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
This action is responsive to the amendments filed 08/03/2026.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 38 is 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.
Claim 38 calls to a “maximum sensitivity” however it is unclear if the maximum sensitivity is an absolute value or an arbitrary value that is relative to the less than maximum sensitivity. If the value is an absolute value it is unclear what the value is. Thus, for the purpose of examination, the maximum sensitivity is being interpreted as relative such that the claimed “maximum sensitivity” and “less than maximum sensitivity” is achieved when the breath level trigger has a higher sensitivity than the breath slope trigger.
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.
Claims 7, 14-17, 21-23, 34-37 and 40 are rejected under 35 U.S.C. 103 as being unpatentable over Av-Gay (US 2016/0279165 A1) in view of Pelletier (US 2008/0078392 A1), Zheng (US 2014/0283833 A1), Acker (US 2014/0000596 A1), Form 8-K Bellerophon Therapeutics, as cited by applicant in IDS dated 07/02/2021, AckerJ (EP 2968828 B1) and Potenziano (US 2017/0232166 A1).
Regarding claim 7, Av-Gay discloses a method for improving or maintaining activity levels in a patient in need thereof (abstract, monitoring of parameters/vital signs is seen as activity levels, par 0306 discloses the method leading to improved or maintained activity levels), the method comprising: administering inhaled nitric oxide to the patient (par 0024) by:
(a) detecting a breath pattern in the patient including a total inspiratory time (par 0186-0187 discloses detecting breathing cycle phases including inhalation onset and exhalation onset, and determining duration of inhalation thus disclosing detecting a total inspiratory time);
(b) correlating the breath pattern with an algorithm to determine a timing of administration of a dose of nitric oxide (par 0186-0187 discloses coordinating a pulse delivery when a rate of intake increases, and coordinating the delivery to occur after a delay period on 20% of inhalation time); and
(c) administering the dose of nitric oxide to the patient in a pulsatile manner over a portion of the total inspiratory time (par 0186-0187),
wherein the algorithm uses a breath level threshold (par 0403 discloses a patient trigger wherein the trigger “detects a negative pressure Ptrigger from the patient indicating that the patient 18 is initiating inhalation”),
wherein the breath level threshold detects the breath when a negative pressure threshold is exceeded (par 0403 discloses detecting a breath/inhalation upon detection of a negative pressure threshold of Ptrigger),
wherein the dose of nitric oxide is adjusted based on the breath pattern (par 0187 discloses the period of time that NO is delivered is 60% of the inhalation period, as the inhalation period varies it is seen that the delivered dose thus changes dependent on the patients breathing pattern).
It is unclear from the disclosure of Av-Gay if the algorithm uses a threshold sensitivity AND a slope algorithm, wherein the slope algorithm detects a breath when a rate of pressure drop reaches a predetermined threshold. Av-Gay par 0186 discloses recognizing a rate of intake increasing thus disclosing a slope algorithm and par 0187 discloses a threshold set to 20% of the inspiratory time. Av-Gay par 0403 also discloses detecting pressure reaching a threshold of Ptrigger which is seen as a breath level threshold however it is unclear if there is further a threshold of a slope/rate of pressure drop.
Pelletier teaches a breath detection system that utilizes a breath level trigger (par 0029 discloses a detection threshold of a predetermined pressure) and a slope trigger (par 0029 discloses monitoring pressure change rate) functioning together, wherein the slope trigger detects a breath when a rate of pressure drop reaches a predetermined threshold (par 0029 “the detection threshold is generally indicative of a beginning of inhalation”, “the comparator 28 is configured to monitor the pressure change rate signal and to trip at a threshold that is slightly higher than the common mode voltage or detect when the pressure change rate signal fulfills a predetermined requirement” thus disclosing detecting a breath when a rate of pressure drop/pressure change rate reaches a threshold), and wherein the breath level trigger detects the breath when a low pressure threshold is exceeded (par 0029 discloses a pressure threshold indicating inhalation, par 0002 discloses inhalation causing a low pressure in the cannula).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to utilize the breath detection system of Pelletier in the method of Av-Gay as the system of Pelletier can detect the start of inhalation within 20 milliseconds (Pelletier par 0029) allowing for Av-Gay to administer iNO close to immediately after the start of inspiration and thus avoid a large delay in administration and wasted iNO that is delivered too late after the start of inhalation. Further, multiple inputs as taught by Peletier are oftentimes used with inhalation triggers in order to increase the sensitivity of the input while ensuring an accurate trigger, this also prevents missed triggers.
