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 .
Response to Amendment
The amendment filed 06/16/2026 has been entered. Applicant's amendments overcome the previous claim objections and 35 U.S.C. 112(b) rejections. Claims 1-19 remain pending.
Claim Rejections - 35 USC § 102
Claim(s) 1-5 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Zapol et al. (US 20180243527 A1), hereafter Zapol.
Regarding claim 1, Zapol discloses a nitric oxide generator (NO generation system of Fig. 1, par. 0184), comprising: an inlet (reactant gas intake 12; Fig. 1, par. 0184) arranged to receive a gas including nitrogen and oxygen (reactant gas can be atmospheric air/ambient air, par. 0015, 0183; atmospheric air has approximately 21% oxygen and 78% nitrogen by volume, par. 0381); an outlet (sample gas out near gas analysis sensor pack 54; Fig. 1); a pair of electrodes arranged downstream of the inlet (electrodes 24 downstream of reactant gas intake 12; Fig. 1) and configured to generate nitric oxide from the gas (electrodes 24 produce NO from the reactant gas; par. 0184); a pressure regulator configured to selectively adjust a pressure of the gas surrounding the pair of electrodes (feedback control maintains constant pressure in the spark chamber; par. 0680); an accumulator in communication with the pressure regulator (pump has feedback control; par. 0680), wherein the accumulator is configured to add volume to a flow path between the inlet and the outlet to store and maintain the pressure of the gas surrounding the pair electrodes as set by the pressure regulator (a feedback control on the pump maintains constant pressure in the spark chamber; par. 0680); a nitric oxide sensor (gas analysis sensor pack 54, Fig. 1) arranged to measure a concentration of nitric oxide downstream of the pair of electrodes (gas sensor chamber measures NO levels in the product gas, par. 0186); and a controller (treatment controller 30; Fig. 1) in communication with the pair of electrodes, the pressure regulator, and the nitric oxide sensor (Fig. 1 shows electrodes 24, pump 16, and nitric oxide sensor 54 are all in communication with the controller 30), wherein the controller is configured to selectively instruct the pressure regulator to adjust the pressure of the gas surrounding the pair of electrodes in response to the concentration of nitric oxide measured at the outlet by the nitric oxide sensor (controller controls electrodes and pressure within chamber surrounding electrodes through a feedback control on the pump to maintain constant pressure in the spark chamber to control NO generation; par. 0679-0681).
Regarding claim 2, Zapol discloses the nitric oxide generator of claim 1 (shown above), further comprising a scavenger (filter-scavenger-filter 38; Fig. 1) arranged upstream of the outlet and downstream of the pair of electrodes (filter-scavenger-filter 38 is upstream of sample gas outlet at 54 and downstream of electrodes 24; Fig. 1).
Regarding claim 3, Zapol discloses the nitric oxide generator of claim 1 (shown above), further comprising a filter arranged upstream of the outlet and downstream of the pair of electrodes (filter 50 is upstream of sample gas out at 54 and downstream of electrodes 24; Fig. 1).
Regarding claim 4, Zapol discloses the nitric oxide generator of claim 1 (shown above), wherein the controller is configured to instruct the pressure regulator to increase the pressure of the gas surrounding the pair of electrodes to increase the concentration of nitric oxide at the outlet (spark chamber pressure can be used as an input into the NO generation control algorithm, par. 0680; Zapol discloses lower pressure produces less NO in par. 0681 and high pressure produced more NO in par. 0385, and so it follows that to produce more NO, the spark chamber pressure would be increased; gas sensor data is used to automatically adjust NO production to match a target level, par. 0411; control algorithm input parameters include plasma chamber pressure which can be altered to adjust NO production rates, par. 0011, 0367, 0387).
Regarding claim 5, Zapol discloses the nitric oxide generator of claim 1 (shown above), wherein the controller is configured to instruct the pressure regulator to decrease the pressure of the gas surrounding the pair of electrodes to decrease the concentration of nitric oxide at the outlet (gas sensor data is used to automatically adjust NO production to match a target level, par. 0411; lower pressure in the plasma chamber leads to less NO production, par. 0681; control algorithm input parameters include plasma chamber pressure which can be altered to adjust NO production rates, par. 0011, 0367, 0387).
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
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.
Claim(s) 6 is/are rejected under 35 U.S.C. 103 as being unpatentable over Zapol.
