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 Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Micro (US 2015/0208985, hereinafter MNT).
Regarding Claim 1, MNT discloses a device (abstract) comprising an aptamer microneedle patch ("AMPatch") (Para. 0038: The transdermal microneedle array patch of the present invention uses the flexible pad 30 to have tight fit with the user's muscle during operation thereof; Para. 0040: the first microneedle set 22 may be subjected to surface modification, in view of the target molecule to be sensed. Specifically, a molecule selected from the group consisting of...an aptamer...may be coated on the surface of the microneedles) configured to provide wearable therapeutic drug monitoring (TDM) (Para. 0038: The transdermal microneedle array patch of the present invention uses the flexible pad 30 to have tight fit with the user's muscle (wearable] during operation thereof; Para. 0039: The first microneedle set 22 of the working electrode of the transdermal microneedle array patch according to the invention may be subjected to surface modification, in view of the target molecule to be sensed...The transdermal microneedle array patch of the present invention may be used for pharmaceutical monitoring during the administration of a medication for a chronic disease or a specific pharmaceutical).
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.
Claim(s) 2-4 is/are rejected under 35 U.S.C. 103 as being unpatentable over Micro (US 2015/0208985, hereinafter MNT) in view of Hangzhou (CN 113406169, hereinafter Hangzhou).
Regarding Claim 2, MNT discloses the device of claim 1, wherein the AMPatch includes a gold coating on a needle (Para. 0040: the first microneedle set 22 may be subjected to surface modification, in view of the target molecule to be sensed...For coupling of an antibody or an aptamer, self-assembled monolayer (SAM) may be applied to the microneedle deposited with gold).
MNT fails to explicitly disclose a gold nanoparticle (AuNP) coating on a clinically-validated needle.
Hangzhou is in the field of electrochemical sensors (abstract) and teaches gold nanoparticle (AuNP) coating on a clinically-validated needle (Para. 0052: the acupuncture needle [clinically-validated needle] electrode with the needle point covered with the gold nanoparticles is obtained).
It would have been obvious to one of ordinary skill in the art at the time of the invention to modify the device of MNT to include a needle as taught by Hangzhou for the purpose of providing low priced needles with simple and convenient operation aspects and is widely applied in the medical field (Hangzhou, Para. 0005).
Regarding Claim 3, modified MNT discloses the device of claim 2, wherein the gold coating configures the needle into a high-quality gold working electrode substrate (Para. 0027: a first microneedle set 22 used as a working electrode; Para. 0040: the microneedle deposited with gold) for strong and compact aptamer immobilization (Para. 0040: the first microneedle set 22 may be subjected to surface modification, in view of the target molecule to be sensed...For coupling of an antibody or an aptamer [aptamer immobilization onto surface of microneedles], self-assembled monolayer (SAM) may be applied to the microneedle deposited with gold, before adding the antibody or the aptamer. Next, in order to ensure the specificity, a blocking molecule is applied to the position that the antibody or the aptamer fails to be coupled on SAM [improving the coupling/immobilization of aptamers onto the gold microneedles]; see further Applicant's Para. 0021 for definition of aptamer immobilization).
MNT fails to explicitly disclose the gold nanoparticle coating.
Hangzhou teaches the gold nanoparticle coating (Para. 0022: The invention also aims to provide an acupuncture needle imprinting electrochemical sensor for detecting dopamine, which comprises a working electrode...wherein a substrate electrode of the working electrode is a stainless steel acupuncture needle electrode, a layer of gold nano material is modified on the surface of the stainless steel acupuncture needle electrode).
It would have been obvious to one of ordinary skill in the art at the time of the invention to modify the device of MNT to include gold nanoparticles as taught by Hangzhou for the purpose of providing materials and structures for sensing a target molecule with a quick response, strong anti-interference capability, high sensitivity, and good stability (Hangzhou, abstract).
Regarding Claim 4, MNT discloses the device of any of claims 1-3, further comprising sensing interfaces built on the tip of shortened gold 'needles (Para. 0040: For specificity, the first microneedle set 22 [shortened needles] may be subjected to surface modification, in view of the target molecule to be sensed [sensing interfaces]...For coupling of an antibody or an aptamer [sensing interfaces], self-assembled monolayer (SAM) may be applied to the microneedle deposited with gold; Para. 0042: a biotinylated ssDNA aptamer [sensing interfaces] on a surface of the microneedle of streptavidin-modified electrode is suitable to measure the concentration of tetracycline, wherein the biotinylated ssDNA aptamer has specificity to tetracycline).
