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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 03/10/2026 has been entered.
Withdrawal of Rejections
The response and amendments filed on 03/10/2026 are acknowledged. Any previously applied minor objections and/or minor rejections (i.e., formal matters), not explicitly restated here for brevity, have been withdrawn necessitated by Applicant’s formality correction and/or amendments. For the purposes of clarity of the record, the reasons for the Examiner’s withdrawal, and/or maintaining, if applicable, of the substantive or essential claim rejections are detailed directly below and/or in the Examiner’s Response to Arguments section.
Briefly, the previous claim rejections under 35 U.S.C. 103 for obviousness have been withdrawn necessitated by Applicant’s amendments; however, new grounds of rejection are set forth below.
The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 08/11/2026 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Rejections - 35 USC § 112(a), New Matter
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.
Claim 10-17, 20-25, 27-28, and 31-33 is rejected under 35 U.S.C. 112(a) as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 10 recites “adjusting a first valve positioned upstream of the aseptic sampling device to a first position to permit a flow of buffer”, “adjusting a second valve downstream of the aseptic sampling device to a first position to permit a flow of the substrate-containing buffer from the aseptic sampling device to a sample tube”, “the third valve is in a second position, prohibiting entry of the substrate-containing buffer to the microfluidic column sensor”, and “said introduction comprising adjusting the third valve to a first position”; however, there is no support in the instant specification as originally filed for adjusting a first, second, and third valve to allow or prohibit flow of the substrate-containing buffer. Therefore, recitation of these steps is new matter and should be removed from the instant claims (see, e.g., MPEP 608.04).
Claim 32 recites “wherein a concentration of the substrate in the buffer at the outlet of the aseptic sampling device is greater than the concentration of the substrate in the buffer at the inlet”; however, there is no support in the instant specification for the concentration of the substrate at the inlet and outlet of the aseptic sampling device in the instant specification as originally filed. Therefore, recitation of this is new matter and should be removed from the instant claims (see, e.g., MPEP 608.04).
Claims 11-17, 20-25, 27-28, 31, and 33 are included in this rejection for depending on rejected independent claim 10 and failing to rectify the noted deficiency.
Claim Rejections - 35 USC § 103, Obviousness
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 10-13, 15-17, 20-23, 27-28, and 31-33 are rejected under 35 U.S.C. 103 as being unpatentable over Tindal (Automated Glucose Control; 2017 – newly cited) in view of Govind (WO 2018/226907; Date of Publication: December 13, 2018 – cited in the IDS filed on 07/14/2023 – previously cited), Saxl (A fluorescence lifetime-based fibre-optic glucose sensor using glucose/galactose-binding protein; 2011 – cited in the IDS filed on 07/14/2023 – previously cited), and Gamble (U.S. Patent No. 7,178,386; Date of Publication: February 20, 2007 – previously cited).
Tindal’s general disclosure pertains to a method of controlling available glucose in automated feeding strategies in order to improve glycosylation patterns on final end products and improve quality (see, e.g., Tindal, Introduction, pg. 4).
Regarding claim 10 pertaining a method of measure a substrate in a sample solution for steps (a)-(b), Tindal teaches a method for controlling glucose using a machine called BioPAT Trace (see, e.g., Tindal, Materials and methods, pg. 4). The method comprises inserting a sampling device comprising a dialysis probe and membrane into a bioreactor comprising a sample solution, wherein the dialysis tube has an inlet and an outlet (see, e.g., Tindal, Figure 2). Tindal teaches that the sampling device, which comprises the dialysis probe, was sterilized (see, e.g., Tindal, Materials and methods, pg. 4); therefore, the dialysis probe is aseptic. Furthermore, Tindal teaches a first valve being upstream of the sampling device, which, when adjusted, would allow flow of the transport buffer into the dialysis tube (see, e.g., Tindal, Figure 2). Additionally, Tindal teaches that there is a second valve downstream of the first valve, as well as a check valve on the outlet of the microdialysis device (see, e.g., Tindal, Figure 2). Tindal teaches that the sample obtained from the microdialysis device is further sent to a measurement cell for further analysis (see, e.g., Tindal, Figure 2).
