DETAILED ACTION
Drawings
The drawings are objected to because FIGS. 1E, 3A and 3B (described in the specification) are not included in the drawings.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Abstract
The abstract of the disclosure is objected to because it is unclear due to syntax, editorial and/or antecedent error(s). Going forward with examination, the abstract is interpreted to be (Note that in applicant’s response, where a change is requested in the abstract, a separate page of the abstract containing the change will be needed):
--The present disclosure provides novel approaches novel approaches to s of compromised lung function and methods for measuring or assessing s assess efficacy treatments of compromised lung function where the compromised lung function is caused by primary ciliary dyskinesia and where the methods include measuring fractional nitric oxide concentration and hydrogen peroxide concentration in a patient before [[the]] an initiation of a treatment and at various timepoints following the initiation of the treatment.--
Correction is required. See MPEP § 608.01(b).
Specification
The disclosure (specification) is objected to because it is unclear due to syntax, editorial and/or antecedent errors. Going forward with examination, the following specification paragraphs are interpreted to be (Note that in applicant’s response, where a change is requested in the specification, an entire paragraph of the specification containing the change will be needed):
--[0002] The general field of the present disclosure are novel approaches to s of compromised lung function and methods for measuring or assessing
--[0003] Primary ciliary dyskinesia (PCD) is a rare genetic ciliopathy in which mucociliary clearance is disturbed by the abnormal motion of cilia or there is a severe reduction in the generation of multiple motile cilia. Compromised lung function or lung damage ensues due to recurrent airway infections, sometimes even resulting in respiratory failure. So far, no causative treatment is available and treatment efforts are primarily aimed at improving mucociliary clearance and early treatment of bacterial airway infections. Treatment guidelines are largely based on cystic fibrosis (CF) guidelines, as few studies have been performed on PCD.--
--[0006] However, what is needed is an understanding of whether antigen stasis in PCD could damage the PCD epithelium through nitrosative and oxidative stress. This oxidative stress, in turn, could decrease gas phase NO concentrations, increase lung concentrations of oxidants such as hydrogen peroxide and contribute to airway nitrosative stress. Further, what is needed are ways to monitor the effectiveness of treatments that set out to alleviate this airway oxidative stress in patients with compromised lung function. The present invention addresses these needs.--
--[0007] The present disclosure provides novel approaches to s of compromised lung function and methods for measuring or assessing the effectiveness of such treatments.
[0012] More specifically, current invention provides methods of assessing concentration in the exhaled breath of the patient before [[the]] an initiation of treatment and at various timepoints following the initiation of the treatment. In some embodiments, therapy or therapies comprise antioxidant therapy or
--[0013] In any embodiment, an increase in fractional nitric oxide concentration and a decrease in hydrogen peroxide concentration in the exhaled breath of the patient over time indicate positive efficacy of the antioxidant therapy.--
--[0019] In an embodiment of the invention is provided a method of assessing the efficacy of the treatment of compromised lung function in a patient, wherein the compromised lung function is caused by primary ciliary dyskinesia and wherein the treatment comprises administration of a therapy that modulates airway pH. This embodiment of the invention further comprises measuring fractional nitric oxide concentration and hydrogen peroxide concentration in the exhaled breath of the patient before the initiation of treatment and at various timepoints following the initiation of treatment.--
--[0020] In any embodiment, an increase in fractional nitric oxide concentration and a decrease in hydrogen peroxide concentration in the exhaled breath of the patient over time indicate positive efficacy of the of the treatment with an agent that modulates airway pH. In some embodiments, the agent that modulates airway pH increases airway pH. In still other embodiments, the agent is nebulized NaHCO.sub.3. In yet other embodiments, the therapy that modulates airway pH is the administration of noninvasive ventilation.--
