytes can be detected in a sample at concentrations as low as 1 pg/mL (Pg. 17, Par. 2: a sensor according to the present teachings can detect any of the above analytes at a concentration as low as 1 pg/mL).
Nawana does not explicitly teach the sensor wherein the antibodies exhibit specific binding to a prostate specific biomarker, such as PSA, however Nawana does teach that the biomarker detected by the disclosed sensor may be a protein analyte which is not particularly limited (Pg. 7, Par. 4: analyte may comprise an allergen, protein, gluten protein, pathogen, bacteria, virus; Pg. 5-6).
Regarding claims 20-21, Li teaches an electrochemical immunosensor for the detection of PSA comprising a graphene layer disposed on a substrate, wherein the graphene layer is functionalized with anti-PSA antibodies and is coupled to a plurality of electrodes (Abstract: an electrochemical immunosensor for PSA detection using the amino-functionalized graphene sheet -ferrocenecarboxyaldehyde composite material (NH2-GS@FCA); Fig. 1 shows the graphene layer deposited on an electrode substrate and functionalized with antibody Ab1; Pg. 77, Col. 1, Par. 3: The antibody Ab1 may be anti-PSA antibody. Electrochemical measurements were made with a conventional three-electrode system employing a working electrode, reference electrode, and counter electrode).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the sensor taught by Nawana to use anti-PSA antibodies for the detection of the prostate-specific biomarker PSA, as taught by Li, because the sensor of Nawana is not limited to functionalization with a specific species of antibody, and one of ordinary skill in the art would use the appropriate antibody to detect the desired analyte, such as the anti-PSA antibody of Li for the detection of PSA. Additionally, one would have been motivated to modify the sensor for the detection of PSA because Li teaches that PSA is a biomarker that is known in the art to be clinically important for the detection and diagnosis of prostate cancer (Li, Abstract). One of ordinary skill in the art would have a reasonable expectation of success in making this modification because both Nawana and Li disclose sensor devices comprising a graphene layer disposed on a substrate and functionalized with antibodies that specifically bind to a target analyte, and because Nawana teaches that the disclosed sensor has a limit of detection (i.e. pg/mL) which encompasses the critical concentration ranges of PSA detected in Li (i.e. ng/mL).
Claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over Nawana et al (WO 2019/227069 A1) and Li et al (Label electrochemical immunosensor for prostate-specific antigen based on graphene and silver hybridized mesoporous silica; previously cited), as applied to claim 1 above, and further in view of Shang et al (Catalyst-free efficient growth, orientation, and biosensing properties of multilayer graphene nanoflake films with sharp edge planes; previously cited).
Regarding claim 10, Nawana in view of Li teaches the sensor of claim 1, as described above, but does not explicitly teach the sensor wherein the graphene layer comprises a plurality of graphene nano-flakes.
Shang is directed to strategies for the efficient synthesis of multilayer graphene nanoflake films (MGNFs) which may be used in biosensors (Abstract).
Regarding claim 10, Shang teaches a biosensor comprising a MGNF deposited on a silicon substrate (Pg. 3513, Col. 2, Par. 2: demonstrates a method of efficiently growing MGNFs on Si substrates). Shang teaches that biosensing electrodes comprising MGNF provide enhanced biosensing performance and are readily amenable to functionalization (Pg. 3513, Col. 2, Par. 2).
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 sensor taught by Nawana in view of Li to use a graphene layer comprising graphene nano-flakes such as those taught by Shang because Shang teaches that MGNFs are applicable to biosensing electrodes and that they demonstrate superior biosensing performance compared to other carbon based electrodes (Pg. 3513, Col. 2, Par. 2: MGNFs demonstrate superior biosensing performance to other untreated carbon based electrode. The remarkable ET kinetics, active electrocatalysis, and sensitive sensing properties of MGNFs are mainly due to edge plane sites/defects that occur at the end of the vertical graphene nanoflakes). One of ordinary skill in the art would have a reasonable expectation of success in making this modification because both Nawana and Shang disclose biosensing electrodes comprising a graphene layer disposed on a silicon substrate which can be functionalized.
Claims 22-24 is/are rejected under 35 U.S.C. 103 as being unpatentable over Nawana et al (WO 2019/227069 A1) and Li et al (Label electrochemical immunosensor for prostate-specific antigen based on graphene and silver hybridized mesoporous silica; previously cited) as applied to claims 20-21 above, and further in view of Lee et al (A Highly Sensitive Porous Silicon (P-Si)-Based Human Kallikrein 2 (hK2) Immunoassay Platform toward Accurate Diagnosis of Prostate Cancer. Sensors (Basel). 2015 May 22;15(5):11972-87.).