Regarding claim 12 pertaining to the sample solution, Tindal teaches that the sample is a Chinese Hamster Ovary cell culture media solution (see, e.g., Tindal, Materials and methods, pg. 4).
Regarding claim 20 pertaining to the method, Tindal teaches that the method of dialysis mode glucose and lactate measurement is a fully automated and self-calibrating protocol and the method can be performed continuously (see, e.g., Tindal, Materials and methods, pg. 5).
Regarding claim 23 pertaining to the aseptic sampling device, Tindal teaches that the method uses microdialysis (see, e.g., Tindal, Figure 2).
Regarding claim 32 pertaining to the concentration of substrate, Tindal teaches that transport buffer flows through tubing to the dialysis device that is inserted into a sample solution, wherein the transport buffer is then mixed with a substrate in the sample solution and leaves the aseptic sampling device via the outlet (see, e.g., Tindal, Figure 2). Therefore, one of ordinary skill in the art would readily understand that the concentration of substrate in the transport buffer is greater at the outlet than the inlet because the transport buffer enters the aseptic sampling device via the inlet, is mixed with substrate, and then leaves via the outlet.
Regarding claim 33 pertaining to adjusting valves, Tindal teaches that valves 1 and 2 can be adjusted which would allow bypass of the microdialysis sampling device (see, e.g., Tindal, Figure 2). One of ordinary skill in the art would readily understand that this would drive the transport buffer containing the substrate past the microdialysis device.
However, Tindal does not teach: (c) adjusting a second valve downstream of the aseptic sampling device to a first position to permit a flow of the substrate-containing buffer from the aseptic sampling device to a sample tube for collection therein, wherein the sample tube is positioned upstream of a microfluidic column sensor with a third valve positioned therebetween, wherein during collection of the substrate-containing buffer in the sample tube, the third valve is in a second position, prohibiting entry of the substrate- containing buffer to the microfluidic column sensor; (d) introducing the substrate-containing buffer collected in the sample tube to the to a microfluidic column sensor for fluorescence measurement, said introduction comprising adjusting the third valve to a first position, wherein the microfluidic column sensor which comprises a solid support comprising immobilized binding protein, wherein if any substrate is present in the substrate- containing buffer, it binds to the binding protein and an increase in fluorescence occurs; and (e) measuring the fluorescence using a fluorometer (claim 10); or wherein the microfluidic column sensor is packed with solid support by: introducing the solid support to the microfluidic column sensor, and flowing the binding protein to the solid support for a time necessary to effectuate immobilization of the binding protein to the solid support (claim 11); or wherein the flow rate is controlled by a syringe pump positioned upstream of the first valve (claim 13); or wherein (i) the flow rate, (ii) a diffusion surface area of the dialysis tube of the aseptic sampling device, or (iii) both (i) and (ii) can be used to determine the amount of substrate that can diffuse into the buffer in the dialysis tube aseptic sampling device and is available to bind to the binding protein in the microfluidic column sensor (claim 15); or wherein (i) the flow rate, (ii) the diffusion surface area of the dialysis tube of the aseptic sampling device, or (iii) both (i) and (ii) is controlled so that the measured fluorescence remains in a linear portion of a calibration curve (claim 16); wherein the increase in fluorescence is a function of the concentration of substrate bound to the binding protein (claim 17); or wherein the microfluidic column sensor has a volume of about 0.1 to about 200 µL (claim 21); or wherein the solid support is in the form of beads, spheres, particles, granules, a gel, or a surface (claim 22); or wherein the substrate is glucose and the binding protein is a glucose binding protein (claim 27); or wherein the solid support comprises nickel- nitrilotriacetic acid (Ni-NTA) agarose beads (claim 28); or wherein subsequent to the fluorescence measurement, continued introduction of buffer to the sample tube and the microfluidic column sensor elutes the substrate from the binding protein (claim 31).
Govind’s general disclosure relates to “a fully integrated microfluidic system capable of producing single-dose amounts of biotherapeutics at the point-of-care wherein protein production, purification and product harvest are all integrated as a single microfluidic device which is portable and capable of continuous-flow production of biotherapeutics at the microscale using a cell-free reaction system” (see, e.g., Govind, abstract). Moreover, Govind discloses that the microfluidic device can capture proteins through substrate binding to binding proteins within chromatography columns (see, e.g., Govind, [0104]), wherein the protein binding can be analyzed using fluorescence (see, e.g., Govind, [0048]).
