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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 12/19/2025 has been entered.
Response to Amendment
The Amendment filed 12/19/2025 has been entered. Claims 1-6, 8, 9, 11, 12 and 14-23 remain pending in the application. Applicant’s amendments to the Claims have overcome each and every 112(a) and 112(b) rejections previously set forth in the Final Office Action mailed 9/22/2025.
Claim Rejections - 35 USC § 103
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 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) 1, 2, 4-6, 8, 9, 18, 19 and 21 are rejected under 35 U.S.C. 103 as being unpatentable over Francis et al. (US 2015/0141910 A1) in view of Park et al. (US 2019/0329035 A1) and further in view of Xu et al. (US 2021/0346665 A1).
Regarding claims 1, 8 and 9, Francis discloses an electrically conductive and electricity-driven drug delivery system (figure 2) comprising:
an electrically conductive drug delivery device 10 comprising an array of microprotrusions (paragraph 0030, lines 1-2, “microneedle array”) each comprising one or more polymers (paragraph 0067, lines 2-12), and substances or molecules to be delivered to a target site of a recipient (paragraph 0034, lines 1-4) when a tip section (portion of element 26 that gets first inserted into the patient’s body) of each of the microprotrusions 26 contacts a surface (surface of element 30) of the target site of the recipient under an electrical stimulation (paragraph 0007), wherein the substances or molecules comprise a nucleic acid or a protein, a peptide, or a fragment thereof (paragraph 0027, lines 5-8, “cross-linked synthetically derived protein”); and
an electric circuit (paragraph 0003, lines 5-7, “circuitry”) connecting the electrically conductive drug delivery device to provide an electric current to the array of the microprotrusions 26 configured to provide a first electric current sufficient to induce an electro-osmosis of the substances or molecules to the recipient (paragraph 0028, lines 6-15) but is silent regarding each comprising an electrically conductive component, wherein the electrically conductive component comprises one or more of PEDOT:PSS, polythiophene (PTh), carbon nano tube, polypyrrole (PPy), polyaniline, and Mxene, wherein the electrically conductive component is in a concentration of about 0.1 wt.% to 90wt.% in the array of microprotrusions.
However, Xu teaches teaches a design of a conductive microneedle patch wherein the array of microprotrusions further comprises an electrically conductive component (paragraph 0104, lines 1-6), wherein the electrically conductive component comprises one or more of PEDOT:PSS (paragraph 0154, lines 1-9), polythiophene (PTh), carbon nano tube, polypyrrole (PPy), polyaniline, and Mxene, wherein the electrically conductive component is in a concentration of about 0.1 wt.% to 90wt.% (paragraph 0105, lines 1-5) in the array of microprotrusions for the purpose of enhancing the delivery of the active ingredients by conducting the electricity (paragraph 0104, lines 6-18) and achieving a homogenous distribution throughout the matrix when the conductive polymer is doped therein (paragraph 0105, lines 5-8).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art, before the effective filing of the claimed invention to modify the array of microprotrusions of Francis to incorporate wherein the array of microprotrusions further comprises an electrically conductive component, wherein the electrically conductive component comprises one or more of PEDOT:PSS, polythiophene (PTh), carbon nano tube, polypyrrole (PPy), polyaniline, and Mxene, wherein the electrically conductive component is in a concentration of about 0.1 wt.% to 90wt.% in the array of microprotrusions as taught by Xu for the purpose of enhancing the delivery of the active ingredients by conducting the electricity (paragraph 0104, lines 6-18) and achieving a homogenous distribution throughout the matrix when the conductive polymer is doped therein (paragraph 0105, lines 5-8).
Francis is further silent regarding an electric circuit connecting the electrically conductive drug delivery device to provide an electric potential to provide a constant negative voltage to induce an electro-osmosis of the substances or molecules to the recipient, followed by a millisecond pulse voltage to induce a micro-electroporation for transfection of the nucleic acid.