Regarding claim 6, Zapol discloses the nitric oxide generator of claim 1 (shown above), wherein the controller is configured to selectively adjust a signal sent to the pair of electrodes (controller communicates with electrodes to control the concentration of NO in the product gas; par. 0184) to provide an inhaled concentration of nitric oxide between 50 ppm and 5000 ppm at the outlet (NO is present in concentration between 50-5000 ppm depending on the desired dose and inspiratory flow; par. 0484).
Zapol does not explicitly a nitric oxide concentration greater than or equal to about 150ppm.
However, it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to modify the concentration of Zapol from between 50 ppm and 5000 ppm to greater than or equal to about 150 ppm, as claimed, since the ranges overlap between 150 ppm and 5000 ppm and it has been held that “[i]n the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art' a prima facie case of obviousness exists”. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990).
Claim(s) 9-15, 18-19 is/are rejected under 35 U.S.C. 103 as being unpatentable over Zapol, in view of “Inhaled Nitric Oxide Explored for COVID-19 Oxygenation” by Ingrid Hein (article published May 13, 2020), hereafter Hein.
Regarding claim 9, Zapol discloses a nitric oxide generator (NO generation system of Fig. 1, par. 0184), comprising: an inlet (reactant gas intake 12; Fig. 1, par. 0184) arranged to receive a gas including nitrogen and oxygen (reactant gas can be atmospheric air/ambient air, par. 0015, 0183; atmospheric air has approximately 21% oxygen and 78% nitrogen by volume, par. 0381); an outlet (sample gas out near gas analysis sensor pack 54; Fig. 1); a pair of electrodes arranged downstream of the inlet (electrodes 24 downstream of reactant gas intake 12; Fig. 1) and configured to generate nitric oxide from the gas (electrodes 24 produce NO from the reactant gas; par. 0184); a nitric oxide sensor (gas analysis sensor pack 54, Fig. 1) arranged to measure a concentration of nitric oxide downstream of the pair of electrodes (gas sensor chamber measures NO levels in the product gas, par. 0186); and a controller (treatment controller 30; Fig. 1) in communication with the pair of electrodes and the nitric oxide sensor (Fig. 1 shows electrodes 24 and nitric oxide sensor 54 are in communication with the controller 30), wherein the controller is configured to selectively adjust a signal sent to the pair of electrodes (controller communicates with electrodes to control the concentration of NO in the product gas; par. 0184) to provide an inhaled concentration of nitric oxide between 50 ppm and 5000 ppm at the outlet (NO is present in concentration between 50-5000 ppm depending on the desired dose and inspiratory flow; par. 0484) for treating or preventing a respiratory disease (treatment of respiratory ailments; par. 0003).
Zapol does not explicitly disclose for treating or preventing viral respiratory infection.
Hein teaches that inhaled nitric oxide may be used in treating viral respiratory infection (Hein outlines multiple trials ongoing regarding the use of nitric oxide in treating COVID-19).
Therefore, it would have been obvious to one having ordinary skill in the art before the effective filing date of the invention to modify Zapol to be used for treating viral respiratory infection as taught by Hein.
Zapol does not explicitly disclose an inhaled concentration of nitric oxide greater than or equal to about 150 ppm.
However, it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to modify the concentration of Zapol from between 50 ppm and 5000 ppm to greater than or equal to about 150 ppm, as claimed, since the ranges overlap between 150 ppm and 5000 ppm and it has been held that “[i]n the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art' a prima facie case of obviousness exists”. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). Further, it would have been obvious to find the optimal inhaled concentration for optimal treatment since determining this optimal concentration only requires routine skill in the art and Zapol discloses that a desired dose can be generated (par. 0484).
Regarding claim 10, Zapol discloses the nitric oxide generator of claim 9 (shown above), further comprising an accumulator (reservoir 18; Fig. 1) in communication with a pressure regulator (altitude compensator 34; Fig. 1, par. 0384-0385).
Regarding claim 11, Zapol discloses the nitric oxide generator of claim 10 (shown above), wherein the accumulator is configured to add volume to a flow path between the inlet and the outlet (reservoir 18 holds a volume of gas in the flow path between inlet 12 and outlet, Fig. 1; air reservoir serves as an accumulator between the pump and plasma chamber, par. 0368) to store and maintain a pressure of the gas surrounding the pair of electrodes (flow and pressure within the plasma chamber can be varied by flow control means in communication with the air reservoir, par. 0476).