Regarding claim 10 pertaining to steps (d)-(e), Govind teaches adding the sample to the apparatus, wherein the sample is added to the chromatography column (i.e., microfluidic column) in wash buffer (see, e.g., Govind, [0028]-[0029] & [0104]). Moreover, Govind teaches loading protein, such as GCSF, into the column using a syringe pump to control the flow rate, wherein the flow rate is 0.2 mL/min (see, e.g., Govind, [0104]). Govind teaches that the apparatus can comprise a sensor that measures fluorescence (see, e.g., Govind, [0048]).
Regarding claim 11 pertaining to introducing the solid support, Govind teaches introducing a chromatography resin, wherein the resin is preferably an immobilized metal affinity resin and/or an ion exchange resin (see, e.g., Govind, [0014]).
Regarding claim 13 pertaining to the syringe pump, Govind teaches loading protein, such as GCSF, into the column using a syringe pump to control the flow rate, wherein the flow rate is 0.2 mL/min (see, e.g., Govind, [0104]).
Regarding claim 15 pertaining to the flow rate and the amount of substrate binding to binding protein, Govind teaches that “controlled pumping the lysate into the column at an efficiently monitored flow rate would improve the binding” (see, e.g., Govind, [0028]) and “Slightly better controlled pumping of the lysate into the column with a monitored flow rate slightly improved the binding of GFP” (see, e.g., Govind, [0029]). Moreover, Govind teaches equation 5, wherein the diffusion coefficient can be used to solve for the concentration of the particle (see, e.g., Govind, [0098]). Equation 5 also takes into account the concentration of the species (i.e., solute) within the fluid, as well as the fluid velocity (i.e., flow rate) (see, e.g., Govind, [0097]). Additionally, Govind teaches equations 3-4, wherein the diffusion coefficient can be used to solve for the concentration of species in the fluid, wherein the species (i.e., substrate) is available to bind to the binding protein (see, e.g., Govind, [0097]). One of ordinary skill in the art would understand that they can solve the equations set forth by Govind, wherein the flow rate and diffusion can be used to solve for the concentration of substrate that is available to bind to the binding protein. Moreover, one of ordinary skill in the art would readily understand that controlling the flow rate of the substrate, and knowing the starting amount of substrate, would allow for one to determine the amount of substrate that is available to bind to the binding protein, and controlling the flow rate will improve binding, based on the teachings of Govind (see, e.g., Govind, [0028]).
Regarding claim 16 pertaining to controlling the flow rate, Govind teaches controlling the flow rate effectively through the use of a syringe pump, wherein the flow rate is 0.2 mL/min (see, e.g., Govind, [0012], [0104]). One of ordinary skill in the art would recognize that controlling the flow rate would control the amount of protein binding to the binding protein on the chromatography columns, which would control the amount of fluorescence.
Regarding claim 21 pertaining to the volume of the microfluidic column, Govind teaches that the microfluidic columns can hold a volume ranging from 25-200 µL (see, e.g., Govind, [0014]).
Regarding claim 22 pertaining to the solid support, Govind teaches that the solid support can be “spherical beads with affinity ligands bound to the bead surfaces, wherein the beads are formed of cellulose, poly-styrene-divinylbenzene copolymer, polymethylmethacrylate, or other suitable material” (see, e.g., Govind, [0052]).
Regarding claim 31 pertaining to elution of the substrate from the binding protein, Govind teaches that within the microfluidic chromatography chip, elution buffer is added and flowed through the collection tube and column, wherein proteins bound to the microfluidic column are eluted due to the introduction of the elution buffer (see, e.g., Govind, [0028]-[0029] & Figures 8-9).