However, Park teaches an approach of performing an electroporation using an electroporation device comprising an electric circuit (paragraph 0002, lines 8-12, circuit that provides a negative voltage) connecting the electrically conductive drug delivery device to provide an electric potential to provide a constant negative voltage to induce an electro-osmosis of the substances or molecules to the recipient, and a millisecond pulse voltage (paragraph 0064, table 2) to induce a micro-electroporation for transfection of the nucleic acid (paragraph 0048) for the purpose of introducing the charged and large molecular mass (paragraph 0003, lines 7-9, paragraph 0004, lines 8-11).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art, before the effective filing of the claimed invention to modify the electric circuit of Francis to incorporate an electric circuit connecting the electrically conductive drug delivery device to provide an electric potential to provide a constant negative voltage to induce an electro-osmosis of the substances or molecules to the recipient, and a millisecond pulse voltage to induce a micro-electroporation for transfection of the nucleic acid as taught by Park for the purpose of introducing the charged and large molecular mass (paragraph 0003, lines 7-9, paragraph 0004, lines 8-11).
While Park does not disclose to combine electro-osmosis and transfection therefore, Park is silent regarding providing a constant negative voltage followed by a millisecond pulse voltage.
However, according to MPEP 2144.06 (I), it is well known to combine equivalents known for the same purpose and therefore, it would have been obvious to one of ordinary skill in the art to combine both approaches as taught by Park to thereby have a constant negative voltage followed by a millisecond pulse voltage to deliver the substances or molecules to the recipient.
Francis modified in view of Park would result in having induce a micro-electroporation for transfection of the nucleic acid at the same array of the microprotrusions.
Regarding claim 2, Francis teaches wherein the target site is skin 30, 32 of the recipient.
Regarding claim 4, Francis discloses wherein the one or more polymers are biocompatible and biodegradable (paragraph 0067, lines 2-12).
Regarding claim 5, Francis discloses wherein the one or more polymers comprise poly (lactic-co-glycolic acid) (PLGA), poly (glycolic acid) (PGA), poly-L-lactide (PLA), polyvinyl alcohol (PVA), polyvinylpyrrolidone (PVP) (paragraph 0067, lines 2-12).
Regarding claim 6, Francis discloses wherein the one or more polymers have a concentration of about 0.1wt.% to 60wt.% in the array of microprotrusions (paragraph 0067, lines 28-34).
Regarding claim 18, Francis discloses a method (paragraph 0028) for delivering substances or molecules to the target site of the recipient based on the microelectroporation and the electro-osmosis, the method comprising:
providing the electrically conductive and electricity-driven drug delivery system (figure 2);
contacting the tip section (section of element 26 that first enters into element 30 in figure 2) of the array of the microprotrusions 26 with the surface (surface of element 30) of the target site 30, 32 of the recipient;
triggering release of the substances or molecules from the tip section of the array of the microprotrusions by the electro-osmosis to the target site through the microprotrusions under the electric current provided by the electric circuit (paragraph 0003, lines 5-7).
Francis is silent regarding triggering release of the substances or molecules under the constant negative voltage and initiating the micro-electroporation for the transfection of the nucleic acid under the millisecond pulse voltage provided by the electric circuit at the same tip section of the array of the microprotrusions.
However, Park teaches triggering (paragraph 0002, lines 8-12) release of the substances or molecules under the constant negative voltage and initiating (paragraph 0064, table 2) the micro-electroporation for the transfection of the nucleic acid under the millisecond pulse voltage provided by the electric circuit for the purpose of introducing the charged and large molecular mass (paragraph 0003, lines 7-9, paragraph 0004, lines 8-11).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art, before the effective filing of the claimed invention to modify the method of Francis to incorporate triggering release of the substances or molecules under the constant negative voltage and initiating the micro-electroporation for the transfection of the nucleic acid under the millisecond pulse voltage provided by the electric circuit as taught by Park for the purpose of introducing the charged and large molecular mass (paragraph 0003, lines 7-9, paragraph 0004, lines 8-11).
Francis modified in view of Park will result in having triggering release of the substances or molecules under the constant negative voltage and initiating the micro-electroporation for the transfection of the nucleic acid under the millisecond pulse voltage provided by the electric circuit at the same tip section of the array of the microprotrusions (see MPEP 2144.06 (I), it is obvious to combine equivalents known for the same purpose i.e. deliver the substances or molecules into the recipient).
Regarding claim 19, Francis is silent wherein the constant negative voltage or the millisecond pulse voltage is the electric potential from 1nV to 500 V or the electric potential of a pulse voltage from 1mV to 200 V at a pulse duration from about 1 ms to 10s.