Regarding claim 12, Zapol discloses the nitric oxide generator of claim 9 (shown above), further comprising a pressure regulator (altitude compensator 34; Fig. 1, par. 0384-0385) configured to selectively adjust a pressure of the gas surrounding the pair of electrodes (variable flow restriction of the altitude compensator 34 is used to control pressure within the plasma chamber 22 wherein the electrodes 24 are located; par. 0385, Fig. 1).
Regarding claim 13, Zapol discloses the nitric oxide generator of claim 12 (shown above), wherein the controller is in communication with the pressure regulator (Fig. 1 shows altitude compensator 34 in communication with controller 30) and the controller is configured to selectively instruct the pressure regulator to adjust the pressure of the gas surrounding the pair of electrodes in response to the concentration of nitric oxide measured at the nitric oxide sensor (controller controls electrodes and pressure within chamber surrounding electrodes through altitude compensator to ensure accurate quantities of NO; par. 0385).
Regarding claim 14, Zapol discloses the nitric oxide generator of claim 13 (shown above), wherein the controller is configured to instruct the pressure regulator (altitude compensator 34) to increase the pressure of the gas surrounding the pair of electrodes to increase the concentration of nitric oxide at the outlet (altitude compensation increases pressure at the plasma chamber to increase NO output, par. 0385; gas sensor data is used to automatically adjust NO production to match a target level, par. 0411).
Regarding claim 15, Zapol discloses the nitric oxide generator of claim 13 (shown above), wherein the controller is configured to instruct the pressure regulator to decrease the pressure of the gas surrounding the pair of electrodes to decrease the concentration of nitric oxide at the outlet (gas sensor data is used to automatically adjust NO production to match a target level, par. 0411; lower pressure in the plasma chamber leads to less NO production, par. 0681; control algorithm input parameters include plasma chamber pressure which can be altered to adjust NO production rates, par. 0011, 0367, 0387).
Regarding claim 18, Zapol discloses the nitric oxide generator of claim 9 (shown above), further comprising a scavenger (filter-scavenger-filter 38; Fig. 1) arranged upstream of the outlet and downstream of the pair of electrodes (filter-scavenger-filter 38 is upstream of sample gas outlet at 54 and downstream of electrodes 24; Fig. 1).
Regarding claim 19, Zapol discloses the nitric oxide generator of claim 9 (shown above), further comprising a filter arranged upstream of the outlet and downstream of a scavenger (filter 50 is upstream of sample gas out at 54 and downstream of scavenger 38; Fig. 1).
Claim(s) 7-8 is/are rejected under 35 U.S.C. 103 as being unpatentable over Zapol in view of Crosbie (US 20150090261 A1).
Regarding claim 7, Zapol discloses the nitric oxide generator of claim 1 (shown above).
Zapol does not disclose further comprising a methemoglobin sensor adapted to sense a methemoglobin level in a patient.
Crosbie teaches a nitric oxide generator (abstract) comprising a methemoglobin sensor adapted to sense a methemoglobin level in a patient (controller receives information from a methemoglobin sensor, par. 0034-0035; methemoglobin levels of a patient can be measured to find a correlation between administered NO and methemoglobin level, par. 0086) for the purpose of monitoring effectiveness of NO treatment (high oxyhemoglobin and low methemoglobin indicates treatment success; par. 0087).
Therefore, it would have been obvious to one having ordinary skill in the art before the effective filing date of the invention to modify the nitric oxide generator of Zapol to comprise a methemoglobin sensor as taught by Crosbie for the purpose of monitoring effectiveness of NO treatment (Crosbie par. 0087).
Regarding claim 8, the modified Zapol discloses the nitric oxide generator of claim 7 (shown above).
The modified Zapol does not disclose wherein the controller is configured to monitor the methemoglobin level and instruct the pair of electrodes to decrease nitric oxide generation when the methemoglobin level reaches a predetermined threshold value.
Crosbie teaches a nitric oxide generator wherein the controller is configured to monitor the methemoglobin level (controller receives data from methemoglobin sensor; par. 0034) and instruct a pair of electrodes (pair of electrodes forms a spark gap 225; Fig. 3, par. 0054) to decrease nitric oxide generation when the methemoglobin level reaches a predetermined threshold value (NO level is reduced when methemoglobin level meets certain criteria, Crosbie par. 0087; amount of NO may be reduced in response to sensed parameters, par. 0032; NO production is adjusted by controlling spark intensity and/or duration, NO production is adjusted based on patient’s methemoglobin levels, par. 0018) for the purpose of adjusting production of NO responsive to a patient’s blood chemistry (par. 0018, 0035).
