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
Claim 51 is objected to because of the following informalities:
“[…] said at least one electronic device comprises a plurality of potentiostat circuitries, said device comprising a plurality of measurement chambers […]”, should be “said electronic device” for clarity.
Appropriate correction is required.
Election/Restrictions
Applicant's election with traverse of the restriction requirement and electron of Group I, claims 49-55 and 68, drawn to a biosensor chip device, in the reply filed on 01/26/2026 is acknowledged. The traversal is on the grounds that Groups I-III are linked by a single general inventive concept and share the same corresponding special technical feature. This is not found persuasive because the restriction was found to have meet the requirements of 37 CFR 1.475 as the groups are found to have a common technical feature of electrodes, where at least one of said electrodes is a working electrode, said working electrode is connected directly or indirectly to at least one target binding site and/or moiety.
The requirement is still deemed proper and is therefore made FINAL.
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 51 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.
Regarding claim 51, it cites “The chip device of claim 49, wherein at least one of: (a) said at least one electronic device comprises a plurality of potentiostat circuitries […] (b) the plurality of electrodes comprises a plurality of working electrodes, at least one reference electrode, and at least one counter electrode, and wherein the device comprises a potentiostat circuitry and a multiplexer device […]” It is unclear what “the device” is referring to under section (b), as the claim cites both a chip device, and a electronic device prior to the limitation. This makes claim 51 indefinite as it does not clearly define what this device exactly is.
Claim 53 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.
Regarding claim 53, it is unclear if the antibody derivative, variant or biosimilar comprises just one of the amino acid sequences or multiple. Additionally, under MPEP 2115, the inclusion of sequences that comprise at least one antibody are considered to be material worked upon a device, and thus does not impart patentability to the claims (see MPEP 2115, Claim analysis is highly fact-dependent. A claim is only limited by positively recited elements. Thus, “[i]nclusion of the material or article worked upon by a structure being claimed does not impart patentability to the claims.” In re Otto, 312 F.2d 937, 136 USPQ 458, 459 (CCPA 1963); see also In re Young, 75 F.2d 996, 25 USPQ 69 (CCPA 1935)).
This makes claims 53 indefinite for not being clear what this antibody comprises, and for being merely materials worked upon within a device claim.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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 49 and 68 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Mannoor et al. ("Electrical detection of pathogenic bacteria via immobilized antimicrobial peptides", as cited in the IDS).
Regarding claim 49, Mannoor et al. teaches a biosensor chip device usable for identifying and/or quantifying a target in a sample by electrochemical impedance spectroscopy (EIS) analysis (see Abstract, pg. 19207-19208, disclosing the development of a robust and portable biosensor for the detection of pathogenic bacteria, utilizing impedance spectroscopy on a micro capacitive biosensor.), the chip device comprising: a plurality of electrodes connectable to at least one electronic device (see pg. 19208, label-free electronic biosensor based on the hybridization of the antimicrobial peptide magainin I with interdigitated microelectrode arrays.); wherein at least one of said electrodes is a working electrode, said working electrode is connected directly or indirectly to at least one target binding site and/or moiety, wherein said target binding site and/or moiety specifically binds said at least one target or any component thereof (see pg. 19208, micro capacitive sensor detects impedance changes in the dielectric properties of an electrode surface upon analyte binding, where the variation in the impedance is directly proportional to the activity of analyte binding.), and wherein said plurality of electrodes is configured for electrochemical impedance spectroscopy (EIS) analysis of said sample (see pg. 19208, disclosing label-free electronic biosensor based on the hybridization of the antimicrobial peptide magainin I with interdigitated microelectrode arrays for the sensitive and selective detection of pathogenic bacteria via impedance spectroscopy.).
