The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
For examination purposes, claim 43 is being treated as follows. A system for determining a concentration of acetone in breath comprising a mouthpiece, a sensor in fluid communication with the mouthpiece or in fluid communication with an intermediate breath storage device that is in fluid communication with the mouthpiece; the sensor comprising a hydroxylamine salt and a volume of a liquid sorbed onto a sorbent material at a plurality of detection positions and configured to generate a spatially differential pH response in a property of the sensor to an identical acetone concentration at the different detection positions by varying the concentration of the hydroxylamine salt at the different detection positions; a detector to measure the differential pH response; and a processor to calculate the acetone concentration; wherein the volume of liquid is from 0.005 mL to 1 mL.
Claims 58 and 62-63 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. Claims 58 and 62 are directed to a limitation that is either currently in the independent claim from which they depend or have a limitation which is of a scope that is greater than a similar limitation in the independent claim from which they depend. Thus it is int clear what further limitation these claims are directed toward. In claim 63, “the step of breathing through the mouthpiece” does not have proper antecedent basis in claim 53.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 58 and 62 are rejected under 35 U.S.C. 112(d), as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. With respect to claim 58, claim 53 already requires the liquid volume to be from 0.005 mL to 1 mL so that claim 58 is of a scope that is attempting to increase the scope already required by claim 63. With respect to claim 62, claim 43 already require the language of claim 62 such that the language of claim 62 does not provide a further limitation of claim 43. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 43, 45-49, 53-58 and 62-63 are rejected under 35 U.S.C. 103 as being unpatentable over Montagnino (US 2002/0143267) in view of Moore (US 5,332,548) and Bikulov (SU 728083), Kravchenko (SU 958930), Derkach (SU 1109640) or Pryor (JP 63-75561) and further in view of Tao (US 2019/0094146), Landini (US 2009/0196796) and Atkin (US 2009/0290161) or Satterfield (US 2014/0276100). With respect to claim 43, In the patent publication Montagnino teaches a metabolic fitness training apparatus which measures the concentration of acetone in a trainer's breath while exercising. The metabolic fitness training apparatus include a housing (25), an acetone sensitive sensor (23), an optical detection circuit (34, figure 10), and a mouthpiece (24) attached to the housing. The sensor contains reagents such as salicylaldehyde or derivatives thereof which react with acetone to change the optical transparency of the sensor. The optical detection circuit may include an LED (33) and a photodetector or a photometric instrument (32) to measure the change in optical transparency of the sensor, and convert that change to acetone concentration. There may also be a display (26) for viewing the acetone concentration. Paragraph [0042] teaches that the loss of cell sensitivity (i.e., optical absorbance change vs. acetone exposure) may be correlated with the mass loss of sensing materials, indicating that the key mechanism is the loss of volatiles such as water and salicylaldehyde molecules. Thus, proper amounts of molecular encapsulant materials (such as cyclodextrins) may be added to the formulation to enhance moisture and salicylaldehyde retention without degrading the desired response. Paragraph [0043] teaches that to measure the concentration of breath acetone, the sensor is placed in the optical path of an LED/photodetector circuit. As acetone reacts with the reagents on the sensor, the optical transparency of the sensor is decreased and thus, so is the output of the photodetector. The rate of change in cell absorbance (A) is then calculated and converted to acetone concentration. Thus, the acetone sensitive sensor acts as a dynamic optical filter of the LED output, exhibiting a defined linear relationship between the rate of change in absorbance and its acetone exposure. Paragraphs [0044]-[0046] describe the how the device would be used to measure acetone in the breath of one who is exercising. With respect to claim 43, Montagnino does not teach a colorimetric sensor including a liquid and different concentrations of a hydroxylamine salt at different positions of the sensor configured to generate a differential positional response to a constant concentration of acetone that is responsive to a pH of the liquid, and intermediate storage device in fluid communication with the mouthpiece, a processor configured to calculate the concentration of the acetone in the fluid from the change in the variable or a specific amount of liquid sorbed on the sensor.