Therefore, it would have been obvious to one having ordinary skill in the art before the effective filing date of the invention to modify the nitric oxide generator of Zapol to decrease nitric oxide generation when methemoglobin level reaches a predetermined threshold value as taught by Crosbie for the purpose of adjusting production of NO responsive to a patient’s blood chemistry (par. 0018, 0035). This modification would also provide the benefit of avoiding methemoglobinemia which is a known toxicity of inhaled NO therapy (see par. 0005 of Flanagan et al. reference listed below).
Claim(s) 16-17 is/are rejected under 35 U.S.C. 103 as being unpatentable over Zapol, in view of Hein, and further in view of of Crosbie (US 20150090261 A1).
Regarding claim 16, the modified Zapol discloses the nitric oxide generator of claim 9 (shown above).
The modified Zapol does not disclose a methemoglobin sensor adapted to sense a methemoglobin level in a patient.
Crosbie teaches a nitric oxide generator (abstract) comprising a methemoglobin sensor adapted to sense a methemoglobin level in a patient (controller receives information from a methemoglobin sensor, par. 0034-0035; methemoglobin levels of a patient can be measured to find a correlation between administered NO and methemoglobin level, par. 0086) for the purpose of monitoring effectiveness of NO treatment (high oxyhemoglobin and low methemoglobin indicates treatment success; par. 0087).
Therefore, it would have been obvious to one having ordinary skill in the art before the effective filing date of the invention to modify the nitric oxide generator of Zapol to comprise a methemoglobin sensor as taught by Crosbie for the purpose of monitoring effectiveness of NO treatment (Crosbie par. 0087).
Regarding claim 17, the modified Zapol discloses the nitric oxide generator of claim 16 (shown above).
The modified Zapol does not disclose wherein the controller is configured to monitor the methemoglobin level and instruct the pair of electrodes to decrease nitric oxide generation when the methemoglobin level reaches a predetermined threshold value.
Crosbie teaches a nitric oxide generator wherein the controller is configured to monitor the methemoglobin level (controller receives data from methemoglobin sensor; par. 0034) and instruct a pair of electrodes (pair of electrodes forms a spark gap 225; Fig. 3, par. 0054) to decrease nitric oxide generation when the methemoglobin level reaches a predetermined threshold value (NO level is reduced when methemoglobin level meets certain criteria, Crosbie par. 0087; amount of NO may be reduced in response to sensed parameters, par. 0032; NO production is adjusted by controlling spark intensity and/or duration, NO production is adjusted based on patient’s methemoglobin levels, par. 0018) for the purpose of adjusting production of NO responsive to a patient’s blood chemistry (par. 0018, 0035).
Therefore, it would have been obvious to one having ordinary skill in the art before the effective filing date of the invention to modify the nitric oxide generator of Zapol to decrease nitric oxide generation when methemoglobin level reaches a predetermined threshold value as taught by Crosbie for the purpose of adjusting production of NO responsive to a patient’s blood chemistry (par. 0018, 0035). This modification would also provide the benefit of avoiding methemoglobinemia which is a known toxicity of inhaled NO therapy (see par. 0005 of Flanagan et al. reference listed below).
Response to Arguments
Applicant’s arguments with respect to claim(s) 1 have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Applicant's arguments filed 06/16/2026 regarding claim 9 have been fully considered but they are not persuasive.
Regarding claim 9, Applicant argues that Zapol does not disclose the specific claimed concentration of NO for treating or preventing a viral respiratory infection. However, Zapol discloses that a concentration of NO can be produced based on a desired dose and inspiratory flow (par. 0484). Zapol’s NO generator is capable of producing NO overlapping the specific claimed NO concentration of greater than or equal to 150ppm. Finding the optimal concentration for treatment would have only required routine skill in the art.
Applicant argues that Zapol does not disclose the claimed control architecture for providing a defined output concentration of NO. However, Zapol discloses multiple control parameters for adjusting the NO concentration, such as controlling electrode signaling (air flow, spark rate, spark duty cycle, can be varied to produced required NO concentrations, par. 0679; NO concentration can be produced based on a desired dose and inspiratory flow, par. 0484; controller includes sensors to sense the nitric oxide concentration in the patient inspiratory circuit such that the nitric oxide production can be adjusted based on feedback from the sensors, par. 0016). Therefore, Zapol discloses the claimed control architecture of controlling electrode signaling to provide a desired concentration of NO based on NO sensor data.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/K.R./Examiner, Art Unit 3785
/BRANDY S LEE/Supervisory Patent Examiner, Art Unit 3785
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