DETAILED ACTION
Claim Objections
Claims 2, 4, 6 and 12 are objected to because of administrative errors. Going forward with examination, the claims are interpreted to be:
--1. A method of assessing
measuring a fractional nitric oxide concentration and a hydrogen peroxide concentration via an analyzer in a sample from the patient before
administering the antioxidant therapy to the patient, wherein an increase in the 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.--
--4. The method of claim 1, wherein the antioxidant therapy is administered by one or more of routes of administration selected from the group consisting of oral, inhalation, intravenous, subcutaneous, sublingual, and transdermal.--
--6. A method of treating primary ciliary dyskinesia in a patient in need thereof comprising:
administering a therapy to the patient that increases airway pH in the patient's airway, wherein the therapy is administered using a nebulizer or a noninvasive positive-pressure ventilator without an endotracheal airway to augment alveolar ventilation of the patient, and
administering the therapy having an antioxidant that is selected from the 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) ß- carotenes, vitamin C (ascorbic acid), vitamin D (cholecalciferol), vitamin E (gamma tocopherol), lipo-glutathione (glutathione) and coenzyme Q (ubiquinone).
--12. A method of assessing
measuring a fractional nitric oxide concentration and a hydrogen peroxide concentration in
administering a therapy that increases
wherein the treatment is efficacious when the measuring shows an increase in fractional nitric oxide concentration and a decrease in hydrogen peroxide concentration in the exhaled breath of the patient over time.--
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, 3, 5, 12 and 15-20 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 “administering the antioxidant therapy to the patient…” The method, as claimed, is a judicial exception because it appears merely a mental process practiced mentally and not integrated into any of the physical statutory patentable categories: process, machine, manufacture, or composition of matter. The claim fails to recite how “administering the antioxidant therapy to the patient…” is performed physically (similarly, “a carpet configured to fly”). One would not be able to physically practice claim 1. Dependent claims 3 and 5 also 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).
Similarly, independent claim 12 essentially recites a method of assessing efficacy of treatment of primary ciliary dyskinesia in a patient, comprising “measuring a fractional nitric oxide concentration…“ and “administering a therapy…” The method, as claimed, is a judicial exception because it fails to recite how the measuring and administering are performed physically. One would not be able to physically practice claim 12. Dependent claims 15-20 also fail to include any additional elements that are sufficient to amount to significantly more than the judicial exception, and have a practical application.
Going forward with examination, at least claims 1, 4, and 12 are interpreted to be:
--1. A method of assessing
measuring a fractional nitric oxide concentration and a hydrogen peroxide concentration via an analyzer in a sample from the patient before
administering the antioxidant therapy to the patient, wherein an increase in the 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, and wherein the antioxidant therapy is administered by one or more of routes of administration selected from the group consisting of oral, inhalation, intravenous, subcutaneous, sublingual, and transdermal.--
--4 (Canceled).
--12. A method of assessing
measuring, via an analyzer, a fractional nitric oxide concentration and a hydrogen peroxide concentration in , wherein the exhaled breath of the patient is collected via a point-of-care device,
administering a therapy that increases wherein the antioxidant therapy is administered by one or more of routes of administration selected from the group consisting of oral, inhalation, intravenous, subcutaneous, sublingual, and transdermal, and
wherein the treatment is efficacious when the measuring shows an increase in fractional nitric oxide concentration and a decrease in hydrogen peroxide concentration in the exhaled breath of the patient over time.--
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.
All pending claims 1, 3, 5-6, 8, 10-12, 15-20 and 23 (as are interpreted above) are rejected under 35 U.S.C. 103 as being unpatentable over Burch (US 2019/0231686 A1).