--[0031] Primary ciliary dyskinesia (PCD) is a rare genetic ciliopathy in which mucociliary clearance is disturbed by the abnormal motion of cilia or there is a severe reduction in the generation of multiple motile cilia. Compromised lung function or lung damage ensues due to recurrent airway infections, sometimes even resulting in respiratory failure. So far, no curative treatment is available and treatment efforts are primarily aimed at improving mucociliary clearance and early treatment of bacterial airway infections. Treatment guidelines are largely based on cystic fibrosis (CF) guidelines, as few studies have been performed on PCD. However, what is needed is an understanding as to how or why PCD airway cells might not efficiently clear antigens from the epithelial surface, resulting in increased oxidative stress. This oxidative stress, in turn, could both decrease gas phase NO concentrations and contribute to airway nitrosative stress. Further, what is needed are ways to monitor the effectiveness of treatments that set out to alleviate this airway oxidative stress in patients with compromised lung function.--
--[0033] More specifically, current invention provides methods of assessing the efficacy of therapies used in the treatment of a patient with compromised lung function comprising measuring fractional nitric oxide concentration and hydrogen peroxide concentration in the exhaled breath of the patient before the initiation of treatment and at various timepoints following the initiation of treatment. In some embodiments, therapy or therapies comprise antioxidant therapy or the administration of one or more antioxidants.--
--[0034] In any embodiment, an increase in fractional nitric oxide concentration and a decrease in hydrogen peroxide concentration in the exhaled breath of the patient over time indicate positive efficacy of the antioxidant therapy.--
--[0040] In an embodiment of the invention is provided a method of assessing the efficacy of the treatment of compromised lung function in a patient, wherein the compromised lung function is caused by primary ciliary dyskinesia and wherein the treatment comprises administration of [[an]] a therapy that modulates airway pH. This embodiment of the invention further comprises measuring fractional nitric oxide concentration and hydrogen peroxide concentration in the exhaled breath of the patient before the initiation of treatment and at various timepoints following the initiation of treatment.--
--[0041] In any embodiment, an increase in fractional nitric oxide concentration and a decrease in hydrogen peroxide concentration in the exhaled breath of the patient over time indicate positive efficacy of the of the treatment with an agent that modulates airway pH. In some embodiments, the agent that modulates airway pH increases airway pH. In still other embodiments, the agent is nebulized NaHCO3. In yet other embodiments, the therapy that modulates airway pH is the administration of noninvasive ventilation.--
--[0097] FIG. 1A-E shows the clearance of fluorescently labeled Derp1 from the apical surface of ciliated HC and PCD human airway epithelial cells (HAECs). FIG. 1A: in this model, HAECs (HC and PCD) were grown on Transwell filters until fully ciliated (4-6) weeks. A fenestration was then cut circumferentially in the filter in a 90º arc, such that the apical (ciliated) surface was in contact with the basolateral medium. Fluorescently labeled Derp1 (Alexa-Fluor 647) was applied to the cell surface, and fluorescent images were obtained from the center of the field obtained at times 0, 1, and 2 hr. Counts of labeled Derp1 were made by three blinded observers. FIG. 1B: negative control (no Derp-1 added) shows essentially no background autofluorescence. FIG. 1C, 1D: representative images of labeled Derp-1 on the surface of HAECs: FIG. 1D = HC's; FIG. 1E = PCD cells (CCNO genotype); FIG. 1E: quantitation of Derp1-f in cells from HC; (green; n = 3 filters each from five subjects) and patients with PCD (CCNO; orange, n = 9 filters and DNAH11; purple, n = 6 filters). In HC cells, label decreased, comparing time 0 to 2 hr (p = 0.001). In PCD cells, there was no difference in signal between time 0, time 1 and 2 hr, either for PCD as a whole or for either CCNO or DNAH11 (p = NS). Bars in FIGS. 1B, 1C and 1D =150 um.--
--[0123] There are other potential reasons for decreased nNO in PCD, but none are compelling. Denitrifying organisms colonizing the airway lead to a modest (low ppb) decrease airway NO in CF and could contribute to decreased nNO in PCD, with the caveats that i) these organisms are generally less common colonizers in PCD than in CF, and ii) airway NO levels are overall somewhat higher in CF than in PCD. See Gaston et al., “Nitrogen redox balance in the cystic fibrosis airway: effects of antipseudomonal therapy,” (2002) Am J Respir Crit Care Med 165: pp. 387-390; Wijers et al., “Bacterial infections in patients with primary ciliary dyskinesia: Comparison with cystic fibrosis,” (2017) Chron Respir Dis 14: pp. 392-406. Airway pH can affect airway NO levels, but PCD patients (unlike CF patients) have no intrinsic reason to have low airway epithelial surface pH. Arginine, citrulline and ADMA metabolism are not known to be disordered in PCD patients; nor is S-nitrosothiol metabolism: these factors are unlikely to cause uniformly low nNO production rate values in PCD relative to HC or to other conditions. See Marozkina et al., “Nitrogen chemistry and lung physiology,” (2015) Annu Rev Physiol 77: pp. 431-452.