Regarding claim 68, Mannoor et al. teaches at least one system comprising at least one biosensor chip device according to claim 49, usable for identifying and/or quantifying a target in a sample by electrochemical impedance spectroscopy (EIS) analysis (see Abstract, pg. 19207-19208, disclosing the the development of a robust and portable biosensor for the detection of pathogenic bacteria, utilizing impedance spectroscopy on a micro capacitive biosensor.), the chip device comprising: a plurality of electrodes connectable to at least one electronic device (see pg. 19208, label-free electronic biosensor based on the hybridization of the antimicrobial peptide magainin I with interdigitated microelectrode arrays.); wherein at least one of said electrodes is a working electrode, said working electrode is connected directly or indirectly to at least one target binding site and/or moiety, wherein said target binding site and/or moiety specifically binds said at least one target or any component thereof (see pg. 19208, micro capacitive sensor detects impedance changes in the dielectric properties of an electrode surface upon analyte binding, where the variation in the impedance is directly proportional to the activity of analyte binding.), and wherein said plurality of electrodes is configured for electrochemical impedance spectroscopy (EIS) analysis of said sample (see pg. 19208, disclosing label-free electronic biosensor based on the hybridization of the antimicrobial peptide magainin I with interdigitated microelectrode arrays for the sensitive and selective detection of pathogenic bacteria via impedance spectroscopy.).
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.
Claim 50 is rejected under 35 U.S.C. 103 as being unpatentable over Mannor et al. as applied to claim 49 above, and further in view of Yang et al. (US PG-Pub 20130332085 A1).
Regarding claim 50, Mannoor et al. teaches interdigitated capacitive electrodes microfabricated on a 4" p-type silicon wafers. A 1-μm thick silicon dioxide layer was deposited on the wafer by plasma enhanced chemical vapor deposition to form electrical insulation between the Si substrate and the capacitive electrodes. A polydimethylsiloxane (PDMS) microfluidic flow cell consisting of a detection microchamber with an embedded microelectrode array and inlet and outlet ports was formed by bonding the IMA chip to the PDMS channel. The PDMS microchannel formed on the master mold was partially cured, aligned with the microelectrode array, and bonded by permanently curing at 80ºC for 2–3 h. Microfluidic connectors were fixed onto the inlet and outlet ports through drilled holes (see Mannoor et al., pg. 19211, Interdigitated Microelectrode Array (IMA) and Microfluidic Flow Cell). Mannoor et al. additionally teaches a micro capacitive sensor that detects impedance changes in the dielectric properties of an electrode surface upon analyte binding, where the variation in the impedance is directly proportional to the activity of analyte binding (see Mannoor et al., pg. 19208).
Mannoor et al. fails to teach the plurality of electrodes comprising at least one counter electrode configured to introduce electrical currents into said measurement chamber, and at least one reference electrode for measuring electrical voltage between said at least one working electrode and said at least one reference electrode.
However, in the analogous art of applications of electrochemical impedance spectroscopy in sensor systems, Yang et al. teaches a sensor system includes a subcutaneous or implanted sensor having a plurality of independent working electrodes, a counter electrode, and a reference electrode, and sensor electronics operably coupled to the sensor. The sensor electronics, in turn, include electronic circuitry configured to selectively perform an electrochemical impedance spectroscopy (EIS) procedure for one or more of the pluralities of independent working electrodes to generate impedance-related data for the one or more working electrodes (see Yang et al., [0023]). In a long-term sensor embodiment, where a glucose oxidase (GOx) enzyme is used as a catalytic agent in a sensor, current may flow from the counter electrode 536 to a working electrode 534 only if there is oxygen in the vicinity of the enzyme and the sensor electrodes 510 (see Yang et al., Fig. 5, [0116]). For sensor and sensor electronics utilizing an analyzation module for feedback in a stabilization period, Fig. 9B illustrates an analyzation module 950 that may measure a voltage, a current, a resistance, or an impedance in the sensor 355. The measurement occurs at the working electrode 375, but this should not limit the invention because other embodiments of the invention may measure a voltage, a current, a resistance, or an impedance in between electrodes of the sensor or directly at either the reference electrode 370 or the counter electrode 365 (see Yang et al., Fig 9B, [0149]).
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 fabrication of the electrodes, microchamber, and microfluidic cell of Mannoor et al. to incorporate electrodes comprising counter electrode that provides current and a reference electrode that measures voltage between it and a working electrode (as taught by Yang et al.), for the benefit of adding electrode redundancy as to improve the overall reliability of the sensor, and the frequency of the need, if at all, for calibration reference values (see Yang et al., [0011]).