MNT fails to explicitly disclose acupuncture needles.
Hangzhou teaches an acupuncture needle (Para. 0022: The invention also aims to provide an acupuncture needle imprinting electrochemical sensor for detecting dopamine).
Therefore, it would have been ii would have been obvious to one of ordinary skill in the art at the time the invention was made to teach acupuncture needles, since a mere duplication of essential working parts of a device involves only routine skill in the art. The motivation for doing so would have been to provide low priced needles with simple and convenient operation aspects and is widely applied in the medical field (Hangzhou, Para. 0005).
Claim(s) 5-6 is/are rejected under 35 U.S.C. 103 as being unpatentable over Commonwealth Scientific and Industrial Research (WO 2021/232109) in view of Hangzhou (CN 113406169).
Regarding Claim 5, Commonwealth discloses a simple and low-cost EAB-on-microneedle method of fabricating an aptamer microneedle patch (AMPatch) (Pg. 3 lines 27 - 37: Desirably, the electrode and connector support is formed from a metal such as gold or silicon or in some embodiments may be a 3D printed support, for example, formed from a photocurable polymer such as OrmoComp®. In embodiments utilising a sputtered gold conducting nanofilm, a 3D printed support is preferred for reduced cost reasons as 3D printed materials are inexpensive and support bulk manufacturing [simple, low-cost fabrication]; Pg. 5 lines 7 - 1O: surfaces of nanofilm of the working electrode are modified with biorecognition elements which are selective for a bioanalyte of interest. Preferred biorecognition elements include one or more of...aptamers; Pg. 12 lines 34 - 36: a working (WE) electrode comprising a working electrode substrate supporting an array of electrically conductive biocompatible microneedles at a density of at least 2,000 microneedle/cm2 disposed on the working electrode substrate [microneedle patch]) for in-situ ISF biomonitoring (Pg. 14 lines 10 - 21: the sensor is adapted for continuous 'monitoring sensing of in vivo pH or bioanalyte monitoring, preferably continuous in vivo pH or bioanalyte monitoring
of interstitial fluid residing in the skin, that is the dermis and epidermis), comprising: engineering a gold nanoparticle (AuNP) coating via a single deposition step (Pg. 17 line 37 - Pg. 18 line 30: at least the microneedles of one or more of the reference electrode substrate, the counter electrode substrate and working electrode substrate are coated with or otherwise provided with at least one thin film of an electrically conductive but chemically inert material, preferably a conformal film, more preferably a conformal nanofilm...the entirety of each electrode that is microneedles and substrate base is coated with the at least one film of the material...the biocompatible material is preferably a gold or platinum conformal nanofilm most preferably electro-sputtered gold [deposition step; sputtering is well known to bombard particles onto a substrate for deposition, in this case gold nanoparticles] or platinum), which uniquely transforms a needle into a high-quality gold working electrode substrate (Pg. 17 line 37 - Pg. 18 line 30: at least the microneedles of one or more of the reference electrode substrate, the counter electrode substrate and working electrode substrate are coated with or otherwise provided with at least one thin film of an electrically conductive but chemically inert material, preferably a conformal film, more preferably a conformal nanofilm...the biocompatible material is preferably a gold or platinum conformal nanofilm) for strong and compact aptamer immobilization (Pg. 4 lines 16 - 27: the electrode surface is a conformal gold or platinum nanofilm; Pg. 5 lines 8 - 10: Desirably, surfaces of nanofilm of the working electrode are modified with biorecognition elements which are selective for a bioanalyte of interest. Preferred biorecognition elements include one or more of...aptamers).
Commonwealth fails to explicitly teach a clinically-validated needle.
Hangzhou teaches a clinically-validated needle (Para. 0052: the acupuncture needle (clinically-validated needle] electrode with the needle point covered with the gold nanoparticles is obtained).
It would have been obvious to one of ordinary skill in the art at the time of the invention to modify the device of Commonwealth to include a needle as taught by Hangzhou for the purpose of providing low priced needles with simple and convenient operation aspects and is widely applied in the medical field (Hangzhou, Para. 0005).