However, Park teaches wherein the constant negative voltage or the millisecond pulse voltage is the electric potential from 1nV to 500 V or the electric potential of a pulse voltage from 1mV to 200 V at a pulse duration from about 1 ms to 10s (paragraph 0062, lines 8-14, paragraph 0064, Table 2) for the purpose of introducing the charged and large molecular mass (paragraph 0003, lines 7-9, paragraph 0004, lines 8-11).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art, before the effective filing of the claimed invention to modify the method of Francis to incorporate wherein the constant negative voltage or the millisecond pulse voltage is the electric potential from 1nV to 500 V or the electric potential of a pulse voltage from 1mV to 200 V at a pulse duration from about 1 ms to 10s as taught by Park for the purpose of introducing the charged and large molecular mass (paragraph 0003, lines 7-9, paragraph 0004, lines 8-11).
Regarding claim 21, Francis discloses the claimed invention substantially as claimed, as set forth above in claim 18. Francis further discloses wherein the target site of the recipient comprises skin 30, 32, oral mucous membrane, gastrointestinal mucosa membrane, or external or internal mucosa membrane of organs, and wherein the recipient is a mouse, a rat, a pig, a rabbit, a frog, a cattle, a horse, a non-human primate animals or a human (Francis discloses the use for human as evidenced from the entire specification).
Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over Francis et al. (US 2015/0141910 A1) in view of Park et al. (US 2019/0329035 A1) in view of Xu et al. (US 2021/0346665 A1) and further in view of Bao et al. (“Recent advances in porous microneedles: materials, fabrication, and transdermal applications”, 2021).
Regarding claim 3, Francis/Park/Xu (hereinafter referred as “modified Francis”) discloses the claimed invention substantially as claimed, as set forth above in claim 1. Francis discloses wherein the array of the microprotrusions 26 comprise microporous structure (paragraph 0034, lines 10-14, “porous”) but is silent regarding wherein the microporous structure has an average pore size of about 1 nm to 200 µm.
However, Bao teaches a design of a microprotrusion comprising a porous structure wherein the microporous structure has an average pore size of about 1 nm to 200 µm (see page 400, second column, under material title: “Poly (lactic-co-glycolic acid)”, “pore diameters ranging from 1.9 to 15 µm“) for the purpose of achieving drug delivery (see page 400, second column, under material title: “Poly (lactic-co-glycolic acid)”) by enabling drug transport through channel-like connected pores by capillary action (page 397, first column, lines 27-31).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art, before the effective filing of the claimed invention to modify the pore size of the microporous structure of modified Francis to incorporate wherein the microporous structure has an average pore size of about 1 nm to 200 µm as taught by Bao for the purpose of achieving drug delivery (see page 400, second column, under material title: “Poly (lactic-co-glycolic acid)”) by enabling drug transport through channel-like connected pores by capillary action (page 397, first column, lines 27-31).
Claim 12 is rejected under 35 U.S.C. 103 as being unpatentable over Francis et al. (US 2015/0141910 A1) in view of Park et al. (US 2019/0329035 A1) in view of Xu et al. (US 2021/0346665 A1) and further in view of Han et al. (US 2018/0344997 A1).
Regarding claim 12, modified Francis discloses the claimed invention substantially as claimed, as set forth above in claim 1. Modified Francis is silent regarding wherein the nucleic acid is loaded into each of the microprotrusions at a weight of about 1pg to 100 g.
However, Han teaches a design of a water-soluble microneedle wherein the nucleic acid is loaded into each of the microprotrusions at a weight of about 1pg to 100 g (paragraph 0184, “mixture of DNA and RNA fragments (2mg)”) for the purpose of delivering effective material to achieve desired health benefit (paragraph 0004).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art, before the effective filing of the claimed invention to modify the substance or molecules of modified Francis to incorporate wherein the nucleic acid is loaded into each of the microprotrusions at a weight of about 1pg to 100 g as taught by Han for the purpose of delivering effective material to achieve desired health benefit (paragraph 0004).
Claim 11 is rejected under 35 U.S.C. 103 as being unpatentable over Francis et al. (US 2015/0141910 A1) in view of Park et al. (US 2019/0329035 A1) in view of Xu et al. (US 2021/0346665 A1) and further in view of Wolff et al. (US 5,693,622).