Modified Av-Gay does not expressly disclose a breath sensitivity control sets the breath level trigger and the slope trigger at different relative sensitivity levels.
Zheng teaches the use of multiple trigger parameters (par 0031 “one or more trigger parameters”) and a breath sensitivity control sets the triggers at different sensitivity levels (par 0031 “The one or more trigger parameters may be adjustable to facilitate detection of trigger events with different levels of trigger sensitivity. For the same activity by the subject, e.g. a particular pattern or volume of inhalation flow, a first trigger event may be detected based on a smaller change in the one or more output signals, and/or a smaller change in one or more parameters determined from the output signals, compared to a second trigger even”).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to utilize different sensitivity levels for the different triggers as doing so allows the triggers to actuate based on different patient response/effort amount thus preventing missed triggers as a secondary trigger with a differing sensitivity can act as a back-up.
Modified Av-Gay does not expressly disclose the dose of nitric oxide being adjusted per pulse based on the breath pattern, an overall dosage amount, and an ideal body weight of the patient.
Acker teaches delivery of iNO in a pulsatile manner (par 0002 discloses NO, par 0018 discloses providing the therapeutic gas in a pulsatile manner), wherein the does delivered in a pulse is dependent/adjusted per-pulse based on the breath pattern and an overall dosage amount (par 0037 “the pulse size may vary from one pulse to the next so that the total amount of therapeutic gas administered over a given time interval is constant, even though a patient's breathing rate may change”, par 0046 “if the patient's breathing rate and the cylinder concentration are known, then the CPU 115 can calculate how much volume of therapeutic gas needs to be administered each breath or set of breaths to provide the desired dosage of nitric oxide”).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention have the pulse dose of modified Av-gay be dependent on the breathing rate and the overall dosage to be delivered as doing so allows for the iNO to be delivered in a pulsatile manner that distributes the overall dosage dependent on patient breathing ensuring that the pulse dosage accommodates a specific user’s needs.
Modified Av-Gay does not expressly disclose the dose of nitric oxide being adjusted based on an ideal body weight of the patient.
Form 8-K discloses inhaled nitric oxide is administered at an overall dosage that is dependent on the ideal body weight of the patient (pg 2 “INOpulse device doses ranging from 3 to 75 mcg/kg IBW/hr”, IBW= ideal body weight).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have the overall dosage amount of modified Av-Gay/Acker be dependent on a patients ideal body weight as taught by Form 8-K, thus having the pulse dose also be dependent on the ideal body weight of the patient, as doing so ensures that the dose delivered to the patient is specific for their body thus preventing over and under dosing.
Modified Av-Gay remains silent to the dose of nitric oxide is delivered in a first third of the total inspiratory time.
AckerJ teaches a therapeutic gas delivery device (see title) for administering iNO (par 0029) wherein the dose of nitric oxide is delivered in a first third of the total inspiratory time (par 0049 “one or more of therapeutic gas are provided in the first half of inspiration or first third of inspiration).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have the method of modified Av-Gay deliver the iNO during the first third of the inspiration as taught by AckerJ as doing so can allow the method to deliver iNO in a timing or duration critical to the treatment regime (AckerJ: par 0049).
Modified Av-Gay remains silent to wherein a plurality of doses of nitric oxide are administered over a treatment period, and wherein the treatment period is at least 12 hours per day for at least 5 days.