Regarding Claim 6, modified Commonwealth discloses the method of claim 5, wherein sensing interfaces are built on the tip of shortened
I gold needles (Para. 0023: the electrode surface is a conformal gold or platinum nanofilm; Para. 0025: the working electrode are modified
i with biorecognition elements [sensing interfaces] which are selective for a bioanalyte of interest. Preferred biorecognition elements include 'one or more of enzymes, antibodies, antigens, and aptamers; Para. 0107: at least the microneedles of one or more of the reference electrode substrate, the counter electrode substrate and working electrode substrate are coated with or otherwise provided with at least one thin film of an electrically conductive but chemically inert material, preferably a conformal film, more preferably a conformal nanofilm...the entirety of each electrode that is microneedles [shortened needles] and substrate base is coated with the at least one film of the material...the biocompatible material is preferably a gold or platinum conformal nanofilm), allowing to simultaneously leverage the needles' high sharpness for skin penetration and conductivity for signal routing (Paras. 0092-0094: the sensor is adapted for continuous monitoring sensing of in vivo pH or bioanalyte monitoring, preferably continuous in vivo pH or bioanalyte monitoring
of interstitial fluid residing in the skin, that is the dermis and epidermis. Desirably sensors may be used repeatedly, that is inserted into skin...the inventors have found a very high microneedle array skin pierceable MNA provided with a nanolayer or a nanofilm of a chemically inert but electrically conductive material as described for pH or bioanalyte sensing using a suitably robust sensing bioreceptor which facilitates continuous and stable bioreceptor activity upon interacting with a bioanalyte directly in interstitial fluid in a manner that involves continuous interfacing, monitoring and sensing [sensing signals while piercing skin]...The electrochemical sensor system involves an electrochemical cell whose output signal is directly related to the concentration of the bioanalyte species in the medium of interest [signal routing]).
Commonwealth fails to explicitly disclose acupuncture needles.
Hangzhou teaches acupuncture needles (Para. 0022: The invention also aims to provide an acupuncture needle imprinting electrochemical sensor for detecting dopamine).
Therefore, it would have been it would have been obvious to one of ordinary skill in the art at the time the invention was made to teach acupuncture needles, since a mere duplication of essential working parts of a device involves only routine skill in the art. The motivation for doing so would have been to provide low priced needles with simple and convenient operation aspects and is widely applied in the medical field (Hangzhou, Para. 0005).
Claim(s) 7, 11-12 is/are rejected under 35 U.S.C. 103 as being unpatentable over Micro (US 2015/0208985, hereinafter MNT) in view of Glauser (US 2008/0171697).
Regarding Claim 7, MNT discloses a method using minimally-invasive wearable technology (Para. 0006: Transdermal sensor with
i array-arranged microneedles pricking through skin is developed to withdraw tissue fluid in painless and minimally-invasive way; Para. 0009: One object of the present invention is to provide a transdermal microneedle array patch), comprising: longitudinally tracking a drug included in one of various classes of circulating pharmaceuticals in real-time using an aptamer microneedle patch (AMPatch) (Paras.
0039-0042: The first microneedle set 22 of the working electrode of the transdermal microneedle array patch according to the invention may be subjected to surface modification, in view of the target molecule to be sensed...The transdermal microneedle array patch of the present invention may be used for pharmaceutical monitoring during the administration of a medication for a chronic disease or a specific pharmaceutical...the first microneedle set 22 may be subjected to surface modification, in view of the target molecule to be sensed.
Specifically, a molecule selected from the group consisting of...an aptamer...may be coated on the surface of the microneedles ...For tracing the changes in concentration of tetracycline over time in a patient's body [real-time tracking], a transdermal microneedle array patch coupling a biotinylated ssDNA aptamer on a surface of the microneedle of streptavidin-modified electrode is suitable to measure the concentration of tetracycline [a drug included in one of various classes of circulating pharmaceuticals]), thereby improving pharmacotherapy outcomes by guiding clinical decisions and facilitating timely interventions (Para. 0042: Therefore, the transdermal microneedle array patch of the present invention may be used for pharmaceutical monitoring during the administration of a medication for chronic disease or a specific pharmaceutical. Personalized medication of a specific dosage or frequency of administration can be provided base).
MNT fails to explicitly disclose tracking pharmacokinetic (PK) profiles of a drug.
Glauser is in the field of generating a dosage regimen recommendation for individual patients (title; abstract) and teaches tracking pharmacokinetic (PK) profiles of a drug (Para. 0023: FIG. 2 presents risperidone pharmacokinetic profiles for three different dosing regimens for a particular patient....ln each panel a solid line indicates the patient's compound concentration predicted by the methods of the invention in each dosing regimen and the broken line indicates the therapeutic range, in this example arbitrarily chosen to be between 3 and 1Ong/ml. The observed biomarker value is indicated with solid circles or triangles).
It would have been obvious to one of ordinary skill in the art at the time of the invention to modify the method of MNT to include tracking pharmacokinetic (PK) profiles of a drug as taught by Glauser for the purpose of providing a method of defining and describing the relationships between drug action and patient variability.