Regarding claim 11, modified Francis discloses the claimed invention substantially as claimed, as set forth above in claim 1. Modified Francis is silent regarding wherein the nucleic acid is a nucleic acid-based vaccine comprising a DNA or RNA vaccine, wherein the RNA vaccine comprise a linear or circular mRNA vaccine, and wherein the DNA vaccine comprises a DNA plasmid capable of expressing one or more antigenic proteins in the recipient.
However, Wolff teaches a method of delivering pharmaceutical polypeptide wherein the nucleic acid is a nucleic acid-based vaccine comprising a DNA or RNA vaccine (column 16, lines 29-32), wherein the RNA vaccine comprise a linear or circular mRNA vaccine (column 8, lines 24-28), and wherein the DNA vaccine comprises a DNA plasmid (column 9, lines 15-17) capable of expressing one or more antigenic proteins in the recipient (column 16, lines 35-39) for the purpose of providing improved and effective immunity against infectious agents (column 16, lines 35-39).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art, before the effective filing of the claimed invention to modify the substance or molecule of modified Francis to incorporate wherein the nucleic acid is a nucleic acid-based vaccine comprising a DNA or RNA vaccine, wherein the RNA vaccine comprise a linear or circular mRNA vaccine, and wherein the DNA vaccine comprises a DNA plasmid capable of expressing one or more antigenic proteins in the recipient as taught by Wolff for the purpose of providing improved and effective immunity against infectious agents (column 16, lines 35-39).
Claim(s) 14 and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Francis et al. (US 2015/0141910 A1) in view of Park et al. (US 2019/0329035 A1) in view of Xu et al. (US 2021/0346665 A1) and further in view of Smith (US 2008/0033338 A1).
Regarding claims 14 and 15, modified Francis discloses the claimed invention substantially as claimed, as set forth above in claim 1. Modified Francis is silent regarding wherein the electric circuit comprises a negative electrode, a connection between the negative electrode and the electrically conductive drug delivery device, and a power supply, wherein the negative electrode comprises one or more conductive materials of copper, silver, iron, tin and aluminum.
However, Smith teaches a design of a device to deliver the drug via electroosmosis (figure 1) wherein the electric circuit (circuitry formed by elements 116, 124, 168) comprises a negative electrode (paragraph 0049, lines 1-5), a connection between the negative electrode 168 and the electrically conductive drug delivery device 100, and a power supply 116, wherein the negative electrode comprises one or more conductive materials of copper, silver, iron, tin and aluminum (paragraph 0056, lines 1-5) for the purpose of delivering the substance or molecules using the electric current (paragraph 0051, lines 1-7).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art to modify the electric circuit of modified Francis to incorporate wherein the electric circuit comprises a negative electrode, a connection between the negative electrode and the electrically conductive drug delivery device, and a power supply, wherein the negative electrode comprises one or more conductive materials of copper, silver, iron, tin and aluminum as taught by Smith for the purpose of delivering the substance or molecules using the electric current (paragraph 0051, lines 1-7).
Claim(s) 14, 16 and 17 are rejected under 35 U.S.C. 103 as being unpatentable over Francis et al. (US 2015/0141910 A1) in view of Park et al. (US 2019/0329035 A1) in view of Xu et al. (US 2021/0346665 A1) and further in view of Seitz (US 2010/0137779 A1).
Regarding claims 14 and 16, modified Francis discloses the claimed invention substantially as claimed, set forth above in claim 1. Modified Francis is silent regarding wherein the electric circuit comprises a negative electrode, a connection between the negative electrode and the electrically conductive drug delivery device, and a power supply, wherein the connection is a pair of magnetic clips for securing the electrically conductive drug delivery device to the negative electrode.
However, Seitz teaches a design of a system to electrically power to deliver the drug wherein the electric circuit (figure 2, circuit formed by elements 36, 30a, 30b, 28a, 28b) comprises a negative electrode 20b, a connection (connection formed by elements 28b, 30b, 30a, 28a) between the negative electrode 20b and the electrically conductive drug delivery device 12 (although element 20b is present in element 12, element 20b is not connected electrically to element 12 due to lack of connection provided by element 14), and a power supply 30, wherein the connection is a pair of magnetic clips 24a, 24b for securing the electrically conductive drug delivery device 12 for the purpose of securing two components together using magnetic power (paragraph 0017).
