DETAILED ACTION
Final Rejection
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 .
Claims Status
Claim 1 was amended. Claims 8 and 11-20 were cancelled. Claims 28-31 are newly added. Claims 1-7, 9, 10, and 21-31 are now pending.
Response to Arguments
The objection to claim 1 is withdrawn in view of the amendment to the claim.
Applicant’s arguments with respect to claim 1 have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Claim Rejections - 35 USC § 112
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 1-7, 9, 10, and 21-31 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 enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
Claim 1 recites that the lab-on-skin biosensor calibrates, during on body use of the bio-sensor, the measurement of the electrical property detected with the first electrode using the measurement of the vital sign detected with the second electrode.
Claim 28 recites the lab-on-skin biosensor is configured to record a first reading from a first electrode and record a second reading from a second electrode and calibrating the second reading using the first reading.
Claim 30 recites the lab-on-skin biosensor is configured to record a first reading from a resistive sensor and record a second reading from a chemical sensor and calibrating the second reading using the first reading.
A review of the citations to the specification provided by Applicants verifies written description support for the amended limitations ([0068] – “Resistive sensor readings using various systems and methods disclosed herein may also be used to calibrate chemical sensor readings during on-body use (e.g., frame 508)”). However, the Office could not locate how such a calibration of the first electrode (used to detect a measurement of an electrical property corresponding to a target molecule) or a chemical sensor is performed using a reading from a second electrode configured to detect a measurement of a physical property corresponding or resistive sensor. In determining whether a patent application meets the enablement requirement under 35 U.S.C. 112, several factors known as the Wands factors must be considered.
The first factor is the quantity of experimentation necessary. The specification notes that the second electrode or resistive sensor can be used to measure vital signs such as, “body temperature, respiration rate, heartrate, pupil dilation, etc.” ([0053]). The amount of experimentation required to assess which vital sign(s) could be used to calibrate the first electrode reading or chemical sensor reading would be significant and undue as to what aspect of calibration is required.
The next factor is the amount of direction or guidance presented. A search of the term “calibrat$” in the specification yields four hits. No other discussion of calibration that speaks to this limitation is noted in these hits.
The next factor is the presence or absence of working examples. No working examples were found in the disclosure as originally filed.
The next factor is the nature of the invention (i.e. what is the complexity of the invention and is it in a predictable or unpredictable field?). Lab-on-skin biosensing applications are complex as indicated by the tiny scale on which this invention operates. Add on the fact that this is dealing with measurement biological phenomena makes the degree of complexity and even greater and the predictability less.
The next factor is the state of the prior art which analyzes how well understood is the technology in the relevant field? In this case, lab-on-skin biosensors the Office does not believe that the state of the art is deep in regards to the use of a vital sign measurement for calibrating chemical electrode sensors.
The next factor to consider is the relative skill of those in the art. It is the Office’s opinion that a person of ordinary skill in the art would not be apprised of how all or even which subset of the vital signs noted in the specification can be used to calibrate a chemical.
The next factor is the predictability or unpredictability of the art. Biological measurement systems are not a predictable field to the degree necessary for someone in the art to easily ascertain what electrode-based vital sign measurement device can be used to calibrate a measurement device using a completely different mode of detection.
The final factor is the breadth of the claims. In this situation, the claim does not state how vital sign measurement is used to calibrate the first measurement. The amount of experimentation to arrive at how the calibration can occur would undoubtedly be undue for each factor described above.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1-3, 5-7, 9, 21, 22, 24, and 28-31 are rejected under 35 U.S.C. 103 as being unpatentable over Wang et al. (WO 2019/090161A1, previously cited) in view of Issadore et al. (US 20160271609) and Xu (WO2017/181027) and Lyster et al. (US 2003/0055478).