1. Burch teaches a method of assessing efficacy of an antioxidant therapy in a patient with primary ciliary dyskinesia (The therapy comprises administering one or more antioxidants to protect against oxidative stress and to reduce production of pro-inflammatory cytokines and/or other markers of inflammation; Pars.0041, 0059; Pars. 0049, 0051: “The invention described here can be used to prevent deterioration of lung function…In addition to treatment of cystic fibrosis, the invention can be used to treat other mucosal surface disease such as but not limited to…primary ciliary dyskinesia [PCD]… By “treating” or “managing” it is meant improving, preventing worsening of, and/or alleviating symptoms of a mucosal surface disease such as but not limited to…primary ciliary dyskinesia [PCD];” Par. 0088: “One aspect of the current invention is a method for treatment or improvement of pulmonary conditions in cystic fibrosis, asthma, primary ciliary dyskinesia [PCD]”), the method comprising:
measuring a fractional nitric oxide (NO) concentration via an analyzer (which is part of a spirometry test equipment shown in Fig. 1, reproduced below, from an article by Cleveland Clinic provided herein with this Office action) in a sample from the patient, wherein the sample from the patient is collected from exhaled breath of the patient using a point-of-care device (which may be a nose clip of the spirometry test equipment shown in Fig. 1 below; Burch Par. 0129: “The amount of exhaled nitric oxide [NO]…can be measured to determine efficacy of the formulation/antioxidant. In addition, forced expiratory volume per one second (FEV1) will be measured via spirometry…”), and
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administering the antioxidant therapy to the patient (via a nebulizer; Abstract; Pars. 0066-0067, 0084) to determine efficacy of the antioxidant (by measuring the amount of exhaled nitric oxide [NO] concentration as discussed above; Par. 129), wherein an amount of exhaled nitric oxide (NO) concentration measured in the exhaled breath of the patient can be used to determine efficacy of the antioxidant (as discussed above; Par. 0129; See Note 1 below), and wherein the antioxidant therapy is administered by one or more of routes of administration selected from the group consisting of oral, inhalation (using the nebulizer, as discussed above ; Par. 0084), intravenous, subcutaneous, sublingual, and transdermal (See Note 1 below).
Note 1: Burch teaches a method of assessing efficacy of an antioxidant therapy in a patient with cystic fibrosis (CF) and/or other infectious or inflammatory lung disease or mucosal surface condition in a patient (Abstract). The other infectious or inflammatory lung disease may include primary ciliary dyskinesia or PCD (Pars.0041, 0059, 0049, 0051, 0088).
The therapy includes using a drug formulation (an antioxidant) with beneficial and/or synergistic effects among ingredients which comprise specific formulation (described in Burch paragraphs 0038-0139 for example). The antioxidant is expected to restore immune defenses, restore extended hydration, and to help raise airway surface liquid pH in the airways of the patient (Pars. 0002, 0048, 0051, 0057, 0125, 0128; Burch claim 1).
When used to treat a lung disease (e.g., CF or PCD), a measured amount of the antioxidant is delivered/administered to airways of the patient as an inhaled dose by a nebulizer (Abstract; Par. 0084).
Burch further teaches that “Hydrogen peroxide (H2O2) is also produced by inflammatory cells in the CF conducting airways…Various exocrine secretions of patients with CF are deficient in…NO…, which is commonly depleted by infection (Par. 0037).”
Understandably, in airways of a patient with cystic fibrosis (CF) or primary ciliary dyskinesia (PCD), hydrogen peroxide (H2O2) is produced by inflammatory cells, and nitric oxide (NO) is depleted by infection (Par. 0037). In other words, there is a high hydrogen peroxide (H2O2) concentration and a low fractional nitric oxide (NO) concentration in the airways of a patient with cystic fibrosis (CF) or primary ciliary dyskinesia (PCD). Obviously, the therapy if successful would result in a decrease in the hydrogen peroxide (H2O2) concentration and an increase in the fractional nitric oxide (NO) concentration in the airways of the patient over time (because growth of inflammatory cells has been inhibited and infection has been reduced).
So, as shown in fig. 1 above, spirometry test equipment, having a nose clip, is used to collect a sample in exhaled breath of the patient. The spirometry test equipment, also having an analyzer, is used to measure an amount/concentration of exhaled nitric oxide (NO) in the sample in exhaled breath of the patient to assess the efficacy of the therapy (Par. 0129).
Burch doesn’t expressly teach: measuring the fractional nitric oxide (NO) concentration and a hydrogen peroxide (H2O2) concentration via the analyzer in the sample from the patient before initiation of, and at various timepoints following the initiation of, the therapy, wherein an increase in fractional nitric oxide (NO) concentration and a decrease in hydrogen peroxide (H2O2) concentration in the sample from the patient over time indicate positive efficacy of the antioxidant therapy.
