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 .
Election/Restrictions
Claims 1-19 are withdrawn from further consideration and cancelled pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 05/21/2026.
See attached interview summary for further details about the response to the selection of the election/restriction.
Information Disclosure Statement
The information disclosure statements filed on 02/20/2023, 10/01/2024, and 08/19/2025 have been received and fully considered.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
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.
Claims 20-22 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding claim 20, the metes and bounds of the limitation “generated NO is at a concentration of 90-100%” because there is no relativity provided regarding the concentration (i.e. concentration in solution, concentration at the time the reaction happens, concentration of NO once it is delivered to the patient). The system merely may use 100% stock NO which then needs to be diluted to 80 ppm when mixed with air (Specification at Paragraph 0080). Applicant shows that the maximum concentration achieved of NO generated would be 80ppm, not an integer of 1 (See Tables 2 and 3 at Paragraph 0151). Applicant also discusses that from a single reaction, the dose produced can be tuned from about 2ppm to about 40ppm of NO in air or O2 for 1 to 72 hours (Paragraph 0066). Thus it is examiner’s position it is unclear what Applicant means be the generated NO has a concentration of about 90% to 100%. For the sake of examination, examiner is interpreting the concentration of generated NO being about 90% to 100% to mean that the generated NO is undiluted.
Applicant may obviate this rejection by stating the concentration is volume of generated NO/total volume air (Paragraph 0066 appears to contemplate the 100% generated NO being mixed with air).
Claim 21 depends from claim 20 and is also rejected under 112(b) by virtue of its dependency.
Regarding claim 21, it is unclear whether the further limitations for the method of rection are intended to require the RSNO reaction in claim 20, or if the claim is satisfied with the disclosure of the nitrite and electron donor compound in an aqueous solution.
Regarding claim 22, the same limitation of “generated NO is at a concentration of about 90%-100%” is present and thus is unclear for at least the reasons mentioned in claim 20. This rejection may be obviated in the same manner as claim 20.
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 20-21 are rejected under 35 U.S.C. 103 as being unpatentable over WO2020074957A1 to Tamarkin et al. (hereinafter “Tamarkin”) in view of US20180071467A1 to Fine et al. (hereinafter “Fine”).
Regarding claim 20, Tamarkin discloses a method for generating NO for inhaled therapy (See Fig. 1 for the general system/reaction vessel; Page 14 lines 14-18 disclose the system is used to release NO gas; Page 13 lines 14-17 disclose the system can be an inhaler device for respiratory therapy) comprising:
(a) reacting a nitrite and an electron donor compound in an aqueous solution (Page 5 lines 8-11, Page 11 lines 17-20; Page 15 lines 8-12, 33-35, Page 17, lines 16-19 disclose a container comprising an aqueous solution having nitrite and an acid such as ascorbic acid (nitrite and an electron donor as seen in Applicant specification at Paragraph 0054 describes NO+ ions rapidly reduce to NO in the presence of electron donor compounds. In a first method for generation NO, ascorbic acid is used as an electron donor compound to reduce the nitrosonium ion to NO. This NO can then be used as a source of INO therapy)), wherein the reaction is performed under anaerobic conditions at a pH of about 3 to 3.5 (Fig. 7 block 720 Page 32 lines 12-16 disclose the system is made to be airtight (anaerobic) (Pages 12-13); Page 15 lines 8-14 disclose the solution of nitrites and acids mixing in an aqueous solution may have a pH of about 3.2); or
(b) reacting a nitrite and a thiol (RSH) in an aqueous solution, wherein the reaction is performed under anaerobic conditions in the absence of light at a first pH of about 1 to 4.5, wherein the reaction produces RSNO and at least a portion of the RSNO decomposes to NO (Due to the use of “or” the claim is satisfied when only the former limitation is disclosed);
wherein the nitrite is selected from the group consisting of sodium nitrite (Page 15 lines 21-23 disclose using sodium nitrite or other salts of nitrites), potassium nitrite calcium nitrite, zinc nitrite, copper nitrite, rubidium nitrite, strontium nitrite, and barium nitrite; and wherein the generated NO has a concentration of about 90% to 100% (Page 20 lines 18-32 disclose the generated NO concentration can be at least about 2 ppm for a timer period of 24 hours or the concentration can be at least about 20 ppm for a period of 12 hours, or an average of 20ppm/hour for a period of 12 hours).