Nawana in view of Li teaches the sensor of claims 20-21 as described above, wherein the modified sensor comprises a graphene layer functionalized with anti-PSA antibodies.
Regarding claims 22-23, Nawana teaches the sensor wherein said at least one test sensing element comprises a plurality of test sensing elements, wherein each of said plurality of test sensing elements is configured for detection of one of a plurality of different biomarkers (Pg. 6, Par. 2: sensor may comprise a plurality of sensing elements where each of the sensing elements comprises a graphene layer disposed on an underlying substrate. At least one of the sensing elements comprises a graphene layer functionalized for a first biomarker and least another one of the sensing elements comprises a graphene layer functionalized with a plurality of antibodies exhibiting a specific binding to a second biomarker).
The sensor of Nawana in view of Li comprises a graphene layer functionalized with anti-PSA antibodies. Though Nawana further teaches that the sensor may comprise a plurality of test sensing elements configured for detection of different biomarkers, as described above, Nawana does not explicitly teach test sensing elements configured for detection of a plurality of prostate specific biomarkers comprising PSA, KLK2, PCA3, and/or TMPRSS2-ERG gene fusion.
Regarding claims 22-23, Lee teaches that levels of human kallikrein 2 (i.e. kallikrein-like peptidase 2, KLK2) detected in a sample can be used to aid in the diagnosis of prostate cancer (Abstract). Lee teaches that KLK2 can be detected in a sample using an immunoassay comprising a surface functionalized with anti-KLK2 antibodies (Abstract). Lee further teaches that KLK2 and PSA are biomarkers that can be used in combination to improve prediction of prostate cancer (Pg. 11983, Par. 1: Recent studies report that the level of KLK2 in combination with total PSA or free PSA might improve prediction of prostate cancer stage and risk of biochemical cancer recurrence after radical prostatectomy. Detection of KLK2 down to a limit of 1 pg/mL as described in the experiment could contribute to future clinical practice by enabling more accurate diagnosis of prostate cancer patients).
Therefore it would have been obvious to one of ordinary skill in the art before the effective filing date of the claim invention to have modified the sensor of Nawana in view of Li such that the plurality of test sensing elements would include one or more test sensing elements configured for the detection of KLK2, by functionalizing the graphene layer with the anti-KLK2 antibody taught by Lee. One of ordinary skill in the art would be motivated to make this modification because Lee teaches that measurement of KLK2 can aid in the diagnosis of prostate cancer, particularly when used in combination with the measurement of PSA. One of ordinary skill in the art would have a reasonable expectation of success in making this modification because Nawana discloses a sensor which comprises a plurality of test sensing elements comprising graphene layers which can be functionalized with different antibodies for the detection of different biomarkers.
Regarding claim 24, Nawana further teaches the sensor wherein said at least one calibration sensing element comprising a plurality of calibration sensing elements wherein each of said plurality of calibration sensing elements is associated with one of said plurality of test sensing elements. That is, Nawana teaches the sensor comprising a test sensing element and an associated calibration sensing element which are functionalized by antibodies which specifically bind to the same target analyte, and teaches that the calibration sensing element is used with a calibration sample with known analyte concentration, such that signal from a testing sensing element obtained from a test sample with unknown analyte content can be compared to signal from a calibration sensing element obtained from a calibration sample with known analyte content to determine presence and/or quantity of the analyte in the test sample (Pg. 3, Par. 2). Nawana further teaches that the sensor may comprise a plurality of test sensing elements for detecting a plurality of different markers (Pg. 6, Par. 2). Nawana further teaches that each test sensing element may be associated with one or more calibration sensing elements functionalized with antibodies which specifically bind to the same biomarker as the test sensing elements, wherein different standard samples containing different and known concentrations of the biomarker can be applied to different calibration sensing elements in order to produce a standard curve by which to quantify the biomarker present in the test sample applied to the test sensing element (Pg. 14, Par. 2-3).