The current disclosure underscores the importance of airway clearance, exercise and cough in moving antigens out of the PCD airway. Antigen stasis and oxidative/nitrosative stress appear likely to injure the airway epithelium. The invention provides a method to determine the efficacy of airway clearance over time by fractional nitric oxide concentration and hydrogen peroxide concentration in the exhaled breath of the patient before the initiation of treatment and at various timepoints following the initiation of treatment. Thus, an increase in fractional nitric oxide concentration and a decrease in hydrogen peroxide concentration in the exhaled breath of the patient over time indicate positive efficacy of treatments such as antioxidant therapy which can be used in patients with PCD and other patients with compromised lung function.--
--[0127] Methods of assessing the efficacy of therapies used in the treatment of a patient with compromised lung function comprising measuring fractional nitric oxide concentration and hydrogen peroxide concentration in the exhaled breath of the patient before the initiation of treatment and at various timepoints following the initiation of treatment.--
--[0128] Methods of assessing the efficacy of therapies used in the treatment of a patient with compromised lung function comprising measuring fractional nitric oxide concentration and hydrogen peroxide concentration in the exhaled breath of the patient before the initiation of treatment and at various timepoints following the initiation of treatment where the therapy or therapies comprise antioxidant therapy or the administration of one or more antioxidants.--
--[0129] Methods of assessing the efficacy of therapies used in the treatment of a patient with compromised lung function where an increase in fractional nitric oxide concentration and a decrease in hydrogen peroxide concentration in the exhaled breath of the patient over time indicate positive efficacy of the antioxidant therapy.--
--[0138] Methods of assessing the efficacy of the treatment of compromised lung function in a patient, thereof wherein the compromised lung function is caused by primary ciliary dyskinesia and wherein the treatment comprises administration of an agent that modulates airway pH where the method comprises measuring fractional nitric oxide concentration and hydrogen peroxide concentration in the exhaled breath of the patient before the initiation of treatment and at various timepoints following the initiation of treatment.--
--[0139] Methods of assessing the efficacy of therapies used in the treatment of a patient with compromised lung function thereof wherein the compromised lung function is caused by primary ciliary dyskinesia where an increase in fractional nitric oxide concentration and a decrease in hydrogen peroxide concentration in the exhaled breath of the patient over time indicate positive efficacy of treatment that modulates airway pH.--
Appropriate correction is required.
Claim Objections
Claims 1-4, 6-10 and 12-19 are objected to because they are unclear due to syntax, editorial and/or antecedent errors. In order to overcome the objections, please see the 101 rejections below.
Appropriate correction is required.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-20 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., an abstract idea) without significantly more.
Independent claim 1 essentially recites a method of assessing efficacy of an antioxidant therapy for treating primary ciliary dyskinesia in a patient, the method comprising measuring fractional nitric oxide concentration and hydrogen peroxide concentration in exhaled breath of the patient before initiation of the therapy and at various timepoints following the initiation of therapy. The method, as claimed, is a judicial exception because it appear merely a mental process practiced mentally and not integrated into any of the physical statutory patentable categories: process, machine, manufacture, or composition of matter. For instant, the claim recites “an antioxidant therapy” but without reciting what the antioxidant therapy entails and how to perform it physically. The claim also recites “measuring…” but fails to recite how to measure (similarly, “a carpet configured to fly”). One would not be able to physically practice claim 1.