Examiner further construes that while Francis discloses the use of at least one electrode but is silent regarding connection between the electrodes and the microneedles. Seitz discloses magnetic coupling as one possible method of coupling two components together. Therefore, one of ordinary skill in the art could use the magnetic coupling to secure the electrically conductive drug delivery device to the negative electrode.
Therefore, it would have been prima facie obvious to one of ordinary skill in the art, before the effective filing of the claimed invention to modify the electric circuit of modified Francis to incorporate wherein the electric circuit comprises a negative electrode, a connection between the negative electrode and the electrically conductive drug delivery device, and a power supply, wherein the connection is a pair of magnetic clips for securing the electrically conductive drug delivery device to the negative electrode as taught by Seitz for the purpose of securing two components together using magnetic power (paragraph 0017).
Regarding claim 17, modified Francis discloses the claimed invention substantially as claimed, as set forth above in claim 1. Modified Francis is silent regarding wherein the power supply connects to the negative electrode and the electrically conductive drug delivery device, respectively, to provide the electric potential from 1nV to 500 V or the electric potential of a pulse voltage from 1mV to 200 V at a pulse duration from about 1 ms to 10 s, or to provide an electric current by the electric potential from 1nA to 500 A.
However, Seitz teaches wherein the power supply 30 connects to the negative electrode 20b and the electrically conductive drug delivery device, respectively, to provide the electric potential from 1nV to 500 V (paragraph 0146, lines 6-8) or the electric potential of a pulse voltage from 1mV to 200 V at a pulse duration from about 1 ms to 10 s, or to provide an electric current by the electric potential from 1nA to 500 A for the purpose of providing sufficient voltage and current to ensure delivery of the one or more active ingredients across a biological interface (paragraph 0146, lines 1-6).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art, before the effective filing of the claimed invention to modify the electric circuit of Francis to incorporate wherein the power supply connects to the negative electrode and the electrically conductive drug delivery device, respectively, to provide the electric potential from 1nV to 500 V or the electric potential of a pulse voltage from 1mV to 200 V at a pulse duration from about 1 ms to 10 s, or to provide an electric current by the electric potential from 1nA to 500 A as taught by Seitz for the purpose of providing sufficient voltage and current to ensure delivery of the one or more active ingredients across a biological interface (paragraph 0146, lines 1-6).
Claim(s) 20 is rejected under 35 U.S.C. 103 as being unpatentable over Francis et al. (US 2015/0141910 A1) in view of Park et al. (US 2019/0329035 A1) in view of Xu et al. (US 2021/0346665 A1) and further in view of Milleret et al. (US 2016/0230197 A1).
Regarding claim 20, modified Francis discloses the claimed invention substantially as claimed, as set forth above in claim 18. Modified Francis ’10 is silent regarding wherein the target site of the recipient comprises 3D cultured cell hydrogel bulk, and wherein the 3D cultured cell hydrogel bulk comprises one or more of gelatin-based hydrogel, alginate-based hydrogel, chitosan-based hydrogel, and PEG-based hydrogel.
However, Milleret teaches a method and system for producing a hydrogel wherein the target site of the recipient comprises 3D cultured cell hydrogel bulk, and wherein the 3D cultured cell hydrogel bulk comprises one or more of gelatin-based hydrogel, alginate-based hydrogel, chitosan-based hydrogel, and PEG-based hydrogel (paragraph 0131) for the purpose of using 3D engineered tissues to allow physiological studies and development of regenerative therapies (paragraph 0002, lines 1-2).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art, before the effective filing of the claimed invention to modify the target site of modified Francis to incorporate wherein the target site of the recipient comprises 3D cultured cell hydrogel bulk, and wherein the 3D cultured cell hydrogel bulk comprises one or more of gelatin-based hydrogel, alginate-based hydrogel, chitosan-based hydrogel, and PEG-based hydrogel as taught by Milleret for the purpose of using 3D engineered tissues to allow physiological studies and development of regenerative therapies (paragraph 0002, lines 1-2).
Response to Arguments
Applicant’s arguments with respect to claim 1 have been considered but are moot because the arguments do not apply in view of the present rejection.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NILAY J SHAH whose telephone number is (571)272-9689. The examiner can normally be reached Monday-Thursday 8:00 AM-4:30 PM EST.
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/NILAY J SHAH/Primary Examiner, Art Unit 3783