Moore teaches a sensor for sensing a concentration of acetone in a fluid (see at least column 1, lines 6-50, detecting a gaseous volatile analyte that includes formaldehyde or a derivative thereof and ketones; column 3, lines 4-18 describing tests for acetone including one having hydroxylamine hydrochloride and Bromophenol Blue; and column 7, lines 40-47 teaching that although the invention is described with particular reference to detecting or determining formaldehyde emissions, it should be understood that the invention is also applicable to other gaseous or volatile analytes including acetone), the sensor configured to generate a differential response to a constant concentration of acetone (figure 3 and its associated description in column 11, line 65 to column 12, line 60; see also column 6, lines 4-29; and column 9, lines 18-44, a concentration gradient is desired for a more quantitative reading with a substrate having two or more test regions, a uniform concentration of the reagent is applied to each region and the concentration varies between regions), wherein the sensor comprises a hydroxylammonium salt (column 9, lines 18-44, a particularly suitable analyte-reactive component is hydroxylamine phosphate; for acetone emissions, a suitable analyte-reactive component includes, for example, hydroxylamine hydrochloride; instant paragraph [00031] teaches both hydroxylammonium chloride and hydroxylammonium phosphate as the hydroxylammonium salt), and whereby exposure of the fluid to the hydroxylammonium salt in the presence of a volume of a liquid produces a change in a variable, said variable being dependent upon the pH of the liquid (see at least column 10, lines 1-53; three moles of formaldehyde are required to react stepwise prior to the release one mole of the acid according to the equations provided); wherein the differential response is spatially differential, whereby the sensor is configured to respond to the acetone at a plurality of detection positions on the sensor, said detection positions having different sensitivities to the acetone; and the differential sensitivity to acetone on the sensor is produced by a varying concentration or amount of the hydroxylammonium salt at different positions of the sensor (see at least column 10, lines 1-53; if the substrate is provided with a concentration gradient, then the region of the gradient with the lowest concentration of hydroxylamine phosphate turns yellow first in the presence of a given amount of formaldehyde per surface area unit, and those regions of higher concentration turn yellow more slowly, with the region of highest concentration changing to yellow last). Column 3, lines 4-18 teach that tests strips comprising an inert substrate or carrier, such as paper or film, and impregnated with testing reagents that produce a visible color change are well known in the art. Soviet Union Patent 0728083 discloses a strip indicator for determining acetone in air using moist tape impregnated with hydroxylamine hydrochloride and Bromophenol Blue, and assessed by photocolorimetry. Column 5, lines 1-13 teach that the substrate comprises a planar strip formed of a material which is substantially inert to the analyte, and further is capable of holding, containing, sorbing, or otherwise being impressed with or impregnated with the reagents comprising the test field. Suitable materials include papers, fabrics, and films, which can be cellulosic or synthetic, including nonwovens, or a combination thereof. Alternatively, the substrate may comprise a particulate or filament, such as alumina, glass fiber, glass beads, silica gel, or molecular sieves, which may be sorbent, and typically applied as a coating or thin layer on an inert carrier. Column 9, line 45 to column 10 lines 53 teaches that an indicator, sometimes referred to as the second reactant, is incorporated into the test field of the substrate to provide a color signal, and the choice depends largely on the analyte and analyte-reactive component. The particular color signal is preselected, and preferably is in the visual range, but may be in the UV range. The indicator typically is applied to the substrate as a solution, which may be either aqueous or organic, depending on the composition of the indicator. It is desirable to apply the analyte-reactive component to the substrate first and after adequate drying, the indicator is applied. Suitable indicators for use in conjunction with hydroxylamine phosphate include, for example Bromophenol Blue, methyl orange or Bromcresol Green. Example 1 in columns 14-15 teaches a detector along with a method for calculating the concentration directly from the detector. Moore does not teach a processor configured to calculate the concentration of the acetone in the fluid from the change in the variable, an amount of liquid sorbed on the sorbent or a mouthpiece to introduce breath into the system.
In the patent document Bikulov was cited by Moore and teaches the quantitative determination of atmospheric acetone concentration (e.g. in permissible concentration monitoring) by hydroxylamine-HCl (I) and Bromophenol blue indicator gives increased sensitivity by exposing moist tape impregnated with the reagents to the atmosphere. The woven tape is impregnated with a solution containing. (%): (I) 0.15-0.25; indicator 0.8-1.2, and dried. Prior to use, the tape is moistened with solution containing (%):(I) 0.25-3; indicator 0.1-0.15, treated with gas for analysis and assessed by photocolorimetry.