Potenziano teaches the delivery of low doses of nitric oxide for a treatment period of at least 12 hours per day for at least 5 days (par 0125 “at least 12 hours a day for at least 10 days”).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to utilize a treatment period as claimed on the method of modified Av-Gay as taught by Potenziano as doing so allows for the nitric oxide to provide proper treatment for various conditions.
Regarding claim 14, modified Av-Gay discloses the method of claim 7. Av-Gay is silent to the overall dosage amount is about 25 micrograms (mcg)/kg ideal body weight (IBW)/hr to about 50 mcg/kg IBW/hr.
Form 8-K discloses the overall dosage amount is about 25 micrograms (mcg)/kg ideal body weight (IBW)/hr to about 50 mcg/kg IBW/hr (pg 2 “INOpulse device doses ranging from 3 to 75 mcg/kg IBW/hr”).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to utilize dosage ranges taught by Form 8-K in the method of Av-Gay as this is a range with confirmed efficacy and safety results (Form 8-K pg 2).
Regarding claim 15, modified Av-Gay discloses the method of claim 14. Av-Gay is silent to the overall dosage amount is about 30 mcg/kg IBW/hr to about 45 mcg/kg IBW/hr.
Form 8-K discloses the overall dosage amount is about 30 mcg/kg IBW/hr to about 45 mcg/kg IBW/hr (pg 2 “INOpulse device doses ranging from 3 to 75 mcg/kg IBW/hr”).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to utilize dosage ranges taught by Form 8-K in the method of Av-Gay as this is a range with confirmed efficacy and safety results (Form 8-K pg 2).
Regarding claim 16, modified Av-Gay discloses the method of claim 14. Av-Gay is silent to the overall dosage amount is about 30 mcg/kg IBW/hr.
Form 8-K discloses the overall dosage amount is about 30 mcg/kg IBW/hr (pg 2 “INOpulse device doses ranging from 3 to 75 mcg/kg IBW/hr”).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to utilize dosage taught by Form 8-K in the method of Av-Gay as this is a dosage with confirmed efficacy and safety results (Form 8-K pg 2).
Regarding claim 17, modified Av-Gay discloses the method of claim 14. Av-Gay is silent to the overall dosage amount is about 45 mcg/kg IBW/hr.
Form 8-K discloses the overall dosage amount is about 45 mcg/kg IBW/hr (pg 2 “INOpulse device doses ranging from 3 to 75 mcg/kg IBW/hr”).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to utilize dosage taught by Form 8-K in the method of Av-Gay as this is a dosage with confirmed efficacy and safety results (Form 8-K pg 2).
Regarding claim 21, modified Av-Gay discloses the method of claim 7. Av-Gay further discloses wherein the patient has interstitial lung disease (par 0311 ln 16-17 discloses ILD as a disease treatable by the disclosed method) and wherein the interstitial lung disease comprises one or more subtypes selected from idiopathic interstitial pneumonia (IIP) (par 0311 ln 12-13), chronic hypersensitivity pneumonia (par 0311 ln 18-19), occupational or environmental lung disease, idiopathic pulmonary fibrosis (IPF) (par 0311 ln 12 and 26), non-IPF IIPs, granulomatous, and connective tissue disease related ILD (par 0311 ln 20-21).
Regarding claim 22, modified Av-Gay discloses the method of claim 7. Av-Gay further discloses wherein the patient has interstitial lung disease (par 0311 ln 16-17 discloses ILD as a disease treatable by the disclosed method) and wherein the interstitial lung disease comprises idiopathic pulmonary fibrosis (IPF) (par 0311 ln 12 and 26).
Regarding claim 23, modified Av-Gay discloses the method of claim 7. Av-Gay further discloses the patient is at high risk of developing pulmonary hypertension (par 0006 discloses the method being used to prevent pulmonary hypertension thus disclosing the patient being at high risk).