Claim 51 is rejected under 35 U.S.C. 103 as being unpatentable over Mannoor et al. as applied to claim 49 above, and further in view of Terbrueggen et al. (US PG-Pub 20040053290 A1) and Yang et al.
Regarding claim 51, the examiner is interpreting “the device” on line 10 of claim 51 to be an electronic device.
Mannoor teaches a polydimethylsiloxane (PDMS) microfluidic flow cell consisting of a detection microchamber with an embedded microelectrode array and inlet and outlet ports was formed by bonding the IMA chip to the PDMS channel (see Mannoor et al., pg. 19211, Interdigitated Microelectrode Array (IMA) and Microfluidic Flow Cell).
Mannoor et al. fails to teach wherein at least one of: (a) said at least one electronic device comprises a plurality of potentiostat circuitries, said device comprising a plurality of measurement chambers, each comprising at least three of the plurality of electrodes defining a working electrode, a reference electrode, and a counter electrode, and a respective plurality of potentiostat circuitries each of which are electrically connected to the at least three electrodes of its respective measurement chamber; and (b) the plurality of electrodes comprises a plurality of working electrodes, at least one reference electrode, and at least one counter electrode, and wherein the device comprises a potentiostat circuitry and a multiplexer device configured to selective transfer signals measured by said plurality of working electrodes to said potentiostat circuitry.
However, in the analogous art of devices and methods for biochip multiplexing, Terbrueggen et al. teaches biochip cartridges comprising one or more reaction chambers, configured to include inlet and outlet ports, as well as a detection chamber with an array of electrodes. The invention provides methods and compositions for the multiplex analysis of samples and target analytes. A potential is applied to the assay complex. Precise control and variations in the applied potential can be via a potentiostat and either a three electrode system (one reference, one sample (or working) and one counter electrode) or a two electrode system (one sample and one counter electrode) (see Terbrueggen et al., [0008]-[0009], [0461]).
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 microchamber of Mannoor et al. to incorporate more than one chamber, and the set of three electrodes under a potentiostat (as taught by Terbrueggen et al.), for the benefit of simultaneous biochip analysis for high throughput analysis of samples (see Terbrueggen et al., Abstract).
Futhermore, the combination of Mannoor et al. and Terbrueggen et al. al. fails to teach electronic device comprising a plurality of potentiostat circuitries and a multiplexer device configured to selective transfer signals measured by said plurality of working electrodes to said potentiostat circuitry.
However, Yang et al. teaches an Application Specific Integrated Circuit (ASIC) enables implementation of the EIS-based diagnostics, fusion algorithms, and other processes based on measurement of EIS-based parameters. Embodiments of the invention are also directed to an Analog Front End Integrated Circuit (AFE IC), which is a custom Application Specific Integrated Circuit (ASIC) that provides the necessary analog electronics to: (i) support multiple potentiostats and interface with multi-terminal glucose sensors based on either Oxygen or Peroxide; (ii) interface with a microcontroller so as to form a micropower sensor system; and (iii) implement EIS diagnostics, fusion algorithms, and other EIS-based processes based on measurement of EIS-based parameters (see Yang et al., Abstract, [0291]). The sensor circuitry supports up to five sensor work electrodes 4310 with additional embodiments accommodating a larger number of electrodes. While the peroxide sensor work electrodes source current, the oxygen sensor work electrodes sink current. These sensors can be configured in the potentiostat configuration. The interface electronics include a multiplexer 4250 so that the counter and reference electrodes may be connected to any of the (redundant) work electrodes (see Yang et al., [0339]-[0340]).
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 plurality of detection chamber and the set of three electrodes under a potentiostat of Mannoor et al. and Terbrueggen et al. to further incorporate multiple potentiostats, electronically connected to working sensor electrodes and a multiplexer (as taught by Yang et al.), for the benefit of adding electrode redundancy as to improve the overall reliability of the sensor, and the frequency of the need, if at all, for calibration reference values (see Yang et al., [0011]).
Claims 52-54 are rejected under 35 U.S.C. 103 as being unpatentable over Mannoor et al. as applied to claim 49 above, and further in view of Hillman et al. ("An anti-bacterial monoclonal antibody that targets pathogenic bacteria expressing the type 3 secretion system for therapeutic and diagnostic applications", as cited in the IDS).