Independent claim 6 essentially recites a method of treating primary ciliary dyskinesia in a patient, comprising a therapy that modulates airway pH in the patient’s airway. The method, as claimed, is a judicial exception. For instant, the claim essentially recites “a therapy that modulates airway pH in the patent’s airway” but fails to recite what the therapy entails and how to perform it physically. One would not be able to physically practice claim 6.
Independent claim 12 essentially recites a method of assessing efficacy of treatment of primary ciliary dyskinesia in a patient, wherein the treatment comprises administration of a therapy that modulates airway pH in the patient’s airway, the method comprising measuring fractional nitric oxide concentration and hydrogen peroxide concentration in exhaled breath of the patient before initiation of the therapy and at various timepoints following the initiation of the therapy. The method, as claimed, is a judicial exception. For instant, the claim essentially recites “a therapy that modulates airway pH in the patent’s airway” but fails to recite what the therapy entails and how to perform it physically. The claim also recites “measuring…” but fails to recite how to measure. One would not be able to physically practice claim 12.
Claims 1, 6 and 12 further fail to include any additional elements that are sufficient to amount to significantly more than the judicial exception, and have a practical application (See MPEP 2106).
The remaining claims are dependent on claims 1, 6 and 12. Thus they all fall together.
Going forward with examination, the claims are interpreted to be (based on applicant’s disclosure as a whole):
--1. A method of assessing an antioxidant therapy in a patient with primary ciliary dyskinesia, the antioxidant therapy comprising administering one or more antioxidant agents to the patient via oral, inhalation, intravenous, subcutaneous, sublingual, or transdermal;
the method comprising:
using a point-of-care device to collect respective samples of exhaled breath from the patient respectively before initiation of the therapy and during the therapy;
using an analyzer to measure concentration in the respective samples of the exhaled breath the therapy and at various timepoints following the initiation of the therapy; and
indicating a positive efficacy of the therapy when the analyzer measures an increase in the fractional nitric oxide concentration and a decrease in the hydrogen peroxide concentration in the samples of the exhaled breath over time.--
--3. The method of claim 1, wherein the antioxidant agents is selected from [[the]] a group consisting of N-acetylcysteine, Nacystelyn, N-isobutyrlcysteine, carbocisteine, procysteine, erdosteine, thioredoxin, 15d-PGJ2, CDDO-imidazolide, sulforaphane, chalcones, superoxide dismutase, ebselen, molecular hydrogen, celastrol, 2-thioxanthine, glutathione, vitamin A (retinol) β-carotenes, vitamin C (ascorbic acid), vitamin D (cholecalciferol), vitamin E (gamma and/or alpha tocopherol), lipo-glutathione (glutathione) and coenzyme Q (ubiquinone).--
--6. A method of treating primary ciliary dyskinesia in a patient in need thereof comprising a therapy that modulates airway pH in the patient’s airway by using a nebulizer to administer nebulized NaHCO3 to the patient, or a noninvasive positive-pressure ventilator without an endotracheal airway to augment alveolar ventilation of the patient.--
--7. The method of claim 6, wherein the therapy the airway pH in the patient’s airway.--
--10. The method of claim 3, wherein the therapy further comprises modulating airway pH in the patient’s airway by using a nebulizer to administer nebulized NaHCO3 to the patient, or a noninvasive positive-pressure ventilator without an endotracheal airway to augment alveolar ventilation of the patient.--
11. The method of claim 6, wherein the primary ciliary dyskinesia is exacerbated by one or more of one or more of asthma, exposure to cigarette smoke, exposure to atmospheric pollutants, chronic obstructive pulmonary disease, bronchitis, cystic fibrosis, extended post-viral bronchial hyperresponsiveness syndrome, rhinosinusitis, reactive airways dysfunction syndrome, and persistent allergen exposure.