In the patent document Kravchenko teaches the determination of Me2CO (acetone) consists of blowing air sample onto a cloth indicator sheet treated with a solution of bromophenol blue and NH2OH.HCl (hydroxylammonium hydrochloride), followed by colorimetric measurement. The sensitivity and precision of the method are increased, by using a cloth indicator ribbon treated with a solution that also contains 4-5% Na2S203 and CaCl2 (sodium thiosulphate and calcium chloride). The vol. ratio of bromo-phenol blue:NH2OH.HCl: Na2S203:CaCl2 is 1:(4-4.5): (0.45-0.7):(0.3-0.35).
In the patent document Derkach teaches the determination of Me2CO (acetone) in air. The determination involves passing the sample through silica-gel saturated with a hydroxylamine hydrochloride solution and methanyl yellow indicator, and measuring the length of formed colored layer. The method uses silica-gel KSKG, which is impregnated with a 1% alcoholic solution of hydroxylamine hydrochloride and a 0.1% solution of aqueous methanyl yellow. It is prepared by stirring 10g of silica-gel with 8ml of hydroxylamine hydrochloride until a friable state is obtained followed by addition of 1 ml of the indicator solution and drying in air. It is filled in glass tubes with 2.3-0.1 mm diameter and secured in position with an air permeable tampon. Acid vapors are removed from the air by means of an absorbing cartridge, comprising silica-gel impregnated with a solution of sodium carbonate and methyl orange. The position of the cartridge is also secured by tampons. 280 cm3 of air is passed through the tube and a length of discolored silica-gel column is measured. The method allows the control of acetone present in air in concentration less than 2 microg/m to power 3. The sensitivity is 3 times greater than in method which used bromophenol blue as the indicator.
In the patent document Pryor teaches a medium comprising an inert particulate material carrying a first compound (I hydroxylamine hydrochloride) selectively reacting with breath acetone to release an acid and a second compound (II, thymol blue) undergoing a visually detectable color change in response to a lowering of the pH. The indicator medium is useful for the simple and convenient determination of acetone at 0-60 ppm in the breath. The determination is especially used with diabetic patients to control the sufficiency of insulin dosages. Subjects on rigorous diets may need monitoring of blood and urine for acetone levels qualitatively and quantitatively. In an example intermediate density silica gel of 8-12 US mesh size was activated in vacuo under N2, then NH2OH.HCl (0.0067g/g silica gel), thymol blue (1.48 g/g silica gel; used in dilute aqueous NaOH solution).
In the patent publication Landini teaches a mouthpiece for use with an electronic analyzer for breath analyte detection in an individual. The mouthpiece includes a biosensor and a hydration system. The biosensor includes a chemically active area where a chemical reaction takes place and the hydration system delivers a liquid to the chemically active area of the biosensor to at least one of enhance, enable, and facilitate the chemical reaction. The mouthpiece further includes hardware to transmit breath analyte data. Paragraph [0003] describes some conventional mouthpieces used for vapor analysis (e.g., breath analyte analysis) and teaches that the particular breath collection method requires multiple components. For example, a user exhales into the mouthpiece, a condenser removes breath moisture, and an attached container is used to trap a final breath sample. An analyte biosensor is used for subsequent analyte analysis. The analyte biosensor is either located within the attached container or in a separate piece of analysis equipment that obtains a breath sample from the container. The analyte biosensor chemically reacts with the one or more analytes in the breath sample. The presence of a reaction signifies the presence of the specific analytes, and the strength of the reaction can signify the amount of analyte in the breath sample. The amount of moisture removed from the condenser can be inconsistent and variations due to different mammalian moisture content in the breath can alter the speed and/or strength of the reaction on the analyte biosensor. As none