However, as discussed above in Note 1, Burch teaches “Hydrogen peroxide (H2O2) is also produced by inflammatory cells in the CF conducting airways…Various exocrine secretions of patients with CF are deficient in…NO…, which is commonly depleted by infection (Par. 0037).” Again, understandably, in airways of a patient with cystic fibrosis (CF) or primary ciliary dyskinesia (PCD), hydrogen peroxide (H2O2) is produced by inflammatory cells, and nitric oxide (NO) is depleted by infection (Par. 0037). In other words, there is high hydrogen peroxide (H2O2) concentration and a low fractional nitric oxide (NO) concentration in the airways of a patient with cystic fibrosis (CF) or primary ciliary dyskinesia (PCD).
It would have been obvious to one ordinarily skilled in the art before the effective filing date of the present application to apply Burch disclosure by measuring the fractional nitric oxide (NO) concentration and a hydrogen peroxide (H2O2) concentration via the analyzer in the sample from the patient before initiation of, and at various timepoints following the initiation of, the therapy, wherein an increase in fractional nitric oxide (NO) concentration and a decrease in hydrogen peroxide (H2O2) concentration in the sample from the patient over time indicate positive efficacy of the antioxidant therapy (as claimed), simply because the therapy if successful would result in an increase in the fractional nitric oxide (NO) concentration and a decrease in the hydrogen peroxide (H2O2) concentration in the airways of the patient over time (as infection has been reduced and growth of inflammatory cells has been inhibited).
3. Burch as modified teaches the method of claim 1, but is silent about: wherein the antioxidant therapy (with the one or more antioxidants) 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 antioxidants may be any one or more of the antioxidants recited in the claim, or any other antioxidants, regardless if they are known or believed to serve as an antimicrobial function to reduce infection and to react with inflammatory cells in airways of a patient so as to inhibit their growth. Such an antimicrobial function of an antioxidant may be determined through routine experiments (and tested using spirometry taught by Burch for example).
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 antioxidants 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 antioxidants, regardless if they are known or believed to serve as an antimicrobial function to reduce infection and to react with inflammatory cells in airways of a patient so as to inhibit their growth. Such an antimicrobial function of an antioxidant may be determined through routine experiments (and tested using spirometry taught by Burch for example).
5. Burch as modified teaches the method of claim 1, wherein the primary ciliary dyskinesia is exacerbated by one or more of asthma, exposure to cigarette smoke (as 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 the claim appears to recite an inherent feature of PCD and/or a natural phenomenon related to PCD, thus may not be patentable).
6 (essentially equivalent to claims 1+ 3).
Burch as modified teaches a method of treating primary ciliary dyskinesia in a patient in need thereof comprising:
administering a therapy to the patient that increases airway pH in the patient's airway, wherein the therapy is administered using a nebulizer or a noninvasive positive-pressure ventilator without an endotracheal airway to augment alveolar ventilation of the patient (Note that, similar to the discussion above in claim 1 Note 1, the therapy comprises administering one or more antioxidants to the patient by using a nebulizer. The one or more antioxidants is expected to restore immune defenses, restore extended hydration, and to help raise airway surface liquid pH in the airways of the patient – Pars. 0002, 0048, 0051, 0057, 0125, 0128; Burch claim 1), and
administering the therapy having an antioxidant that is selected from the 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) ß- carotenes, vitamin C (ascorbic acid), vitamin D (cholecalciferol), vitamin E (gamma tocopherol), lipo-glutathione (glutathione) and coenzyme Q (ubiquinone) (or any other antioxidants, regardless if they are known or believed to serve as an antimicrobial function to reduce infection and to react with the inflammatory cells in airways of a patient so as to inhibit their growth. Such an antimicrobial function of an antioxidant may be determined through routine experiments and tested using spirometry taught by Burch for example. See similar discussion above in claim 3).
8. Burch as modified teaches the method of claim 6, wherein the therapy is nebulized NaHCO₃ (or any other antioxidant. See similar discussion above in claim 3).