--12. A method of assessing a therapy in a patient with primary ciliary dyskinesia, the therapy comprising modulating airway pH in the patient’s airway by using a nebulizer to administer nebulized NaHCO3 to the patient, or a noninvasive positive-pressure ventilator without an endotracheal airway to augment alveolar ventilation of the patient,
the method comprising:
using a point-of-care device to collect respective samples of exhaled breath from the patient respectively before initiation of the therapy and during the therapy;
using an analyzer to measure concentration in the respective samples of the exhaled breath the therapy and at various timepoints following the initiation of the therapy; and
indicating a positive efficacy of the therapy when the analyzer measures an increase in the fractional nitric oxide concentration and a decrease in the hydrogen peroxide concentration in the respective samples of the exhaled breath over time.--
--14. The method of claim 12, wherein the therapy the airway pH in the patient’s airway.--
--17. The method of claim 12, wherein the therapy further comprises administering one or more agents to the patient via oral, inhalation, intravenous, subcutaneous, sublingual, or transdermal.--
--18. The method of claim 17, wherein the one or more antioxidant agents is selected from [[the]] a group consisting of N-acetylcysteine, Nacystelyn, N-isobutyrlcysteine, carbocisteine, procysteine, erdosteine, thioredoxin, 15d-PGJ2, CDDO-imidazolide, sulforaphane, chalcones, superoxide dismutase, ebselen, molecular hydrogen, celastrol, 2-thioxanthine, glutathione, vitamin A (retinol) β-carotenes, vitamin C (ascorbic acid), vitamin D (cholecalciferol), vitamin E (gamma tocopherol), lipo-glutathione (glutathione) and coenzyme Q (ubiquinone).--
20. The method of claim 12, wherein the primary ciliary dyskinesia is exacerbated by one or more of asthma, exposure to cigarette smoke, exposure to atmospheric pollutants, chronic obstructive pulmonary disease, bronchitis, cystic fibrosis, extended post-viral bronchial hyperresponsiveness syndrome, rhinosinusitis, reactive airways dysfunction syndrome, and persistent allergen exposure.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 6, 7 and 11 (as interpreted above) are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Burch (US 2019/0231686 A1).
Burch teaches:
6. A method of treating primary ciliary dyskinesia (Pars. 0049, 0051, 0053, 0088, 0125: “primary ciliary dyskinesia [PCD]”) in a patient in need thereof comprising a therapy that modulates airway pH in the patient’s airway (Pars. 0002, 0048, 0051, 0057) by using a nebulizer to administer nebulized NaHCO3 to the patient, or a noninvasive positive-pressure ventilator without an endotracheal airway to augment alveolar ventilation of the patient (Par. 0084: “Mists or aerosols of particles comprising the active compounds can be produced by any suitable means, such as by nebulization… Administration can be by pressure-driven aerosol nebulizer…”).
Par. 0002: “The treatment restores hydration, increases pH and antimicrobial defense while reducing inflammation…”
Par. 0048: “Therefore, this invention is a combination formulation comprised of ingredient components that…help balance mucosal surface pH…”
Par. 0051: “The present invention provides a method of treating and/or managing inflammatory and/or infectious diseases affecting mucosal surfaces by administering a combination drug therapy… In particular, treating cystic fibrosis includes causing one or more of the following: increasing FEV1, increasing blood oxygen saturation, enhanced CFTR activity, augmented airway hydration, raising airway surface liquid pH…”
Par. 0057: “A third aspect of the invention is the upward adjustment of mucosal surface pH. Failure of defective CFTR to transport bicarbonate results in an airway surface liquid pH that is lower in CF than in normal individuals.”
7. The method of claim 6, wherein the therapy increases the airway pH in the patient’s airway (as discussed above in claim 6; Pars. 0002, 0051, 0057).