of these mouthpieces incorporate any type of hydration system to create an environment with consistent moisture content for each reaction, results may be inaccurate. Figure 1 illustrates a mouthpiece (10) made of a polymer material, such as polyethylene that is connected to an electronic analyzer (100). The mouthpiece can include an integrated biosensor (11), an inlet (12), an outlet (13), and electrical connectors (14) to connect to an electrical connector receptacle (101) on the electronic analyzer. The mouthpiece with the integrated biosensor can be used for the direct detection of breath analytes such as acetone. The biosensor can include a chemically-active area, such as an area including an enzyme, to permit a chemical reaction when in contact with the analyte. During use, an individual can exhale through the inlet, causing breath gasses to flow directly over the biosensor resulting in a reaction on the biosensor and out through the outlet. Paragraph [0016] teaches that the biosensor can require a hydration material in order to enable, facilitate, and/or enhance the enzymatic reaction because variations due to different mammalian moisture content in the breath can alter the speed and/or strength of the reaction. To help provide accurate results with improved precision, the mouthpiece 10 can include an integrated hydration system capable of providing a consistent amount of hydration material to the biosensor prior to each reaction. The hydration material can be water, an acid, a base, a neutral buffer, a hydrogel, a salt solution, or a liquid containing polymers depending on the type of biosensor. Paragraph [0018] describes a manually actuated reservoir-based hydration system shown in figure 2, including a wetting port (21, a small hole in the mouthpiece above the biosensor of a size suitable to allow clearance of a syringe or pipette tip). A syringe or pipette can be used to manually wet the biosensor prior to analysis with volume range of hydration material from about 0.05 micro-liters to about 100 micro-liters. Figure 3 illustrates another manually activated hydration process in which the mouthpiece includes a fluid-filled sack (31, also known as a blister pack) housed within the mouthpiece near the biosensor or integrated onto the sensor strip of the biosensor. A pin (32), syringe, or roller can be used to manually pierce or puncture the sack to hydrate the active area of the biosensor. In other embodiments, a pushbutton (not shown) on the mouthpiece can include a piercing pin to pierce the sack when the pushbutton is depressed. The pin or roller can also be housed within the mouthpiece and can be depressed to pierce the sack remotely by the electronic analyzer or another electronic device to which the mouthpiece is electrically connected. Figures 4A-4B illustrate a semi-automatic hydration process in which a mouthpiece including a hydration tube (41) and a plunger (42) such that coupling the mouthpiece to the electronic analyzer causes the plunger to be depressed (task 44)to release hydration material within the hydration tube to hydrate the active area of the biosensor (task 45). A signal can then be produced by the biosensor 11 based on the chemical reaction with an analyte (task 46). The signal can then be transmitted to the electronic analyzer through the electrical connectors. Finally, data interpreted from the signal can be displayed, stored, or transmitted by the electronic analyzer (task 47). In some embodiments, the hydration process can be fully automated so that hydration occurs with no user intervention. As illustrated in figure 5, a mouthpiece can have two separate connections to the electronic analyzer, including the electrical connectors and a pump line (51) that terminates above, below or at some distance from the active area of the biosensor. In addition, the electronic analyzer can include an integrated pump (102) coupled to the pump line. Prior to analysis, the electronic analyzer can automatically perform the hydration process by supplying liquid from the pump through the pump line 51 to hydrate the active area of the biosensor. Paragraphs [0021]-[0024] teach how the automated hydration system functions as well as giving other possible components that can be included in the hydration system.