Saxl’s general disclosure relates to “fibre-optic biosensors using glucose/galactose binding protein (GBP) labelled with the environmentally sensitive fluorophore, Badan. GBP–Badan was attached via an oligohistidine-tag to the surface of Ni–nitrilotriacetic acid (NTA)-functionalized agarose or polystyrene beads. Fluorescence lifetime increased in response to glucose, observed by fluorescence lifetime imaging microscopy of the GBP–Badan-beads. Either GBP–Badan agarose or polystyrene beads were loaded into a porous chamber at the end of a multimode optical fibre. Fluorescence lifetime responses were recorded using pulsed laser excitation, high speed photodiode detection and time-correlated single photon counting” (see, e.g., Saxl, abstract). Moreover, Saxl discloses that glucose binding to glucose binding protein results in fluorescence as a readout and can be correlated to glucose concentration within a sample (see, e.g., Saxl, Figures 2-3). Furthermore, Saxl teaches that fluorescence-based monitoring of substrate levels “has the advantages of sensitivity and lack of electrochemical interference” (see, e.g., Saxl, Introduction, pg. 968).
Regarding claim 10, part (c) pertaining to the binding of the substrate of the binding protein resulting in increased fluorescence, Saxl teaches that the addition of glucose, and the binding of glucose-to-glucose binding protein, results in increased fluorescence (see, e.g., Saxl, Figures 2-3). Moreover, Saxl teaches that upon binding to glucose, glucose binding protein undergoes a large change in molecular conformation “which can be detected by either fluorescence resonance energy transfer or by labelling with an environmentally sensitive fluorophore” (see, e.g., Saxl, Introduction, pg. 968).
Regarding claim 11 pertaining to immobilizing the binding protein to the solid support, Saxl teaches that the Ni-NTA agarose beads were incubated with glucose binding protein for four hours (see, e.g., Saxl, “Attachment of GBP-Badan to agarose or polystyrene beads”, pg. 970-971).
Regarding claim 17 pertaining to fluorescence and substrate concentration, Saxl teaches that the concentration of the substrate is positively correlated to fluorescence (see, e.g., Saxl, Figure 2 & Results, pg. 970). Furthermore, increased glucose results in increased binding to glucose binding protein, thereby resulting in increased fluorescence (see, e.g., Saxl, Figures 2-3).
Regarding claim 27 pertaining to the substrate and binding protein, Saxl teaches that the substrate is glucose and the binding protein is glucose binding protein (see, e.g., Saxl, Introduction & Figure 2 & Results, pg. 970).
Regarding claim 28 pertaining to the solid support, Saxl teaches that the solid support is Ni-NTA polystyrene beads (see, e.g., Introduction & Results, pg. 970). Furthermore, Saxl teaches that the sensor’s “response was best conserved using Ni-NTA functionalized agarose beads as an immobilization strategy” and the immobilization of glucose binding protein to Ni-NTA does not impair the fluorescence response to glucose (see, e.g., Saxl, Conclusion, pg. 972).
Gamble’s general disclosure relates to “A parallel fluid processing system including multiple fluid process regions containing solid material in fluid communication with a common first fluid source may be used to conduct analyses and/or synthesis in parallel. A parallel fluid processing data correction method includes supplying and processing a calibrant in each fluid process region, measuring a first physical parameter and deriving at least one correction factor based on the parameter, supplying and processing at least one second fluid in each fluid process region, and then applying the correction factor to yield corrected process data. Retention time correction, peak area correction, and other useful data corrections may be performed. Parallel fluid processing may be performed with microfluidic devices and systems” (see, e.g., Gamble, abstract).