Regarding claim 52, Mannoor et al. teaches immobilizing semi-selective antimicrobial peptide magainin I on gold microelectrodes via a C-terminal cysteine residue, where a micro capacitive sensor detects impedance changes in the dielectric properties of an electrode surface upon analyte binding (see Mannoor et al., Abstract, 19207-19208).
Mannoor et al. fails to teach wherein at least one of: (a) said target is at least one pathogen expressing at least one component of the Type III Secretion System (T3SS); (b) said at least one target binding site and/or moiety is comprised within at least one antibody that recognizes and binds at least one component of the T3SS, or any combination or complex thereof, said antibody or any functional fragments thereof is immobilized to said at least one working electrodes; (c) said component of said T3SS is at least one of the Enteropathogenic Escherichia coli (EPEC) secreted protein A (EspA), EPEC secreted protein B (EspB), and EPEC secreted protein D (EspD), or any fragments or peptides thereof, and any combination or complex thereof; and (d) wherein said at least one antibody recognizes and binds the EspB protein, or any complex thereof with EspD protein.
However, in the analogous art of anti-bacterial monoclonal antibody that targets pathogenic bacteria expressing the type 3 secretion system for therapeutic and diagnostic applications, Hillman et al. teaches the development of a novel monoclonal antibody, known as mAb-EspB-B7, that targets EspB, a component within the bacterial type 3 secretion system (T3SS), which is mainly expressed in Gram-negative pathogens and is essential for bacterial infectivity. It was found that mAb-EspB-B7 has high affinity and specificity towards recombinant and native EspB proteins, is stable over a range of pH levels, temperatures and salt concentrations, and retains its functionality in human serum (see Hillman et al., Abstract).
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 immobilizing a target analyte on an electrode from Mannoor et al. to incorporate the target being a component within T3SS such as EspB proteins, binding with the MAb-EspB-B7 monoclonal antibody (as taught by Hillman et al.), for the benefit of being able to effectively control the antibiotic resistance bacteria and provide rapid and accurate surveillance and diagnosis of these multiple-drug resistant bacterial strains (see Hillman et al., pg. 2, Introduction).
Regarding claim 53, Mannoor et al fails to teach The chip device of claim 52, wherein said at least one antibody recognizes and binds the EspB protein, said antibody comprises a heavy chain complementarity determining region (CDRH) 1 comprising the amino acid sequence GFTFSHYA, as denoted by SEQ ID NO. 6, CDRH2 comprising the amino acid sequence INSNGDST, as denoted by SEQ ID NO. 10, CDRH3 comprising the amino acid sequence ARDRRAGYFDYW, as denoted by SEQ ID NO. 14, and a light chain complementarity determining region (CDRL) 1 comprising the amino acid sequence RDNIGKNY as denoted by SEQ ID NO. 22, a CDRL2 comprising the amino acid sequence RNN as denoted by SEQ ID NO. 26, and a CDRL3 comprising the amino acid sequence SAWDTSLNA as denoted by SEQ ID NO. 30, or any derivative, variant and biosimilar thereof.
However, Hillman et al. teaches the antibody mAb-EspB-B7, which is found to have a high affinity and specificity towards recombinant and native EspB proteins. Following Figure 6B of the amino acid sequence alignment of EspB from EPEC with C. rodentium, EHEC, orSalmonella EspB homologs, epitopes of mAb-EspB-B7 were found to match with the EspB sequences (see Hillman et al., Fig. 6, Abstract, mAb-EspB-B7 binds EspB homologs in other T3SS-expressing bacteria).
Under MPEP 2115, the inclusion of sequences that comprise at least one antibody are considered to be material worked upon a device, and thus does not impart patentability to the claims (see MPEP 2115, Claim analysis is highly fact-dependent. A claim is only limited by positively recited elements. Thus, “[i]nclusion of the material or article worked upon by a structure being claimed does not impart patentability to the claims.” In re Otto, 312 F.2d 937, 136 USPQ 458, 459 (CCPA 1963); see also In re Young, 75 F.2d 996, 25 USPQ 69 (CCPA 1935)).