In the patent publication Tao teaches a micro-colorimetric sensor for sensing target chemicals that converts time sequence information into a spatial distribution of color. By tracking the spatial color distribution, chemical exposure over time is thus detected, which overcomes the limitation of traditional colorimetric sensors. A porous media is coated on a top surface of the substrate. Multiple sensing chemicals are fused in parallel linear channels into the porous media coating. A plate is affixed over the substrate top surface to cover the plurality of parallel linear channels. An air sample is diffused along the porous media to get a clear pattern of spatial color distribution and color images are captured. Optical parameters like gradient of spatial color distribution, intensity, and absorbance, etc., can be tracked to calculate analytes concentrations. Paragraph [0044] describes one example of a micro-colorimetric sensor array for detection of Nitrogen Dioxide, Ozone, and Formaldehyde fabricated by an inkjet printing method. Silica gel was used as porous media and coated on a polyester substrate. Three sensing solutions containing N,N-dimethyl-1-naphthylamine, indigo carmine, and hydroxylamine sulfate (a hydroxylammonium salt) respectively were prepared for selective detection of nitrogen dioxide, ozone, and formaldehyde. The three sensing solutions were inkjet printed on the porous silica gel layer in the form of three parallel lines. An acrylic plate was then affixed over the top surface of the porous silica layer to cover the three parallel linear channels. Figure 10 shows top views of the sensor array after exposing to ozone, nitrogen dioxide, and formaldehyde. Each sensing channel changed color and a clear color gradient was generated after exposing to the corresponding analyte, and there is no obvious cross talking between different sensing channels. Paragraph [0052] teaches that the test results of traditional colorimetric sensors such as detector tubes usually read by naked-eye. This method is not accurate and not adequate for a micro-colorimetric sensor. To overcome this difficulty, a sensitive CMOS imager was used in the device to obtain high quality images and fundamentally improve the sensitivity and detection limit. To further improve the sensitivity, an optical edge tracking technique has been developed. Several optical edge tracking methods have been reported to highly improve the detection limit (the detector and processor, also see figures 5-8 with their associated discussion). Paragraph [0040] teaches that each of the sensing chemicals is selected for a particular target chemical, so that the sensor can simultaneously detect multiple chemicals. Air sample diffuses passively along each linear channel without using a pump, and the target chemical in the air sample reacts with the sensing chemical in the linear channel, starting from the inlet, which creates a color gradient that moves from the inlet towards to the channel end. Because air diffusion in the porous media is substantially slower than that in air, the color gradient is sharp and moves slowly along the linear channel, which prolongs the lifetime of the sensor, and allows continuous monitoring of chemicals over a long time. Rates of diffusion and reaction can be controlled by predetermined porous media and its porosity, and amount of sensing chemicals loaded, so that barriers between channels are not always necessary to prevent fast diffusion from the channel sideway. The slowly moving color gradient associated with passive diffusion creates a challenge to accurately track the moving color gradient. This difficulty is overcome by introducing a color gradient tracking imaging processing algorithm, which can track the moving speed of the color gradient in each linear channel. The moving speed of the color gradient reflects the concentration of the target chemical. Other optical parameters like intensity and absorbance, etc., can also be used to calculate analytes concentrations. In other examples, the tracking imaging processing algorithm is selected from the group consisting of tracking intensity or absorbance change of the whole or part of the image, tracking the moving of intensity or absorbance pattern of the whole or part of the image where the pattern includes point, corner, edge, and block and combinations thereof. Paragraph [0073] teaches that several publications are incorporated herein in their entirety by this reference. In particular paragraph [0081] lists a reference directed to selective diagnosis of diabetes using a sensing layer for acetone in exhaled breath.
In the patent publication Atkin teaches a device, system, and method for measuring acetone levels exhaled from a patient and correlating the measured level to a blood glucose concentration. Paragraphs [0007]-[0012] discuss/teach that it is known that a larger quantity of acetone vapors contained in exhaled air of diabetics, pregnant women, people engaged in heavy physical labor, athletes at high physical loads. It is also known that the concentration of acetone in exhaled air correlates with the content of glucose in the blood. In other words, the acetone is a reliable biological marker for monitoring the content of glucose in the blood that allows control of glucose in the blood. Paragraphs [0013]-[0016] describe various devices for noninvasively determining of the glucose content in the blood of people with diabetes and their disadvantages. Paragraphs [0017]-[0029] provide a brief description of the handheld portable device, which will determine the concentration of acetone in exhaled air with a minimum content of acetone 3-5 mg/liter with an accuracy that will satisfy doctors and patients. The device includes a) an inlet for expirated air (12, equivalent to a mouthpiece); b) a dosator (11) for receiving air from said inlet; c) an actuator (21) for filling said dosator with substantially the same volume for each measurement, said actuator interrupts air from said inlet when said dosator reaches a specified volume; d) a chemical cell containing a chemical cell solution (14,23); e) a light source constructed and arranged for emitting light to pass through and spectrally analyze said chemical cell solution (25); e) an optical sensor (17); and f) a microprocessor which produces an output correlating measurements of said optical sensor with blood glucose concentration. Paragraphs [0030]-[0035] describe a method for determining acetone concentration in exhaled air and correlating said acetone concentration with blood glucose levels, the method including the following steps: a) providing the device; b) initiating a blank reading spectral of said chemical sensor solution; c) instructing a user to inhale and hold their breath for about 3-5 seconds; d) having the user exhale into an inlet (mouthpiece) of said device; and e) taking a spectral reading of the chemical cell solution after reaction with acetone in expired air; the device measures the change in absorbance from said blank reading with said spectral reading after reaction of said chemical cell solution with acetone from expired air and said device produces an output whereby said difference in absorbance is correlated with blood glucose concentration of said user. Paragraph [0060] teaches that the dosator is a bellow or balloon type structure (intermediate storage device) that is filled to a fixed volume. Once the dosator is filled, an actuated distributor 21 closes a valve to restrict any additional air from entering the dosator and a valve is opened by the system that automatically sends the air through an air tube (27) to interact with a chemical sensor solution 28 in chemical sensor cell 23.