With respect 11, Glauser discloses further comprising providing generalizable wearable pharmaceutical sensing interfaces with built-in signal enhancement features (see para. 0021).
With respect to claim 12, Glauser discloses further comprising providing a scalable analytical framework to infer the circulating target's pharmacokinetic profile based on ISF readings (see para. 0136-0140).
Claim(s) 8-10 is/are rejected under 35 U.S.C. 103 as being unpatentable over Micro (US 2015/0208985, hereinafter MNT) in view of Glauser (US 2008/0171697), as applied to claim 7, in further view of Hangzhou (CN 113406169).
Regarding Claim 8, modified MNT discloses the method of claim 7, wherein the AMPatch includes a gold coating on a needle (Para. 0040: (Para. 0040: the first microneedle set 22 may be subjected to surface modification, in view of the target molecule to be sensed...For coupling of an antibody or an aptamer, self-assembled monolayer (SAM) may be applied to the microneedle deposited with gold).
MNT fails to explicitly disclose a gold nanoparticle (AuNP) coating on a clinically-validated needle.
Hangzhou teaches a gold nanoparticle (AuNP) coating on a clinically-validated needle (Para. 0052: the acupuncture needle [clinically-validated needle] electrode with the needle point covered with the gold nanoparticles is obtained).
It would have been obvious to one of ordinary skill in the art at the time of the invention to modify the method of MNT to include a needle as taught by Hangzhou for the purpose of providing low priced needles with simple and convenient operation aspects and is widely applied in the medical field (Hangzhou, Para. 0005).
I Regarding Claim 9, modified MNT discloses the method of claim 8, wherein the gold coating configures the needle into a high-quality gold working electrode substrate (Para. 0027: a first microneedle set 22 used as a working electrode; Para. 0040: the microneedle deposited with gold) for strong and compact aptamer immobilization (Para. 0040: the first microneedle set 22 may be subjected lo surface modification, in view of the target molecule lo be sensed...For coupling of an antibody or an aptamer [aplamer immobilization onto surface of microneedles], self-assembled monolayer (SAM) may be applied lo the microneedle deposited with gold, before adding the antibody or the aplamer. Next, in order to ensure the specificity, a blocking molecule is applied to the position that the antibody or the aptamer fails to be coupled on SAM [improving the coupling/immobilization of aptamers onto the gold microneedles]; see further Applicant's Para. 0021 for definition of aplamer immobilization).
MNT fails to explicitly disclose the gold nanoparticle coaling.
Hangzhou teaches the gold nanoparticle coaling (Para. 0022: The invention also aims lo provide an acupuncture needle imprinting electrochemical sensor for detecting dopamine, which comprises a working eleclrode...wherein a substrate electrode of the working electrode is a stainless steel acupuncture needle electrode, a layer of gold nano material is modified on the surface of the stainless steel acupuncture needle electrode).
It would have been obvious to one of ordinary skill in the art at the time of the invention to modify the method of MNT to include gold nanoparticles as taught by Hangzhou for the purpose of providing materials and structures for sensing a target molecule with a quick response, strong anti-interference capability, high sensitivity, and good stability (Hangzhou, abstract).
Regarding Claim 10, modified MNT discloses the method of any of claims 7-9, wherein the minimally invasive wearable technology further includes sensing interfaces built on the lip of shortened gold needles (Para. 0040: For specificity, the first microneedle set 22 [shortened needles] may be subjected to surface modification, in view of the target molecule to be sensed [sensing interfaces]...For coupling of an antibody or an aptamer [sensing interfaces], self-assembled monolayer (SAM) may be applied to the microneedle deposited with gold; Para. 0042: a biotinylated ssDNA aptamer [sensing interfaces] on a surface of the microneedle of streptavidin-modified electrode is suitable to measure the concentration of tetracycline, wherein the biolinylaled ssDNA aptamer has specificity to tetracycline).
MNT fails to explicitly disclose acupuncture needles.
Hangzhou teaches acupuncture needles (Para. 0022: The invention also aims to provide an acupuncture needle imprinting electrochemical sensor for detecting dopamine).
Therefore, ii would have been ii would have been obvious to one of ordinary skill in the art at the lime the invention was made to teach acupuncture needles, since a mere duplication of essential working parts of a device involves only routine skill in the art. The motivation for doing so would have been to provide low priced needles with simple and convenient operation aspects and is widely applied in the medical field (Hangzhou, Para. 0005).