11. The method of claim 6, wherein the primary ciliary dyskinesia is exacerbated by one or more of one or more of asthma, exposure to cigarette smoke (as is in a case of a smoker; Par. 0053), exposure to atmospheric pollutants, chronic obstructive pulmonary disease, bronchitis, cystic fibrosis, extended post-viral bronchial hyperresponsiveness syndrome, rhinosinusitis, reactive airways dysfunction syndrome, and persistent allergen exposure.
(Note that this claim appears to recite an inherent feature of primary ciliary dyskinesia and/or a natural phenomenon related to primary ciliary dyskinesia , thus may not be patentable).
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 1, 3, 10, 12, 14, 17-18 and 20 (as interpreted above) are rejected under 35 U.S.C. 103 as being unpatentable over Burch.
1. Burch teaches a method of assessing efficacy of an antioxidant therapy in a patient with primary ciliary dyskinesia (Pars. 0049, 0051, 0053, 0088, 0125: “primary ciliary dyskinesia [PCD]”), the antioxidant therapy comprising administering one or more antioxidant agents (for general protection against oxidative stress and to reduce production of pro-inflammatory cytokines and/or other markers of inflammation; Pars. 0041, 0059) to the patient via oral, inhalation, intravenous, subcutaneous, sublingual, or transdermal (Par. 0084: “Mists or aerosols of particles comprising the active compounds can be produced by any suitable means, such as by nebulization, or by a simple nasal spray with the active agent in an aqueous pharmaceutically accepted carrier;” Par. 0085: “inhalation”);
the method comprising:
using an analyzer (e.g., a spirometer; Par. 0129) to measure fractional nitric oxide concentrationin exhaled breath of the patient
indicating a positive efficacy of the therapy based on an amount of exhaled nitric oxide (Par. 0129)
Burch doesn’t expressly teaches:
using a point-of-care device to collect respective samples of exhaled breath from the patient respectively before initiation of the therapy and during the therapy;
using the analyzer (spirometer) to measure fractional nitric oxide (NO) concentration and hydrogen peroxide (H2O2) concentration in the respective samples of the exhaled breath before the initiation of the therapy and at various timepoints following the initiation of the therapy; and
indicating a positive efficacy of the therapy when the analyzer measures an increase in the fractional nitric oxide concentration and a decrease in the hydrogen peroxide concentration in the samples of the exhaled breath over time.
Burch also teaches that, in airways of the patient with primary ciliary dyskinesia, nitric oxide (NO) is depleted by infection in the airways and hydrogen peroxide (H2O2) is produced by inflammatory cells in the airways (Par. 0037). In other words, there is a low fractional nitric oxide concentration and a high hydrogen peroxide concentration in the airways of the patient with primary ciliary dyskinesia. The antioxidant agents administered by the therapy thus would serve as an antimicrobial function to reduce the infection and to react with the inflammatory cells so as to inhibit their growth (Pars. 0039-0041). Understandably, the therapy if successful would result in an increase in the fractional nitric oxide concentration and a decrease in the hydrogen peroxide concentration in the airways of the patient over time (because the infection has been reduced and growth of the inflammatory cells has been inhibited).
It would have been obvious to one ordinarily skilled in the art before the effective filing date of the present application to apply Burch teaching by using a point-of-care device to collect respective samples of exhaled breath from the patient respectively before initiation of the therapy and during the therapy; using the analyzer (spirometer) to measure fractional nitric oxide (NO) concentration and hydrogen peroxide (H2O2) concentration in the respective samples of the exhaled breath before the initiation of the therapy and at various timepoints following the initiation of the therapy; and indicating a positive efficacy of the therapy when the analyzer measures an increase in the fractional nitric oxide concentration and a decrease in the hydrogen peroxide concentration in the samples of the exhaled breath over time; simply because the therapy if successful would result in an increase in the fractional nitric oxide concentration and a decrease in the hydrogen peroxide concentration in the airways of the patient over time.