Regarding claim 1, Wang et al. disclose a lab-on-skin biosensor ([0010] – “device that merges lab-on-a-chip and electrochemical detection technologies”) comprising:
a microfluidics layer ([0007] the referenced microfluidic device coupled to one side of the first substrate includes channels for liquid movement; this would be layer 120 shown in Fig. 1B);
a moisture resistant layer (adhesion layer 130 has holes for permitting entry of sweat per [0048] and [0049], thus the structure of layer 130 is moisture resistant because only the engineered channels within 130 permit moisture entry);
a multimodal sensing layer comprising at least one electrode (see [0006] which discloses “a wearable electrochemical sensor device includes a first flexible substrate including an electrically insulating material; two or more electrodes disposed on the first flexible substrate”; multimodal was interpreted to mean more than one type of sensing, at [0010] it is disclosed that multiple electrodes may be included to sense more than one analyte of interest; layer 110 in Fig. 1B); and
a logic circuit comprising a processor and a non-transitory memory with computer executable instructions embedded thereon (see highlighted portions of [00118]);
wherein the microfluidics layer comprises multiple microchannels transversely oriented (interpreted as transverse to the first surface but could include other interpretations) to channel a biological sample from a first surface of the microfluidics layer to a second surface of the microfluidics layer, the biological sample comprising a target molecule (Fig. 1B shows channels 124 for moving sweat from the skin transversely from the side facing the skin to the opposite side of layer 120 and then laterally to a reservoir 123; other configurations are possible though);
the moisture resistant layer couples to the first surface of the microfluidics layer and comprises an aperture to enable the biological sample to enter the microchannels of the microfluidics layer (layer 130 is shown coupled to the first surface of layer 120 in Fig. 1B an includes openings for moving sweat from the skin to the device);
the multimodal sensing layer is fluidically coupled to the second surface of the microfluidics layer to receive the biological sample from the microchannels (layer 110 ‘s sensing structures are fluidically coupled to second surface of layer 120’s fluid channels for carrying sweat);
the logic circuit is electrically coupled to each electrode of the multimodal sensing layer ([00117] – “the electronics unit of the device 100 is electrically coupled to the two or more electrodes”; as noted in the previous section, [00143] states that the miniaturized circuity which includes the processor and memory, is configured to measure the sensor signal).
Wang et al. do not disclose that the microchannels in the microfluidics layer are laser engraved. Wang does disclose that the microfluidics layer (120) may be formed of PDMS or an elastomer. Issadore et al. teach a microfluidic apparatus for channeling fluids. Issadore et al. teach that the microfluidic device may be constructed of PDMS and that forming channels within the PDMS layer may be accomplished using laser-engraving ([0062]). It would have been obvious to a person having ordinary skill in the art at the time of the filing of the invention to further modify Wang et al. to use a laser-engraving process to form the channels because it is the use of a known technique to improve similar devices (methods or products) in the same way. The claim would have been obvious because the technique for improving a particular class of devices was part of the ordinary capabilities of a person of ordinary skill in the art, in view of the teaching of the technique for improvement in other situations. There would have been a reasonable expectation of success given that the laser engraving process in Issadore is performed on the same type of substrate found in Wang.
Wang’s electrode sensor differs in the manner of detection however. Wang do not disclose:
the multimodal sensing layer comprises a first electrode configured to detect a measurement of an electrical property corresponding to a target molecule being present in the biological sample;
the computer executable instructions, when executed by the processor, cause the lab-on-skin biosensor to: identify the electrical property detected with the first electrode when the target molecule is present in the biological sample; and
generate an indication identifying the presence of the target molecule based on the electrical property detected with the first electrode.
However, the Xu reference teaches a variety of sensing modalities including EIS (see discussion starting at [00071]). EIS measures the impedance between electrodes on the sensor. The electrodes are functionalized with detection molecules that analytes in the sample can bind to. The binding molecules causes a change in impedance between the electrodes and this change can be correlated to the amount of analyte present. Measurement data may be communicated to external devices [000104], [000108]). It would have been obvious to a person having ordinary skill in the art at the time of the filing of the invention to further modify Wang to include the sensing modality taught by Xu for measuring analytes because Xu teaches that this method is a highly sensitive technique.
Wang et al. do not disclose the multimodal sensing layer comprises a second electrode configured to detect a measurement of a vital sign of a user and the lab on skin biosensor configured to identify the vital sign detected with the second electrode upon a threshold vital sign measurement and generating an indication identifying the vital sign based on the measurement detected with the second electrode. However, Xu teaches an epidermal sensing system (Abstract). The sensing device for the skin includes an electrode layer ([00063]). The electrodes can be used to acquire an ECG signal from which heart rate may be derived ([000120] and [000127]). Xu also discloses that the device includes a temperature sensor array that can be used to measure skin temperature ([00074]) that is integrated with an electrochemical biomarker sensor ([00067]). Xu also discloses that data is communicated to an external health monitor for analysis, i.e. for viewing ([00010] and [000104]). It would have been obvious to a person having ordinary skill in the art at the time of the filing of the invention to further modify Wang et al. to include an electrode sensor as taught by Xu for measuring a vital sign such as ECG or temperature because Xu teaches that placement of such sensing features on a skin patch sensor can achieve intimate, conformal integration with tissues and organs with minimal mobility confinement.