As such, It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to either conclude that the teachings of Nawana encompass an embodiment wherein the sensor comprises a plurality of calibration sensing elements, wherein each of said plurality of calibration sensing elements is associated with one of said plurality of test sensing elements or to modify the sensor of Nawana to meet this limitation. Since Nawana teaches a sensor comprising a plurality of calibration sensing units and a plurality of test sensing units as discussed above, an embodiment wherein each different biomarker detected by each of the plurality of test sensing units can also be detected on an associated calibration sensing unit would provide the obvious utility of allowing a user to collect calibration data for each different biomarker detected by each different test sensing unit. One of ordinary skill in the art would have a reasonable expectation of success because Nawana teaches the sensor comprising a plurality of sensing units which each comprise an antibody-functionalized graphene layer and teaches that each sensing unit may be modified with antibodies which bind either the same biomarker (as in a test sensing unit and its associated calibration unit as described on Pg. 3) or different biomarkers (as in different testing units configured for the detection of different biomarkers, as described on Pg. 6),
It is further noted that in all its recitations in the instant claims (i.e. claims 18, 20, 24), a calibration sensing element is structurally identical to a test sensing element (i.e. a graphene layer disposed on a substrate and functionalized with an antibody), such that the only distinction between the two is a matter of intended use (i.e. whether a calibration sample or a test sample is applied to the sensing element during the process of using the device). Though the intended use of calibration is addressed in the rejections of these claims, this is provided only for the purpose of compact prosecution of the claims, and it is noted that a recitation of intended use does not distinguish the claims over the prior art in a claim to a sensor. As such, the teaching of Nawana that the sensor may comprise multiple test sensing elements configured for the detection of the same analyte (as implied by Pg. 6, Par. 2) would be sufficient to read on both a test sensing element and a calibration sensing element for that particular analyte, regardless of whether one is taught to be used for calibration or not.
Further as it applies to claim 24, the claim is only limited in the sense that it requires at least two sensing elements (of a plurality of sensing elements) which are configured for the detection of the same analyte (i.e. there is no structural difference between a test sensing element and a calibration sensing element for the same biomarker, and the recitation that one sensing element be “associated with” another could be met simply by their existence on the same device).
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-9, 18, and 20-21 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 25, 30, and 32-33 of copending Application No. 18/794,968 in view of Nawana et al (WO 2019/227069 A1) and Li et al (Label electrochemical immunosensor for prostate-specific antigen based on graphene and silver hybridized mesoporous silica; previously cited).
All limitations of instant claims 1-2 and 7 are taught by reference claim 25, with the exception that the reference claim teaches functionalization of the graphene layer with different antibodies, the reference claim does not teach an analyzer, and the reference claim does not specifically teach that the electrical property measured is resistance.
Regarding instant claims 1-2 and 7, Nawana teaches a sensor comprising a graphene layer disposed on a substrate and functionalized with antibodies which specifically bind to a target biomarker (Abstract). Nawana further teaches the sensor comprising at least one pair of electrically conductive pads couple to antibody functionalized graphene layer for measuring an electrical property, wherein the electrical property measured is resistance ()(Pg. 7, first Par.; Pg. 4, Par. 2: a plurality of electrical conductors are coupled to the functionalized graphene layer for measuring an electrical property of that layer in response to interaction of the layer with a sample. For example, the electrical property may be the DC electrical resistance of the functionalized graphene layer).
It would have been obvious to one of ordinary skill in the art to have modified the sensor taught by the reference claims such that the electrically conductive pads of the reference claim measure resistance as taught by Nawana. One would be motivated to make this modification because Nawana teaches that measurement of resistance can facilitate detection and quantification of the target biomarker. One of ordinary skill in the art would have a reasonable expectation of success in making this modification because both Nawana and the reference claims are directed to similar graphene sensors comprising electrically conductive pads coupled to an antibody functionalized graphene layer for measuring an electrical property of the antibody functionalized graphene layer.
Nawana further teaches the sensor comprising an analyzer having a data acquisition unit configured to acquire said electrical data and an analysis module for processing the acquired electrical data to measure an electrical resistance of the graphene layer so as to quantify the target analyte in the blood at levels suitable for use of the analyte as an indicator of prostate cancer (Pg. 3, Par. 4: an analyzer can be coupled to the sensor for receiving data from the test sensing unit and the calibration sensing unit and operating on said data to quantify the amount of the biomarker in the biological sample; Pg. 12, last Par-Pg. 13, first Par.; Pg. 1, Par. 2: sample may be a blood sample, e.g. plasma sample; Pg. 17, Par. 2: a sensor according to the present teachings can detect any of the above analytes at a concentration as low as 1 pg/mL).
It would have been obvious to one of ordinary skill in the art to have modified the sensor taught by the reference claims to include the analyzer as taught by Nawana, because one would recognize that such an analyzer can facilitate acquisition and analysis of data from the sensor in order to determine presence and quantity of the target analyte in a sample. One of ordinary skill in the art would have a reasonable expectation of success in making this modification because both Nawana and the reference claims are directed to similar graphene sensors for the detection of a target analyte.