In the patent publication, Satterfield teaches a system for sensing an analyte in a breath sample. The system includes a breath bag, a cartridge and a base. The breath bag contains the breath sample (in intermediate storage device). The bag includes a mouthpiece fixedly disposed on the breath bag (see at least figures 2-3 and their associated discussion). The cartridge includes an interactant that reacts with the analyte and generates a change in an optical characteristic relative to a reference (see at least figure 4-5 and 9). The base includes a flow path, a breath bag receiver for detachably receiving and retaining the mouthpiece of the breath bag in fluid communication with the flow path, and a cartridge receiver that detachably receives and retains the cartridge in the base, such that the base engages the cartridge so that the interactant is in fluid communication with the flow path. The base further includes a flow handling system in fluid communication with the flow path, an optical subsystem for sensing the change in the optical characteristic, a processor operatively coupled to the flow handling system and the optical subsystem, and a user interface operatively coupled to the processor and comprising a start command (see at least figures 8-9 with their associated discussion). Upon user selection of the start command, the processor is configured to automatically regulate the flow handling system to move the breath sample in the flow path and to contact the breath sample and the interactant. Upon the occurrence of a predetermined process parameter, the processor is configured to automatically regulate the optical subsystem to sense the change in the optical characteristic, to correlate the sensing of the optical system with information about the analyte in the breath sample, and to output the information about the analyte in the breath sample to the user interface. Related methods also are provided.
With respect to claim 43, it would have been obvious to one of ordinary skill in the art at the time the application was filed to use the hydroxylammonium chloride/hydroxylamine hydrochloride reagents of Moore, Bikulov, Kravchenko, Derkach or Pryor in the Montagnino device because Moore includes a hydroxylamine reagent for an aldehyde, teaches that other analytes can be measured, specifically teaches hydroxylamine hydrochloride for testing of acetone (column 9, lines 40-44) and discussed the Bikulov reference for detection of acetone and each of Bikulov, Kravchenko, Derkach and Pryor is directed to measurement of acetone with a hydroxylammonium chloride/hydroxylamine hydrochloride reagent in a manner similar to Montagnino. With respect to, the hydroxylammonium salt and indicator being sorbed into a sorbent and the volume of liquid, Montagnino is concerned with the loss of water on the functioning of the sensor and Bikulov and Landini teach hydrating/moistening the detector prior to use. All of these references would have left a presence of liquid in the sensor. Landini teaches a volume of liquid that covers a majority of the range being claimed. Thus the limitation is met within the confines of the claim scope and the teachings of the at least these references. Additionally, with respect to claim 43, it would have been obvious to those of ordinary skill in the art at the time the application was filed to use a detector with a processor such as taught by Landini or Tao to calculate the concentration based on the detected response because Montagnino has a structure that is used to calculate the measured acetone concentration in breath using a colorimetric sensing composition/sensor and at least Tao shows that such calculation can be performed simply and easily with a detector connected to a processor. Further, it would have been obvious to one of ordinary skill in the art at the time the application was filed to incorporate a hydration system as taught by Landini into the Montagnino apparatus used for measuring acetone in a breath sample because there is a need to take steps to insure that there is a proper amount of moisture present for the a colorimetric sensing composition to function properly as taught by Montagnino, the Bikulov reference teaches that the reagent was present as a moist indicator and as taught by Landini if one relies on the moisture in the breath sample there are possible inaccuracies that could occur because of differences in the amount of moisture in a typical breath sample. Finally, Atkins and Satterfield teach different forms of intermediate storage devices connected to a mouthpiece in a breath analyzer that store the breath sample for analysis by the sensor. Thus it would have been obvious to one of ordinary skill in the art at the time the application was filed to modify the Montagnino device with an intermediate storage device connected to the mouthpiece as taught by either Atkins or Satterfield because of the ability to provide a known constant volume of breath for analysis as taught by Atkins or to be able to collect the breath separately from the analysis as taught by Satterfield.