Regarding claim 34, modified Av-Gay discloses the method of claim 7. Potenziano further teaches the treatment period is at least 16 hours per day for at least 5 days (par 0126 disclosing 16 hours a day and par 0125 disclosing at least 5 days).
Regarding claim 35, modified Av-Gay discloses the method of claim 7. Potenziano further teaches the treatment period is at least 12 hours per day for at least 8 weeks (par 0125 disclosing 12 hours a day and 2 months).
Regarding claim 36, modified Av-Gay discloses the method of claim 7. Potenziano further teaches the treatment period is at least 12 hours per day for at least 16 weeks (par 0125 disclosing 12 hours a day and 4 months).
Regarding claim 37, modified Av-Gay discloses the method of claim 7. Modified Av-Gay further discloses the dose per-pulse is determined as (mcg/kg IBW/hr) x (IBW in kg) x (1/respiratory rate) to maintain the overall dosage amount (as modified Av-Gay discloses the overall dosage being in terms of mcg/kg IBW/hr administering a dosage to a person requires the dosage to be multiplied by the users IBW in kg and further, further as Acker discloses the dose per pulse being adjusted based on the user’s breathing rate to maintain an overall dosage it is seen that the resulting mcg/hr would need to be divided by a respiratory rate of breaths/hr to determine the resulting pulse amount of mcg/breath).
Regarding claim 40, modified Av-Gay discloses the method of claim 7. Modified Av-Gay does not expressly disclose the predetermined threshold is configured to detect short, shallow breaths. However, Peletier discloses the intention of resolving the issue of shallow breaths not being detected by a pressure threshold (par 0004) and discloses using a slope algorithm allows for detection based on fast pressure drop at the start of inhalation (par 0027). Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to ensure that the predetermined threshold of modified Av-Gay is equipped to detect short, shallow breaths that may not be detected by the negative pressure threshold itself.
Claim 19 is rejected under 35 U.S.C. 103 as being unpatentable over modified Av-Gay as applied to claim 7 above, and further in view of Freitag (WO 2008/019102 A2).
Regarding claim 19, modified Av-Gay discloses the method of claim 7. Av-Gay further discloses measuring changes in activity levels using noninvasive measures (par 0246-0247, 0274, 0303).
Av-Gay does not expressly disclose the noninvasive measures to be actigraphy.
Freitag teaches a method of providing respiratory support to a patient (abstract) involving measuring changes in activity levels using actigraphy (pg 32 ln 9-11).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to utilize actigraphy as taught by Freitag to measure activity levels in the method of Av-Gay as actigraphy is a well-known noninvasive way to evaluate a person’s activity levels.
Claim 38 is rejected under 35 U.S.C. 103 as being unpatentable over modified Av-Gay as applied to claim 7 above, and further in view of Flannagan (US 2014/0150789 A1).
Regarding claim 38, modified Av-Gay discloses the method of claim 7. Modified Av-Gay is silent to the breath level trigger is set at maximum sensitivity and the breath slope trigger is set at less than maximum sensitivity.
Flannagan teaches the use of a breath slope trigger in addition to a breath level trigger, as breath level triggers are known to result in delays (par 0167).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have the breath level trigger set to a maximum sensitivity in order to reduce delays and have the breath slope set to less than a maximum sensitivity as the slope trigger is able to avoid delays.
Claim 39 is rejected under 35 U.S.C. 103 as being unpatentable over modified Av-Gay as applied to claim 7 above, and further in view of Deane (US 7,841,343 B2).
Regarding claim 39, modified Av-Gay discloses the method of claim 7. Av-Gay does not expressly disclose the negative pressure threshold is -0.1 cm H2O to -1.0 cm H2O.