10. Burch as modified teaches the method of claim 1, further comprising administering a therapy to the patient that increases airway pH in the patient's airway, wherein the therapy is administered using a nebulizer or a noninvasive positive-pressure ventilator without an endotracheal airway to augment alveolar ventilation of the patient (as discussed above in claim 1, Note 1 or claim 6).
11. Burch as modified teaches 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 (See discussion above in claim 5), 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 (essentially equivalent to claim 1).
Burch as modified teaches a method of assessing the efficacy of treatment of primary ciliary dyskinesia in a patient, comprising:
measuring, via an analyzer (of a spirometry test equipment shown in fig. 1 above), a fractional nitric oxide (NO) concentration and a hydrogen peroxide (H2O2) concentration in exhaled breath of the patient before initiation of treatment and at various timepoints following the initiation of treatment (See discussion above in claim 1), wherein the exhaled breath of the patient is collected via a point-of-care device (which may be a nose clip of a spirometry test equipment shown in fig. 1 above. See discussion above in claim 1),
administering a therapy that increases airway pH, wherein the antioxidant therapy is administered by one or more of routes of administration selected from the group consisting of oral, inhalation (See discussion above in claim 1), intravenous, subcutaneous, sublingual, and transdermal, and
wherein the treatment is efficacious when the measuring shows an increase in fractional nitric oxide (NO) concentration and a decrease in hydrogen peroxide (H2O2) concentration in the exhaled breath of the patient over time (See discussion above in claim 1).
15. Burch as modified teaches the method of claim 12, wherein the therapy is nebulized NaHCO₃ (or any other antioxidant. See discussion above in claim 3).
16. Burch as modified teaches the method of claim 12, wherein the therapy that modulates airway pH is administered using noninvasive ventilation (e.g., by mean of a nebulizer. See discussion above in claim 1; Abstract; Par. 0084).
17. Burch as modified teaches the method of claim 12, further comprising administering one or more of an antioxidant (See discussion above in claim 1).
18. Burch as modified teaches the method of claim 17, where in the antioxidant is selected from the 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) ß- carotenes, vitamin C (ascorbic acid), vitamin D (cholecalciferol), vitamin E (gamma tocopherol), lipo-glutathione (glutathione) and coenzyme Q (ubiquinone) (See discussion above in claim 3).
19. Burch as modified teaches the method of claim 17, wherein the antioxidant therapy is administered by one or more of routes of administration selected from the group consisting of oral, , inhalation (See discussion above in claim 1; Par. 0084), intravenous, subcutaneous, sublingual, and transdermal.
20. Burch as modified teaches the method of claim 12, wherein the primary ciliary dyskinesia is exacerbated by one or more of asthma, exposure to cigarette smoke (See discussion above in claim 5), 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.
23 (essentially equivalent to claim 1).
Burch as modified teaches a method of measuring a fractional nitric oxide (NO) concentration and a hydrogen peroxide (H2O2) concentration in a sample comprising:
collecting the sample from a subject (e.g., a patient) using a point-of-care-device (which may be a nose clip of a spirometry test equipment shown in fig. 1 above; Burch Par. 0129. See discussion above in claim 1), wherein the sample is an exhaled breath (of the patient), and the subject (patient) has primary ciliary dyskinesia (See discussion above in claim 1); and
measuring the fractional nitric oxide (NO) concentration and the hydrogen peroxide (H2O2) concentration in the sample via an analyzer (of a spirometry test equipment shown in fig. 1 above, so as to assess efficacy of an antioxidant therapy in the patient for example. See discussion above in claim 1).
Response to Arguments
Applicant's arguments filed as a Remarks on May 8, 2026 have been fully considered but they are not persuasive with respect to the claim rejections. Contrary to applicant’s arguments, Burch indeed teaches administering an antioxidant therapy to treat PCD. Burch indeed addresses presences of nitric oxide (NO) concentration and hydrogen peroxide (H2O2) concentration in airways of a patient having PCD. Burch also teaches and/or suggests that an increase in fractional nitric oxide (NO) concentration and a decrease in the hydrogen peroxide (H2O2) concentration in airways of a patient having PCD would indicate efficacy of the antioxidant therapy to treat the PCD.
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.
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 May 21, 2026
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