With respect to claim 45, figure 10 of Montagnino show and/or teaches that the sensor is placed in a flow channel or an analysis chamber.
With respect to claim 46, the variable of Montagnino is absorbance and the senor comprises a sorbent material with the colorimetric indicator sorbed thereon. The final paragraph of column 9 in Moore teaches the presence of an indicator or second reactant to provide a color signal. The first paragraph of column 10 of Moore teaches that the indicators include bromophenol blue, methyl orange or bromocresol green all of which are claimed as halochromic indicators in instant claim 48. The indicator compositions of Bikulov, Kravchenko, Derkach and Pryor include both the hydroxylammonium salt and a halochromic indicator on a sorbent material such that modification of Montagnino with the acetone sensing compositions of Moore, Bikulov, Kravchenko, Derkach and Pryor shows the obviousness of claim 46 for the same reasons given for claim 43 above.
With respect to claim 47, at least the Pryor composition included a weak base in the composition so that modification of Montagnino with the acetone sensing composition of at least Pryor shows the obviousness of claim 47 for the same reasons given for claim 43 above.
With respect to claim 48, the compositions of Moore, Bikulov, Kravchenko, Derkach and Pryor include at least one halochromic indicator from those listed in claim 48 so that modification of Montagnino with the acetone sensing compositions of Bikulov, Kravchenko, Derkach and Pryor shows the obviousness of claim 48 for the same reasons given for claim 43 above.
With respect to claim 49, each of Moore, Tao, Bikulov, Kravchenko, Derkach and Pryor teach the hydroxylammonium salt as hydroxylammonium chloride/hydroxylamine hydrochloride so that modification of Montagnino with the acetone sensing compositions of Bikulov, Kravchenko, Derkach and Pryor shows the obviousness of claim 49 for the same reasons given for claim 43 above.
With respect to claim 62, the language/requirement of the claim is incorporated into claim 43 and has been addressed above with respect to that claim.
With respect to claims 53-57, Montagnino teaches various methods in which the system and the sensor of claim 43 are exposed to a sample. The utilization of the modified system and sensor of Montagnino in view of Landini and Tao and further in view of Moore, Bikulov, Kravchenko, Derkach or Pryor would include the steps of independent claim 53 so that the method of claim 53 is obvious for the reasons given above for claim 43. Claims 55-56 are respectively similar to claims 46-47 so that they are obvious for the reasons given above for claims 46-47.
With respect to claims 54 and 57, Moore teaches a variety of ways that the differential response can be obtained including at least one of the claimed possibilities.
With respect to claim 63, modification of the device used in the Moore method as described above for claim 62, would have covered the method of claim 63 so that claim 63 is obvious for the reasons given above for claim 62.
Claims 60-61 are rejected under 35 U.S.C. 103 as being unpatentable over Moore in view of Landini and Atkins, Montagnino or Satterfield, further in view of Tao or Theil and finally in view of Bikulov, Kravchenko, Derkach or Pryor as applied to claim 53 above, and finally in view of Choi (Analytical Chemistry 2013). Tao incorporates a reference authored by Choi (see paragraph [0081]) relative to diagnosis of diabetes through sensing acetone in exhaled breath. Montagnino does not teach any details on a method of doing that.