However, Deane discloses that the pressure threshold effects the triggering ability/efficacy of the gas delivered (col 6 ln 10-52, specifically ln 20-22 and ln 43-45). Thus, disclosing the negative pressure threshold is a result effective variable.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to ensure the negative pressure threshold of modified Av-Gay is within the claimed range in order to ensure proper triggering/gas delivery as a matter of routine optimization since it has been held that “where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Claims 41 is rejected under 35 U.S.C. 103 as being unpatentable over Av-Gay in view of Pelletier, Zheng, Acker, Form 8-K Bellerophon Therapeutics, as cited by applicant in IDS dated 07/02/2021, AckerJ, Potenziano, Freitag and Deane.
Regarding claim 41, Av-Gay discloses a method for improving or maintaining activity levels in a patient in need thereof (abstract, monitoring of parameters/vital signs is seen as activity levels, par 0306 discloses the method leading to improved or maintained activity levels), the method comprising: detecting a breath pattern in the patient including a total inspiratory time of each detected breath (par 0186-0187 discloses detecting breathing cycle phases including inhalation onset and exhalation onset, and determining duration of inhalation thus disclosing detecting a total inspiratory time); correlating the breath pattern with an algorithm to determine a timing of administration of a dose of nitric oxide (par 0186-0187 discloses coordinating a pulse delivery when a rate of intake increases, and coordinating the delivery to occur after a delay period on 20% of inhalation time) wherein the timing is determined to initiate delivery of the dose of nitric oxide within a predetermined maximum delay from an onset of inspiration, the predetermined maximum delay being less than 200 milliseconds (par 0188 discloses the pulse delay period ranging from 0-2500ms thus disclosing initiating delivery within a predetermined maximum delay can be 0-199ms); and administering the dose of nitric oxide to the patient in a pulsatile manner over a portion of the total inspiratory time (par 0186-0187),wherein the algorithm uses a breath level threshold (par 0403 discloses a patient trigger wherein the trigger “detects a negative pressure Ptrigger from the patient indicating that the patient 18 is initiating inhalation”),wherein the breath level threshold detects the breath when a negative pressure threshold is exceeded (par 0403 discloses detecting a breath/inhalation upon detection of a negative pressure threshold of Ptrigger),wherein the dose of nitric oxide is adjusted based on the breath pattern (par 0187 discloses the period of time that NO is delivered is 60% of the inhalation period, as the inhalation period varies it is seen that the delivered dose thus changes dependent on the patients breathing pattern).
It is unclear from the disclosure of Av-Gay if the algorithm uses a threshold sensitivity AND a slope algorithm, wherein the slope algorithm detects a breath when a rate of pressure drop reaches a predetermined threshold. Av-Gay par 0186 discloses recognizing a rate of intake increasing thus disclosing a slope algorithm and par 0187 discloses a threshold set to 20% of the inspiratory time. Av-Gay par 0403 also discloses detecting pressure reaching a threshold of Ptrigger which is seen as a breath level threshold however it is unclear if there is further a threshold of a slope/rate of pressure drop.
Pelletier teaches a breath detection system that utilizes a breath level threshold (par 0029 discloses a detection threshold of a predetermined pressure) and a slope algorithm (par 0029 discloses monitoring pressure change rate), wherein the slope algorithm detects a breath when a rate of pressure drop reaches a predetermined threshold (par 0029 “the detection threshold is generally indicative of a beginning of inhalation”, “the comparator 28 is configured to monitor the pressure change rate signal and to trip at a threshold that is slightly higher than the common mode voltage or detect when the pressure change rate signal fulfills a predetermined requirement” thus disclosing detecting a breath when a rate of pressure drop/pressure change rate reaches a threshold), and wherein the breath level threshold detects the breath when a low pressure threshold is exceeded (par 0029 discloses a pressure threshold indicating inhalation, par 0002 discloses inhalation causing a low pressure in the cannula).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to utilize the breath detection system of Pelletier in the method of Av-Gay as the system of Pelletier can detect the start of inhalation within 20 milliseconds (Pelletier par 0029) allowing for Av-Gay to administer iNO close to immediately after the start of inspiration and thus avoid a large delay in administration and wasted iNO that is delivered too late after the start of inhalation. Further, multiple inputs as taught by Peletier are often times used with inhalation triggers in order to increase the sensitivity of the input while ensuring an accurate trigger and preventing missed triggers therefore it would have further been obvious to one of ordinary skill in the art to utilize the triggers concurrently such that either/both trigger(s) can detect inspiration.