Regarding claim 10 pertaining to step (c), Gamble teaches method of fluid processing wherein a sample source (see, e.g., Gamble, Figure 2, Sample Source 40), which one of ordinary skill in the art would recognize can be a sample tube, is positioned upstream of a column with a first rotary valve positioned in between (see, e.g., Gamble, Figure 2). Additionally, Gamble teaches that the rotary valve can be controlled to inject a predetermined about of sample from the sample source into the column (see, e.g., Gamble, pg. 31, col. 3, lines 37-40). One of ordinary skill in the art would readily understand that if the valve can inject a predetermined amount of sample, that the valve can be opened and closed in order to prohibit entry or allow entry of the substrate-containing buffer into the column
It would have been first obvious to one of ordinary skill in the art to combine Tindal’s method of transporting a sample through a microdialysis device via tubes and valves with Govind’s method of analyzing a sample with a microfluidic column. One would have been motivated to do so because Govind teaches that the microfluidic columns comprise solid supports with immobilized binding protein (see, e.g., Govind, [0051]-[0053]) and Govind teaches a method of connecting a sampling device to the column to allow for protein capture so that a sensor can measure protein fluorescence (see, e.g., Govind, [0048]-[0049]). Therefore, based on these teachings, it would have been obvious to transport a protein sample to a microfluidic column in order to capture and analyze proteins using fluorescence. Additionally, based on these teachings, it would have been obvious to substitute Tindal’s measurement cell with Govind’s microfluidic column in order to transport sample via tubes and values to a microfluidic column for subsequent analysis. Furthermore, Tindal teaches a method of using valves and tubes to transport sample, which would have been obvious to use to transport sample to a microfluidic column because this would allow for the controlled transport of sample from a source through tubes, wherein a predetermined amount of sample can be allowed into the microfluidic column via control of the valve(s). Moreover, the valves can also allow or prohibit entry of sample from the tubes into the microfluidic column via the valves. Therefore, it would have been obvious to further analyze a protein sample using a microfluidic column, wherein the sample is transported to the microfluidic column via tubes and wherein valves are used to control, allow, and/or prohibit entry of the protein sample into the microfluidic column.
It would have been secondly obvious to combine Tindal’s method of transporting a sample through a microdialysis device via tubes and valves, wherein the flow rate of the sample is controlled by a syringe, as taught by Govind. One would have been motivated to do so because Govind teaches a syringe pump is used to control the flow rate (see, e.g., Govind, [0104]), and controlled pumping the lysate into the column at an efficiently monitored flow rate would improve the binding” (see, e.g., Govind, [0028]). Therefore, it would have been obvious to use a syringe to pump the sample through Tindal’s microdialysis device and into a Govind’s microfluidic column in order to control the flow rate of the sample because controlled pumping into the column allows for improved binding of the sample to the column. One would have expected success because Tindal and Govind both teach methods of fluid processing wherein the sample(s) comprise glucose.
It would have been thirdly obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine Tindal’s method of transporting a sample through a microdialysis device via tubes and valves with Saxl’s method of analyzing the concentration of glucose in the sample by binding to glucose protein using Ni-NTA chromatography columns. One would have been motivated to do so because Saxl teaches that Ni-NTA is used for immobilization of glucose binding protein within the column in order to allow for glucose binding protein to bind to glucose within the sample (see, e.g., Saxl, Introduction, pg. 969 & Results and Discussion, pg. 969). Moreover, Saxl teaches that the sensor’s “response was best conserved using Ni-NTA functionalized agarose beads as an immobilization strategy” and the immobilization of glucose binding protein to Ni-NTA does not impair the fluorescence response to glucose (see, e.g., Saxl, Conclusion, pg. 972). Therefore, based on these teachings it would have been obvious to use Ni-NTA within the chromatography columns to immobilize glucose binding protein for binding to glucose within a sample. One would have expected success because Tindal and Saxl both teach methods of measuring glucose levels in a sample.
It would have been fourthly obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine Tindal’s method of transporting a sample through a microdialysis device via tubes and valves with Gamble’s method of fluid processing wherein a valve is located upstream of a column. One would have been motivated to do so because Gamble teaches that the rotary valve can be controlled to inject a predetermined about of sample from the sample source into the column (see, e.g., Gamble, pg. 31, col. 3, lines 37-40). Therefore, it would be obvious to put a valve between the microdialysis device and the column in order to control the amount of sample that enters the column and to be able to allow and prohibit entry of the sample into the column. One would have expected success because both Tindal and Gamble both teach methods of fluid processing wherein samples are processed through tubing and valves.
Claims 14 and 24-25 are rejected under 35 U.S.C. 103 as being unpatentable over Tindal, Govind, Saxl and Gamble as applied to claims 10-13, 15-17, 20-23, and 27-28 above, and further in view of Kostov (Portable system for the detection of micromolar concentrations of glucose; 2014 – cited in the IDS filed on 07/14/2023 – previously cited).
The references of Tindal, Govind, Saxl and Gamble are discussed above as it pertains to a method of measuring the concentration of a substrate.