The Choi paper is the paper incorporated by reference in Tao relative to diagnosis of diabetes through sensing acetone in exhaled breath. The first two paragraphs of the paper on page 1792 teach that there are hundreds of species of volatile organic compounds (VOCs) in human breath; these compounds are exhaled from the blood through breath in the lungs. The exact evaluation of the concentration of these VOC gases offers useful information that can be used to identify biomarkers for analyzing the human body condition. Disease diagnosis using exhaled breath has attracted much attention because of its key advantages in terms of noninvasive and real-time diagnosis. So far, gas chromatography/mass spectrometry (GC/MS) and the optical spectroscopy method have been widely used for breath analysis for potential detection of lung cancer, diabetes, heart disease, malnutrition, kidney disorders and asthma. However, these techniques are limited for applications in portable sensing devices owing to the bulky equipment size and complexity in measurement. To achieve accurate disease diagnosis using exhaled breath sensors, the minimum detection limit should be in the range of ppb (parts per billion) level, particularly in highly humid atmospheres. In addition, selective detection should be guaranteed to confirm exact recognition of a specific disease. For example, in the case of diabetes diagnosis, an acetone concentration of 300−900 ppb in exhaled breath should be measurable because the acetone concentration increases from 300 to 900 ppb for healthy humans to 1800 ppb for diabetes patients.
With respect to claims 60-61, it would have been obvious to one of ordinary skill in the art at the time the application was filed to use the modified device and method of Montagnino with the range taught by Choi to distinguish between healthy individuals and diabetes patients to determine whether the measured value of acetone in the exhaled breath indicated that an individual has diabetes or needs to have a treatment plan modified because at least Pryor indicates that acetone in breath can be used for diabetic patients to control the sufficiency of insulin dosages and Choi gives ranges that constitute healthy and diabetic individuals.
Applicant's arguments filed July 11, 2025 have been fully considered but they are not persuasive. In response to applicant’s response, new rejections under 35 U.S.C. 112(b) and 35 U.S.C. 112(d) have been applied to certain claims and the obviousness rejections have been substantially modified by using the previously applied Montagnino reference as the primary reference. As a result arguments directed toward the new rejections are moot.
With respect to the obviousness rejection, and in particular to the argument that the primary reference Moore is directed to sensing emissions from a solid material, examiner notes that Moore is no longer being applied as the primary reference. As such any arguments directed toward Moore as the primary reference and its modification by the previously applied secondary reference are not commensurate in scope with the instant claims. This applied to the bulk of applicant’s arguments in the response. Thus they are moot and/or not persuasive with respect to the current obviousness rejections. Examiner notes that Moore cited a breath acetone sensing reference as prior art and clearly teaches the sensing of acetone with a sensing composition similar to that described by Bikulov for sensing breath acetone (see column 9, lines 41-44). This shows that while Moore is directed toward a specific application (measurement of volatiles in a “source specific” manner rather than detecting a volatile or gaseous analyte in ambient or atmospheric air that could have originated from any source; see column 4, lines 18-22 and the paragraph bridging columns 6-7), those of ordinary skill in that art would have been aware of the use of the sensing composition taught by Moore for breath acetone and would have understood that the sensing composition, its configuration and the associated methods of use are appropriate for teaching how to modify a colorimetric acetone sensing composition so that it can be used to make quantitative measurements. Relative to applicant’s urging that none of the documents cited by examiner disclose, suggest, teach or even hint at the system or method presently claimed in the instant application. This argument appears to be an argument that would be directed toward references individually applied against the claims rather than in an obviousness combination as currently applied against the claims. Thus the argument is not persuasive because it is not commensurate in scope with the current obviousness rejections.
For these reasons, applicant’s arguments are not persuasive.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. The additionally cited art is related to detection devices for breath and/or colorimetric sensor structures used to measure an analyte. Of note are the Schwab (US 2,785,057) and Rakow references. Schwab teaches a structure in figures 20-21 that a plurality of reagent masses with a varied amount of reagent in the respective masses to provide a quantitative indication by the relative darkening or failure to darken of the respective reagent masses. Rakow teaches methods and devices for detecting the presence of an analyte which may utilize an array of at least two sensing elements that differ in their response to an analyte of interest. The methods include methods of making and using such arrays of sensing elements.
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/ARLEN SODERQUIST/ Primary Examiner, Art Unit 1797