Therefore, 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 electrochemical impedance spectroscopy analysis performed by Mannoor et al. to incorporate mAb-EspB-B7 as the binding antibody (as taught by Hillman et al. and which could be a biosimilar or variant of the claimed amino acid), for the benefit of providing a different specific binding reaction between the binding antibody and the protein.
Regarding claim 54, Mannoor et al. fails to teach wherein at least one of: (a) said pathogen is a bacterial pathogen, said bacteria is at least one Multiple Drug Resistant (MDR) bacteria, optionally, said MDR bacteria is at least one of Enteropathogenic Escherichia coli (EPEC) and Enterohemorrhagic Escherichia coli (EHEC); and (b) said sample is a biological sample or an environmental sample.
However, Hillman et al. teaches characterizing mAb-EspB-B7 in a novel application against the Type III Secretion System (T3SS) of enteropathogenic E. Coli (EPEC), which is a multiple drug-resistant pathogen (see Hillman et al., pg. 2-3, Introduction). Additionally, ELISA assays, with 96-well ELISA plates coated with purified EspB, were used to assess Mab-EspB-B7 binding to various conditions of serum, where the antibody was incubated in goat, horse, and human serum (see Hillman et al., pg. 3-4, 2.4 Enzyme-linked immunosorbent assay).
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 electrochemical impedance spectroscopy analysis performed by Mannoor et al. to incorporate the pathogen being enteropathogenic E. Coli and the sample being serum (as taught by Hillman et al.), for the benefit of being able to effectively control the antibiotic resistance bacteria (like EPEC) and provide rapid and accurate surveillance and diagnosis of these multiple-drug resistant bacterial strains (see Hillman et al., pg. 2, Introduction).
Claim 55 is rejected under 35 U.S.C. 103 as being unpatentable over Mannoor et al. as applied to claim 49 above, and further in view of Das et al. (US PG-Pub 20140005068 A1).
Regarding claim 55, Mannoor et al. teaches the development of a robust and portable biosensor for the detection of pathogenic bacteria, utilizing impedance spectroscopy on a micro capacitive biosensor, based on the hybridization of the antimicrobial peptide magainin I with interdigitated microelectrode arrays. Micro capacitive sensor detects impedance changes in the dielectric properties of an electrode surface upon analyte binding, where the variation in the impedance is directly proportional to the activity of analyte binding (see Mannoor et al., Abstract, pg. 19207-19208).
Mannoor et al. fails to teach where the biosensor chip device is a part of a kit and optionally, said kit comprises at least one of:(b) at least one control sample and/or control standard value; and (c) instructions for use.
However, in the analogous art of protein detection method, Das et al. teaches detection systems of electrochemically detecting a protein analyte, comprising an electrode which further contains a linker on its surface, wherein the linker is attached to an antibody or fragment thereof capable of binding a protein analyte. This electrode can be provided on a microfabricated chip. Further, Das et al. additionally teaches a kit comprising components for the described systems and for performing the described methods of the invention. The kit may include one or more components, including an electrode, reagents to form a linker on the surface of the electrode, one or more antibodies and a redox reporter. The components of a kit can be retained by a housing. Instructions for using the kit to perform a described method can be provided with the housing, and can be provided in any fixed medium. A kit may be in multiplex form for detection of one or more different target analytes (see Das et al., [0004], [0016], [0019], [0078]).
While Das et al. doesn't explicitly teaches the kit containing at least one control sample and/or control standard value, Das et al. does teach using a positive control sample known to contain a target analyte as well as a negative control sample that is not expected to contain the analyte, though is suspected via contamination or other components capable of producing a false positive (see Das et al., [0074]). 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 kit of Das et al. to include a control sample, for the benefit of determining whether a given set of assay conditions would produce false positives (see Das et al., [0074]). It also would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the biosensor of Mannoor et al. to further incorporate it as a kit (as taught by Das et al.), for the benefit of developing a cost effective and robust analysis system for clinical use (see Das et al., [0003]).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Tracy C Colena whose telephone number is (571)272-1625. The examiner can normally be reached Mon-Thus 8:00am-5:00pm.
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/TRACY CHING-TIAN COLENA/ Examiner, Art Unit 1797
/JENNIFER WECKER/ Primary Examiner, Art Unit 1797