Modified Av-Gay does not expressly disclose a breath sensitivity control sets the breath level trigger and the slope trigger at different relative sensitivity levels.
Zheng teaches the use of multiple trigger parameters (par 0031 “one or more trigger parameters”) and a breath sensitivity control sets the triggers at different sensitivity levels (par 0031 “The one or more trigger parameters may be adjustable to facilitate detection of trigger events with different levels of trigger sensitivity. For the same activity by the subject, e.g. a particular pattern or volume of inhalation flow, a first trigger event may be detected based on a smaller change in the one or more output signals, and/or a smaller change in one or more parameters determined from the output signals, compared to a second trigger even”).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to utilize different sensitivity levels for the different triggers as doing so allows the triggers to actuate based on different patient response/effort amount thus preventing missed triggers as a secondary trigger with a differing sensitivity can act as a back-up.
Modified Av-Gay does not expressly disclose the predetermined threshold is configured to detect short, shallow breaths. However, Peletier discloses the intention of resolving the issue of shallow breaths not being detected by a pressure threshold (par 0004) and discloses using a slope algorithm allows for detection based on fast pressure drop at the start of inhalation (par 0027). Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to ensure that the predetermined threshold of modified Av-Gay is equipped to detect short, shallow breaths that may not be detected by the negative pressure threshold itself.
Modified Av-Gay does not expressly disclose the dose of nitric oxide being adjusted per pulse based on the breath pattern, an overall dosage amount, and an ideal body weight of the patient wherein the dose per-pulse is determined as (mcg/kg IBW/hr) x (IBW in kg) x (1/respiratory rate) to maintain the overall dosage amount.
Acker teaches delivery of iNO in a pulsatile manner (par 0002 discloses NO, par 0018 discloses providing the therapeutic gas in a pulsatile manner), wherein the does delivered in a pulse is dependent/adjusted per-pulse based on the breath pattern and an overall dosage amount (par 0037 “the pulse size may vary from one pulse to the next so that the total amount of therapeutic gas administered over a given time interval is constant, even though a patient's breathing rate may change”, par 0046 “if the patient's breathing rate and the cylinder concentration are known, then the CPU 115 can calculate how much volume of therapeutic gas needs to be administered each breath or set of breaths to provide the desired dosage of nitric oxide”).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention have the pulse dose of modified Av-gay be dependent on the breathing rate and the overall dosage to be delivered as doing so allows for the iNO to be delivered in a pulsatile manner that distributes the overall dosage dependent on patient breathing ensuring that the pulse dosage accommodates a specific user’s needs.
Modified Av-Gay does not expressly disclose the dose of nitric oxide being adjusted based on an ideal body weight of the patient.
Form 8-K discloses inhaled nitric oxide is administered at an overall dosage that is dependent on the ideal body weight of the patient (pg 2 “INOpulse device doses ranging from 3 to 75 mcg/kg IBW/hr”, IBW= ideal body weight).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have the overall dosage amount of modified Av-Gay/Acker be dependent on a patients ideal body weight as taught by Form 8-K, thus having the pulse dose also be dependent on the ideal body weight of the patient, as doing so ensures that the dose delivered to the patient is specific for their body thus preventing over and under dosing.
Therefore modified Av-Gay discloses wherein the dose per-pulse is determined as (mcg/kg IBW/hr) x (IBW in kg) x (1/respiratory rate) to maintain the overall dosage amount (as modified Av-Gay discloses the overall dosage being in terms of mcg/kg IBW/hr administering a dosage to a person requires the dosage to be multiplied by the users IBW in kg and further, further as Acker discloses the dose per pulse being adjusted based on the user’s breathing rate to maintain an overall dosage it is seen that the resulting mcg/hr would need to be divided by a respiratory rate of breaths/hr to determine the resulting pulse amount of mcg/breath).