Allowable Subject Matter
Claims 13-15 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Regarding claim 13, the prior art of record, individually or in combination, does not teach or fairly suggest the method of claim 7, wherein the minimally-invasive wearable technology includes a hydrogel-embedded hollow microneedle interface, where the hydrogel simultaneously and uniquely renders an !SF-to-sensor analyte diffusion pathway, a micro-controlled aqueous medium for fouling-resistive sensing, sensor protection, and ease of integration with planar sensors.
The closest prior art, University of Cincinnati (WO 2020/146043 A1) teaches he minimally-invasive wearable technology includes a hydrogel-embedded hollow microneedle interface (Para. 0058: With reference to FIG. 4, where like numerals refer to like features previously shown and described for FIGS. 1A, 1B, and 2, an alternative embodiment of the invention is shown for a device 200. The device 200 is placed partially in-vivo into the skin 12 comprised of the epidermis 12a, dermis 12b, and the subcutaneous or hypodermis 12c. A portion of the device 200 accesses invasive fluids such as interstitial fluid from the dermis 12b and/or blood from a capillary 12d. Access is provided, for example, microneedles 212 [minimally-invasive wearable tech] formed of metal, polymer, semiconductor, glass or other suitable material, and may include a hydrogel 232 [hollow lumen, Fig. 4] that contributes to a sample volume), where the hydrogel simultaneously and uniquely renders an !SF-to-sensor analyte diffusion pathway (Para. 0050: With further reference to FIG. 1A...A diffusion pathway exists from the invasive biofluid such as interstitial fluid or blood to the sensor probes 120), but fails to explicitly teach a micro-controlled aqueous medium for fouling-resistive sensing, sensor protection, and ease of integration with planar sensors.
Regarding claim 14, the prior art of record, individually or in combination, does not teach or fairly suggest the method of claim 7, wherein the minimally-invasive wearable technology includes generalizable sensing interfaces with built-in signal enhancement features to continuously track electroactive and non-electroactive drugs.
The closest prior art, Micro Nipple Technology Co., Ltd. (US 2015/0208985 A1) teaches minimally-invasive wearable technology includes generalizable sensing interfaces (Para. 0040: For specificity, the first microneedle set 22 [minimally-invasive wearable technology] may be subjected to surface modification, in view of the target molecule to be sensed [sensing interfaces]...For coupling of an antibody or an aptamer [sensing interfaces], self-assembled monolayer (SAM) may be applied to the microneedle deposited with gold) with built-in signal features to continuously track drugs (Para. 0028: The signal processing unit 41 electrically connects to the microneedle unit 20 and receives a concentration data of hypodermal target molecules sensed by the microneedle unit 20. The signal processing unit 41 generates a sensing signal manifesting the current physiological condition of user after processing the received concentration data; Para. 0042: the transdermal microneedle array patch of the present invention may be used for pharmaceutical monitoring during the administration of a medication for a chronic disease or a specific pharmaceutical), but fails to explicitly teach built-in signal enhancement features to continuously track electroactive and non-electroactive drugs.
Regarding claim 15, the prior art of record, individually or in combination, does not teach or fairly suggest the method of claim 7, further comprising: using machine learning-based algorithms to mitigate the effect of confounders and to render personalized and predictive estimates of the drug's PK profile.
The closest prior art, Glauser et al. (US 2009/0171697 A1) teaches algorithms to render personalized and predictive estimates of the drug's PK profile (Para.0037: The invention provides population models for various compounds that incorporate pharmacokinetic and pharmacodynamic models of drug action and interpatient variability. Further the invention provides computerized methods and/or computer-assisted methods (including software algorithms) that utilize the one or more population models of the invention to predict a dosing regimen for a particular compound or to predict patient response to a compound; Para. 0059: The exemplary software program of the invention employs Bayesian methods.
The Bayesian methods allow fewer drug measurements for individual PK parameter estimation, sample sizes (e.g. one sample), and random samples. Therapeutic drug monitoring data, when applied appropriately, can also be used to detect and quantify clinically relevant drug-drug interactions), but fails to explicitly teach using machine learning-based algorithms to mitigate the effect of confounders and to render personalized and predictive estimates of the drug's PK profile.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOSEPH M SANTOS RODRIGUEZ whose telephone number is (571)270-7782. The examiner can normally be reached Monday-Friday 8:30am to 5:30pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Anne M. Kozak can be reached at 571-270-0552. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/JOSEPH M SANTOS RODRIGUEZ/Primary Examiner, Art Unit 3797
Prosecution Insights