3. Burch as modified teaches the method of claim 1, but is silent about: wherein the one or more antioxidant agents is selected from a group consisting of N-acetylcysteine, Nacystelyn, N-isobutyrlcysteine, carbocisteine, procysteine, erdosteine, thioredoxin, 15d-PGJ2, CDDO-imidazolide, sulforaphane, chalcones, superoxide dismutase, ebselen, molecular hydrogen, celastrol, 2-thioxanthine, glutathione, vitamin A (retinol) β-carotenes, vitamin C (ascorbic acid), vitamin D (cholecalciferol), vitamin E (gamma and/or alpha tocopherol), lipo-glutathione (glutathione) and coenzyme Q (ubiquinone).
However, it has been held that optimization within prior art conditions or through routine experimentation is an obvious variation of a known structure, thus uninventive and unpatentable. In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). As for the present case, it appears that the one or more antioxidant agents may be any one or more of the antioxidant agents recited in the claim, or any other antioxidant agents, as long as they can serve as an antimicrobial function to reduce the infection and to react with the inflammatory cells so as to inhibit their growth in a patient with primary ciliary dyskinesia. Such an antimicrobial function of an antioxidant may be determined through routine experiments.
It would have been obvious to one ordinarily skilled in the art before the effective filing date of the present application to have the one or more antioxidant agents selected from a group consisting of N-acetylcysteine, Nacystelyn, N-isobutyrlcysteine, carbocisteine, procysteine, erdosteine, thioredoxin, 15d-PGJ2, CDDO-imidazolide, sulforaphane, chalcones, superoxide dismutase, ebselen, molecular hydrogen, celastrol, 2-thioxanthine, glutathione, vitamin A (retinol) β-carotenes, vitamin C (ascorbic acid), vitamin D (cholecalciferol), vitamin E (gamma and/or alpha tocopherol), lipo-glutathione (glutathione) and coenzyme Q (ubiquinone), or any other antioxidant agents, as long as they can serve as an antimicrobial function to reduce the infection and to react with the inflammatory cells so as to inhibit their growth in a patient with primary ciliary dyskinesia. Such an antimicrobial function of an antioxidant may be determined through routine experiments.
10. Burch as modified teaches the method of claim 3, wherein the therapy further comprises modulating airway pH in the patient’s airway by using a nebulizer to administer nebulized NaHCO3 to the patient, or a noninvasive positive-pressure ventilator without an endotracheal airway to augment alveolar ventilation of the patient (Burch pars. 0002, 0048, 0051, 0057, 0084. Also, see discussion above in claim 6).
12. (essentially equivalent to claim 1 + claim 6)
Burch as modified teaches a method of assessing efficacy of a therapy in a patient with primary ciliary dyskinesia, the therapy comprising modulating airway pH in the patient’s airway by using a nebulizer to administer nebulized NaHCO3 to the patient, or a noninvasive positive-pressure ventilator without an endotracheal airway to augment alveolar ventilation of the patient (See discussion above in claim 6),
the method comprising (See discussion above in claim 1):
using a point-of-care device to collect respective samples of exhaled breath from the patient respectively before initiation of the therapy and during the therapy;
using an analyzer to measure fractional nitric oxide concentration and hydrogen peroxide concentration in the respective samples of the exhaled breath before the initiation of the therapy and at various timepoints following the initiation of the therapy; and
indicating a positive efficacy of the therapy when the analyzer measures an increase in the fractional nitric oxide concentration and a decrease in the hydrogen peroxide concentration in the respective samples of the exhaled breath over time.
14 and 17-18 (essentially equivalent to claim 1 + claim 6 + claim 7).
Burch as modified teaches the claims (See discussions above in claims 1, 6 and 7).
20 (essentially equivalent to claim 1 + claim 6 + claim 11).
Burch as modified teaches the claim (See discussions above in claims 1, 6 and 11).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Nguyen (Wyn) Q. Ha whose telephone number is (571) 272-2863, email: nguyenq.ha@uspto.gov. The examiner can normally be reached Monday - Friday 8 am - 4:30 pm (Eastern Time).
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/Nguyen Q. Ha/Primary Examiner, Art Unit 2853 January 29, 2026