Wang et al. also does not disclose that the biosensor can calibrate, during on-body use of the lab-on-skin biosensor, the measurement of the electrical property detected with the first electrode using the measurement of the vital sign detected with the second electrode (Wang does acknowledge that sensor response may require compensation for variations in temperatures (see [00107] last sentence). Lyster et al. teach a medical electrode for making complex impedance measurements ([0200] and abstract). Lyster et al. teach that the impedance measurement circuitry can include temperature measurement and compensation ([0200]). It would have been obvious to a person having ordinary skill in the art at the time of the filing of the invention to further modify Wang et al. to use the additional temperature sensor/electrode of Xu to compensate impedance measurements as taught by Lyster et al. because it ensures a more accurate measurement result. The limitation regarding performance during on-body use is an intended use limitation. The modification of Wang in view of Xu and Lyster et al. would be capable of performing this limitation.
Regarding claim 2, Wang et al. disclose wherein the multimodal sensing layer comprises polyimide film (see at least [0068] which discloses the construction of current collectors – i.e. electrodes – sandwiched between polyimide layers). Note, Xu also teaches that a layer of polyimide is used as a base layer upon which electrodes are deposited. (see at least [00095]).
Regarding claim 3, Xu teaches wherein the electrode comprises a catalytically active substrate (in the section discussing electrochemical biosensors starting at [00070], which includes the EIS sensing modality described above, Xu also teaches that enzyme tags can be added for detection via amperometric or potentiometric methods which employ electrodes; enzyme understood to be catalysts). It would have been obvious to a person having ordinary skill in the art at the time of the filing of the invention to further modify Wang et al. to include a catalytically active substrate such as the enzymes on the sensors taught by Xu because amounts to combining prior art elements according to known methods to yield predictable results. All the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would have yielded predictable results to one of ordinary skill in the art at the time of the invention.
Regarding claim 5, Xu teaches wherein the electrical property is an electrical current ([00070] reference to amperometric methods). The rationale for modifying remains the same.
Regarding claim 6, Xu teaches wherein the electrical property is an electrical voltage ([00070] reference to potentiometric methods). The rationale for modifying remains the same.
Regarding claim 7, Xu teaches that sensor may include electrochemical impedance spectroscopy techniques for detecting the presence analytes (see previous discussion of EIS methods at least [00071]). The rationale for modifying remains the same.
Regarding claim 9, Wang et al. disclose the lab-on-skin biosensor further comprising a display, wherein the computer executable instructions further cause the processor to output the indication identifying the presence of the target molecule to the display ([00118 – “The 1/0 of the data processing unit can also interface with other external interfaces, sources of data storage, and/or visual or audio display devices, etc. to retrieve and transfer data and information that can be processed by the processor, stored in the memory, or exhibited on an output unit or an external device. For example, in some embodiments, the platform can include a display unit configured to be in data communication with the data processing unit, e.g., via the 1/0, to provide a visual display, an audio display, and/or other sensory display”; also [00134] discloses that sodium and potassium data can be transferred to a laptop and displayed using a custom GUI).
Regarding claim 21, Xu teaches wherein a conductive substance is electrodeposited onto a surface of the first electrode (see at least [00095] where Sn is deposited onto Cu surfaces, but Xu also notes at [000102] that electrodeposition techniques are possible too). The rationale for modifying remains the same.
Regarding claim 22, Wang et al. do not disclose wherein the aperture is engraving onto a surface of the moisture resistant layer. The layer identified for the location of the aperture was layer 130 in the Wang reference which may also be formed with PDMS or elastomers. The Issadore reference teaches laser engraving PDMS to form microfluidics channel for forming droplets ([0062]) and thus modifying Wang to include laser engraving of the holes would have been obvious in view of Issadore et al. for the same reason in claim 1.
Regarding claim 24, Xu teaches wherein the target molecule comprises at least one of a group consisting of an electroactive molecule, non-electroactive molecule, protein, peptide, amino acid, antibody, vitamin, provitamin, drug metabolite, and hormone ([00052] discloses the detection of CRP, a protein as one example). The rationale for modifying remains the same.
Claim 28 is a substantially a subset of the limitations of claim 1 and is rejected in the same manner argued above.
Claim 29 is an intended use limitation. The modification of Wang in view of Xu and Lyster et al. would be capable of performing this limitation.
In claim 30, the second electrode is replaced by the narrower resistive sensor while the first electrode is replaced by the narrower chemical sensor. The remaining limitations of claim 30 are substantially a subset of the limitations of claim 1 and is rejected in the same manner argued above as the sensor in Xu and Lyster can are chemical sensors and resistive sensors.
Claim 31 is rejected using the same argument for claim 29.
Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Wang et al. in view of Issadore et al. and Xu and Lyster et al. as applied to claim 3 and further in view of GUY et al. (US2020/0008717A1, previously cited). Wang et al. do not disclose wherein the catalytically active substrate is graphene. However, Guy et al. teach devices for non-invasive transdermal extraction and detection of substances (see Abstract). Guy et al. teach a glucose sensor that uses platinum nanoparticles immobilized on graphene to form a detection electrode that produces a catalytic effect (see [0038]). It would have been obvious to a person having ordinary skill in the art at the time of the filing of the invention to further modify Wang et al. to use graphene as a catalytically active substance as taught by Guy et al. for measuring glucose because Guy et al. teach that it can boost the level of measurable current against background noise.
Claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over Wang et al. in view of Issadore et al. and Xu and Lyster et al. as applied to claim 1 and further in view of Faarbaek et al. (US 2008/0275327, previously cited). Wang et al. do not disclose wherein the moisture resistant layer comprises polyethylene terephthalate. However, Faarbaek et al. teach an adhesive device having microelectronic systems for monitoring physiological conditions that is attached to the skin ([0001]). Faarbaek teach that a cover layer may be integrated into an adhesive layer used to attach the device to the skin ([0025]). This cover layer provides additional protection from liquids ([0059]). The cover layer is preferably made of materials such as polyethylene terephthalate (PET) ([0112]). It would have been obvious to a person having ordinary skill in the art at the time of the filing of the invention to modify Wang et al. to use PET in the moisture resistant layer as taught by Faarbaek because it can help protect the electronics from moisture.
Claim 23 is rejected under 35 U.S.C. 103 as being unpatentable over Wang et al. in view of Issadore et al. and Xu and Lyster et al. as applied to claim 1 and further in view of Nayak et al. (US 20200150075, previously cited). Wang et al. do not disclose wherein the first electrode is laser scribed on a surface of the multimodal sensing layer. However, the technique of laser-scribing electrodes was known in the art. Nayak et al. teach, “Embodiments of the present disclosure provide a device including an on-chip electrode platform including one or more three-dimensional laser scribed graphene electrodes, methods of making the on-chip electrode platform, methods of analyzing (e.g., detecting, quantifying, and the like) chemicals and biochemicals, and the like” (see [0033], 3D laser scribing can therefore be implanted on a surface). It would have been obvious to a person having ordinary skill in the art at the time of the filing of the invention to further modify Wang et al. to laser scribe the electrodes on a surface as taught by Nayak et al. for forming the electrodes because it amounts to combining prior art elements according to known methods to yield predictable results. All the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would have yielded predictable results to one of ordinary skill in the art at the time of the invention. There would have been a reasonable expectation of success given the application to biochemical sensing in both references and the application.
Claims 25-27 are rejected under 35 U.S.C. 103 as being unpatentable over Wang et al. in view of Issadore et al. and Xu and Lyster et al. as applied to claim 1 and further in view of Rivello et al. (US 5403451, previously cited).
Regarding claim 25, Wang et al. do not disclose the lab-on-skin biosensor further comprising sweeping the electrode to regenerate the multimodal sensing layer in-situ. However, Rivello et al. teach the use of polymer electroactive electrodes for the detection of various molecules (col. 1, field of the invention and the first paragraph of the summary of the invention in col. 5, where the detection of target analytes or biological interactions such as antibody-antigen attachments are possible using these electrodes; see also col. 10, 3rd paragraph, see also example detection discussion in col. 4, 5th paragraph). Rivello teach that the detection electrode may be microsized (col. 9, last paragraph). Rivello teaches using sweeping and/or regeneration of the electrode (See col. 3, first paragraph reference to sweeping or col. 3, 6th paragraph reference to renewing the electrode). It would have been obvious to a person having ordinary skill in the art at the time of the filing of the invention to substitute the sensing modality disclosed in Wang with the Rivello’s biosensors because they can be renewed via the sweeping function.
Regarding claim 26, Wang et al. do not disclose wherein sweeping the first electrode enables continuous detection of the measurement of the electrical property corresponding to the target molecule. However, Rivello’s electrode functions this way as indicated at column 3, first paragraph where a voltage sweep is used to generate data. The rationale for modifying remains the same.
Regarding claim 27, Wang et al. do not disclose the limitations of claim 27. However, Rivello teaches wherein the electrode comprises a uniform redox probe (claim 2 reference to the electrode being oxidized and reduced), wherein the uniform redox probe is deposited on a surface of the electrode (see reference to deposition of the electrode in col. 10, first paragraph). The rationale for modifying is the same as in claim 25. Rivello does not expressly disclose whether the deposition is uniform. However, it would have been obvious to try by choosing from a finite number of predictable solutions (there are only two choices for deposition, uniform or not uniform). A person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense.
Conclusion
Claims 1-7, 9, 10, and 21-31 are rejected.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
/THO Q TRAN/Examiner, Art Unit 3791
/JACQUELINE CHENG/Supervisory Patent Examiner, Art Unit 3791