Nawana does not explicitly teach the sensor wherein the antibodies exhibit specific binding to a prostate specific biomarker, such as PSA, however Nawana does teach that the biomarker detected by the disclosed sensor may be a protein analyte which is not particularly limited (Pg. 7, Par. 4: analyte may comprise an allergen, protein, gluten protein, pathogen, bacteria, virus; Pg. 5-6).
Regarding instant claims 1-2, Li teaches an electrochemical immunosensor for the detection of PSA comprising a graphene layer disposed on a substrate, wherein the graphene layer is functionalized with anti-PSA antibodies and is coupled to a plurality of electrodes (Abstract: an electrochemical immunosensor for PSA detection using the amino-functionalized graphene sheet -ferrocenecarboxyaldehyde composite material (NH2-GS@FCA); Fig. 1 shows the graphene layer deposited on an electrode substrate and functionalized with antibody Ab1; Pg. 77, Col. 1, Par. 3: The antibody Ab1 may be anti-PSA antibody. Electrochemical measurements were made with a conventional three-electrode system employing a working electrode, reference electrode, and counter electrode).
It would have been obvious to one of ordinary skill in the art to have modified the sensor taught by the reference claims use anti-PSA antibodies for the detection of the prostate-specific biomarker PSA, as taught by Li, because one of ordinary skill in the art would use the appropriate antibody to detect the desired analyte, such as the anti-PSA antibody of Li for the detection of PSA. Additionally, one would have been motivated to modify the sensor for the detection of PSA because Li teaches that PSA is a biomarker that is known in the art to be clinically important for the detection and diagnosis of prostate cancer (Li, Abstract). One of ordinary skill in the art would have a reasonable expectation of success in making this modification because both the reference claims and Li disclose sensor devices comprising a graphene layer disposed on a substrate and functionalized with antibodies that specifically bind to a target analyte.
All additional limitations of instant claim 3 are taught by reference claim 25.
All additional limitations of instant claim 4 are taught by reference claim 30.
All additional limitations of rinstant claim 5 are taught by reference claim 32.
All additional limitations of instant claim 6 are taught by reference claim 33.
Regarding instant claims 8-9, reference claim 25 teaches that the graphene layer is disposed on a substrate, but does not explicitly teach that the substrate comprises a semiconductor such as slilicon.
Regarding instant claims 8-9 Nawana teaches that the graphene layer is disposed on a substrate wherein the substrate may comprise a semiconductor such as silicon (Pg. 4, Par. 4).
It would have been obvious to one of ordinary skill in the art to modify the sensor of the reference claim such that the substrate comprises silicon, as taught by Nawana. One would be motivated to make this modification because one would be motivated to use an appropriate material for the substrate of the disclosed sensor, and Nawana teaches that silicon is an appropriate substrate material. One of ordinary skill in the art would have a reasonable expectation of success in making this modification because both the reference claims and Nawana are directed to similar sensors comprising an antibody functionalized graphene layer disposed on a substrate.
Regarding instant claims 18 and 20-21 the reference claims do not teach the sensor further comprising a calibration sensing element.
Nawana teaches the sensor further comprising a calibration sensing element comprising a graphene layer deposited on an underlying substrate, and a plurality of antibodies coupled to the graphene layer, wherein the antibodies exhibit specific binding to the target analyte (Pg. 3, Par. 2).
It would have been obvious to one of ordinary skill in the art to modify the sensor of the reference claims to further include a calibration sensing element such as the one taught by Nawana because Nawana teaches that such as a calibration sensing element is beneficial in facilitating the detection and quantification of the target analyte. One of ordinary skill in the art would have a reasonable expectation of success in making this modification because both Nawana and the reference claims are directed to similar sensors comprising antibody functionalized graphene layers.
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
Applicant’s arguments filed 6 February 2025 have been fully considered.
Applicant’s arguments regarding 112(f) claim interpretation and associated 112(b) rejections are persuasive in view of the amendments to the claims, and the 112(f) interpretation and previous 112(b) rejections are withdrawn. New grounds of 112(b) rejection are presented above.
The 103 rejections of the previous office action are withdrawn as they no longer represent the closest prior art to the amended claims. New grounds of 103 rejection are presented above which address the amended features of the claims which were the basis of applicant’s arguments against the previous 103 rejection.
Conclusion
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/ELLIS FOLLETT LUSI/Examiner, Art Unit 1677
/CHRISTOPHER L CHIN/Primary Examiner, Art Unit 1677