However, the references do not teach: determining the concentration of the concentration of the substrate in the sample solution using the measured fluorescence and a calibration curve (claim 14); or wherein the fluorometer is a microfluorometer (claim 24); or wherein the microfluidic sensor is positioned flush with the fluorimeter to facilitate fluorescent measurements (claim 25).
Kostov’s general disclosure relates to “a USB powered, all-solid-state, hand-held fluorometric system for measurement of low glucose concentrations. It utilizes the dual-labeled GBP as sensor and a dedicated low cost, dual emission microfluorometer” (see, e.g., Kostov, Introduction, pg. 2). Moreover, Kostov discloses the construction of calibration curves in order to measure the concentration of substrate within a sample, such as the amount of glucose within a biological sample (see, e.g., Kostov, Results and Discussion, pgs. 7-9 & Figures 5-6).
Regarding claim 14 pertaining to determine the concentration of the substrate, Kostov teaches constructing a calibration curve (see, e.g., Kostov, “Calibration”, pg. 6) and using the measured fluorescence to determine the concentration of the substrate within the sample (see, e.g., Kostov, Results and Discussion, pgs. 7-9 & Figures 5-6).
Regarding claim 24 pertaining to the microfluorometer, Kostov teaches using a dual emission microfluorometer (see, e.g., Kostov, Introduction, pg. 2). Moreover, Kostov teaches that using a microfluorometer system is a promising tool for accurate measurements of low glucose concentrations in biological samples (see, e.g., Kostov, Conclusion, pg. 9).
Regarding claim 25 pertaining to the column being flush with the fluorimeter, Kostov teaches that the fluorometric system contains a cuvette, which holds the sample, and a microfluorometer, wherein the cuvette holding the sample is sandwiched between the photodiodes of the microfluorometer (see, e.g., Kostov, “Optics”, pg. 5 & Figure 2).
It would have been first obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to employ Tindal, Govind, Saxl, and Gamble’s method of using a microfluidic device in order to determine the concentration of a substrate by constructing a calibration curve, as taught by Kostov. One would have been motivated to do so because Kostov teaches that the calibration curve can be constructed to determine the amount of binding between glucose and glucose binding protein, as well the concentration of glucose in a sample via fluorescent measurements (see, e.g., Kostov, “Calibration”, pg. 6). Moreover, Kostov teaches that over-labelling or under-labelling the molecules will affect the calibration curve and the fluorescence readouts (see, e.g., Kostov, “Fluorometer design and operation”, pg. 8); therefore, one of ordinary skill in the art would understand that constructing the calibration curve would also ensure that molecules are labelled correctly. Furthermore, Govind and Saxl teach the measurement of glucose concentrations by via fluorescent read-outs of glucose binding to glucose binding protein within a microfluidic device (see, e.g., Saxl, Figures 2-3) (see, e.g., Govind, [009], [0015]). Therefore, based on the teachings of Tindal, Govind, Saxl, Gamble and Kostov, it would have been obvious to construct a calibration curve when measuring glucose binding to glucose binding protein because this would allow for one to accurately calculate the concentration of glucose in a sample by measuring fluorescence.
It would have been secondly obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use Tindal, Govind, Saxl, and Gamble’s microfluidic device to determine the concentration of a substrate, wherein the microfluidic device contains a microfluorometer, as taught by Kostov. One would have been motivated to do so because Kostov teaches that using a microfluorometer system is a promising tool for accurate measurements of low glucose concentrations in biological samples (see, e.g., Kostov, Conclusion, pg. 9). Moreover, Kostov teaches that using a microfluorometer allows for the production of a handheld glucose detection system that can measure the amount of glucose in a sample using fluorescence via glucose binding to glucose binding protein (see, e.g., Kostov, “Theory of Operation”, pgs. 2-3 & “Microfluorometer system”, pg. 4). Furthermore, Govind and Saxl teach the measurement of glucose concentrations by via fluorescent read-outs of glucose binding to glucose binding protein within a microfluidic device (see, e.g., Saxl, Figures 2-3) (see, e.g., Govind, [009], [0015]). Therefore, based on the teachings of Tindal, Govind, Saxl, Gamble and Kostov, it would have been obvious to construct a microfluidic device to measure glucose concentrations in a sample, wherein the microfluidic device contains a microfluorometer because the microfluorometer allows for detection of low glucose concentrations in a biological sample via fluorescent readouts resulting from glucose binding to glucose binding protein, and allows for the device to be handheld.