Modified Av-Gay remains silent to at least 90% of the dose is delivered during a first third of the total inspiratory time.
AckerJ teaches a therapeutic gas delivery device (see title) for administering iNO (par 0029) wherein the dose of nitric oxide is delivered in a first third of the total inspiratory time (par 0049 “one or more of therapeutic gas are provided in the first half of inspiration or first third of inspiration).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have the method of modified Av-Gay deliver the iNO during the first third of the inspiration as taught by AckerJ as doing so can allow the method to deliver iNO in a timing or duration critical to the treatment regime (AckerJ: par 0049).
Modified Av-Gay remains silent to wherein a plurality of doses of nitric oxide are administered over a treatment period, and wherein the treatment period is at least 12 hours per day for at least 5 days.
Potenziano teaches the delivery of low doses of nitric oxide for a treatment period of at least 12 hours per day for at least 5 days (par 0125 “at least 12 hours a day for at least 10 days”).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to utilize a treatment period as claimed on the method of modified Av-Gay as taught by Potenziano as doing so allows for the nitric oxide to provide proper treatment for various conditions.
While Av-Gay further discloses monitoring activity levels of the patient using noninvasive measures (par 0246-0247, 0274, 0303), Av-Gay does not expressly disclose the noninvasive measures to be an actigraphy monitor.
Freitag teaches a method of providing respiratory support to a patient (abstract) involving measuring changes in activity levels using actigraphy (pg 32 ln 9-11).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to utilize actigraphy as taught by Freitag to measure activity levels in the method of modified Av-Gay as actigraphy is a well-known noninvasive way to evaluate a person’s activity levels.
Lastly, Av-Gay remains silent to the negative pressure threshold is -0.1 cm H2O to -1.0 cm H2O.
However, Deane discloses that the pressure threshold affects the triggering ability/efficacy of the gas delivered (col 6 ln 10-52, specifically ln 20-22 and ln 43-45). Thus, disclosing the negative pressure threshold is a result effective variable.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to ensure the negative pressure threshold of modified Av-Gay is within the claimed range in order to ensure proper triggering/gas delivery as a matter of routine optimization since it has been held that “where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Response to Arguments
Applicant’s arguments with respect to claims 7 and 41 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.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
US 2013/0087146 A1 discloses a pressure slope trigger
US 2018/0243528 A1 discloses iNO delivery in a pulsatile manner that utilizes the prescribed dose and patients respiratory parameters to determine pulse duration, flow rate and concentration
US 6,109,260 disclose detecting negative pressure as an inhalation trigger
US 2003/0172929 A1 discloses tidal volume-dependent regulation of gas dosing
US 5,427,797 discloses administering NO to a patient and comparing heart rate and oxygen saturation of a baseline and after a NO inhalation period
US 2006/0147553 A1 discloses administering inhaled nitric oxide upon inspiratory demand
US 6,581,599 B1 discloses a device for delivering NO to a patient comprising a flow profile sensor
US 2012/0107423 A1 discloses a method for using inhaled nitric oxide to treat respiratory distress syndrome
US 8,408,206 B2 discloses a system that delivers a pulse of therapeutic gas to a patient based upon a patient trigger sensor
US 2014/0275901 A1 discloses monitoring oxygenation parameters during treatment/delivery of NO
US 2018/0304038 A1 discloses delivering nitric oxide to a patient that enables higher activity of the patient
US 2018/0071467 A1 discloses a method for portable NO delivery
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KIRA B DAHER whose telephone number is (571)270-0190. The examiner can normally be reached M-F 8am-5pm.
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/K.B.D./Examiner, Art Unit 3785
/BRADLEY H PHILIPS/Primary Examiner, Art Unit 3799