It would have been thirdly obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use Tindal, Govind, Saxl, and Gamble’s microfluidic device to measure the concentration of a substrate, wherein the microfluidic device requires the column to be flush with the microfluorometer, as taught by Kostov. One would have been motivated to do so because Kostov teaches that the labelled glucose binding protein can be excited at a specific wavelength, and the emission can be detected at a specific wavelength (see, e.g., Kostov, “Optics”, pgs. 4-5); therefore, “sandwiching” the cuvette between photodiodes allows for the photodiodes to select for the emission wavelengths that are emitted from excitation of the glucose binding protein within the sample (see, e.g., Kostov, “Optics”, pgs. 4-5); thereby acting as a detector for the microfluorometer (see, e.g., Kostov, “Fluorometer design and operation”, pg. 7). Additionally, based on the teachings of Kostov’s handheld glucose monitoring device (see, e.g., Kostov, “Theory of Operation”, pgs. 2-3 & “Microfluorometer system”, pg. 4), one of ordinary skill in the art would understand that placing the microfluidic device flush with the microfluorometer would allow for the production of a smaller device for measuring glucose concentrations in a sample. Furthermore, Govind and Saxl teach the measurement of glucose concentrations by via fluorescent read-outs of glucose binding to glucose binding protein within a microfluidic device, also known as a factory-on-a-chip microfluidic device, which is small in scale (see, e.g., Saxl, Figures 2-3) (see, e.g., Govind, [009], [0015]). Therefore, based on the teachings of Tindal, Govind, Saxl, Gamble and Kostov, it would have been obvious to produce a microfluidic device for measuring glucose concentrations, wherein the microfluidic device is flush with the microfluorometer because this allows for the photodiodes within the microfluorometer to detect the emission wavelengths emitted from the glucose binding proteins. One would have expected success because Tindal, Govind, Saxl, Gamble and Kostov all teach methods of fluid processing. Additionally, Tindal, Govind, Saxl, and Kostov all teach methods of processing glucose samples to measure glucose concentration(s) within samples.
Examiner’s Response to Arguments
Regarding Applicant’s arguments that Govind and Saxl do not teach amended independent claim 10 (remarks, pages 6-8), as discussed above, all previous 35 U.S.C. 103 rejection have been withdrawn; however, new grounds of rejection are set forth above. Govind and Saxl were not relied upon in the above presented rejection to teach the newly presented claim limitations; therefore, Applicant’s arguments are moot.
Regarding Applicant’s arguments pertaining to the teachings of Ge for claims 12 and 23 (remarks, pages 9-10), Ge was not relied upon in the rejection presented above; therefore, Applicant’s arguments are moot.
Regarding Applicant’s arguments pertaining to Gamble and the second valve downstream of the aseptic sampling device (remarks, pages 10-11), this argument is not persuasive because Gamble teaches method of fluid processing wherein a sample source (see, e.g., Gamble, Figure 2, Sample Source 40), which one of ordinary skill in the art would recognize can be a sample tube, is positioned upstream of a column with a first rotary valve positioned in between (see, e.g., Gamble, Figure 2). Additionally, Gamble teaches that the rotary valve can be controlled to inject a predetermined about of sample from the sample source into the column (see, e.g., Gamble, pg. 31, col. 3, lines 37-40). One of ordinary skill in the art would have been motivated to have a valve positioned before the microfluidic column in so that the valve can inject a predetermined amount of sample and wherein the valve can be opened and closed in order to prohibit entry or allow entry of the substrate-containing buffer into the column.
Conclusion
Claims 10-17, 20-25, 27-28, and 31-33 are rejected.
No claims are allowed.
Correspondence Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NATALIE IANNUZO whose telephone number is (703)756-5559. The examiner can normally be reached Mon - Fri: 8:30-6:00 EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sharmila Landau can be reached at (571) 272-0614. 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.
/NATALIE IANNUZO/Examiner, Art Unit 1653
/SHARMILA G LANDAU/Supervisory Patent Examiner, Art Unit 1653