Tamarkin does not disclose wherein the generated NO has a concentration of about 90% to 100%. However, Fine teaches a system and method for portable nitric oxide delivery which generates NO with a concentration between about 90%-100% (Paragraph 0067 discloses “In this novel system, when a nitric oxide-releasing agent such as N.sub.2O.sub.4 or NTO is vaporized, it is transitioned from a liquid to gaseous NO.sub.2, diluted with ambient air and passed through an ascorbic acid (vitamin C) cylinder where it is converted to ultra-pure NO gas for delivery to the patient. The ascorbic acid, an antioxidant, safely strips one atom of oxygen from the NO.sub.2 to generate ultrapure NO.”).
Therefore, it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to modify the system of Tamarkin to generate NO with a concentration of about 90%-100%, as taught by Fine, in order to provide a patient with pure NO to reduce the risk of NO2 ventilation/perfusion inequality (Paragraph 0067).
Regarding claim 21, Tamarkin in view of Fine discloses the method of claim 21. Claim 22 is further rejected as being drawn to an unelected subgroup.
Reasons for not making a prior art rejection
Claim 22 is rejected under 112(b) indefinites as outlined in the previous section.
Regarding claim 22, the closest prior art combination of record, Tamarkin in view of Fine and US20170216550A1 to Meyerhoff et al. (hereinafter “Meyerhoff”), discloses a method of treating a patient in need of inhaled NO (Tamarkin See Fig. 1 for the general system/reaction vessel; Page 14 lines 14-18 disclose the system is used to release NO gas; Page 13 lines 14-17 disclose the system can be an inhaler device for respiratory therapy), comprising:
reacting in a reaction vessel (Tamarkin Fig. 1 pressure-resistant container 102) a nitrite and an electron donor compound in an aqueous acidic solution, wherein the reaction is performed under anaerobic conditions at a pH of about 3 to 5 (Tamarkin Page 5 lines 8-11, Page 11 lines 17-20; Page 15 lines 8-12, 33-35, Page 17, lines 16-19 disclose a container comprising an aqueous solution having nitrite and an acid such as ascorbic acid (nitrite and an electron donor as seen in Applicant specification at Paragraph 0054 describes NO+ ions rapidly reduce to NO in the presence of electron donor compounds. In a first method for generation NO, ascorbic acid is used as an electron donor compound to reduce the nitrosonium ion to NO. This NO can then be used as a source of INO therapy; Fig. 7 block 720 Page 32 lines 12-16 disclose the system is made to be airtight (anaerobic) (Pages 12-13); Page 15 lines 8-14 disclose the solution of nitrites and acids mixing in an aqueous solution may have a pH of about 3.2) to form 90% to 100% concentrated and pressurized NO (Fine Paragraph 0067 “In this novel system, when a nitric oxide-releasing agent such as N.sub.2O.sub.4 or NTO is vaporized, it is transitioned from a liquid to gaseous NO.sub.2, diluted with ambient air and passed through an ascorbic acid (vitamin C) cylinder where it is converted to ultra-pure NO gas for delivery to the patient. The ascorbic acid, an antioxidant, safely strips one atom of oxygen from the NO.sub.2 to generate ultrapure NO.”), removing the pressurized NO from the vessel to a NO storage system (Meyerhoff Fig. 2 housing 56; Paragraph 0068-0069 discloses the separator housing houses the generated NO stream between two spaces 60,62; Paragraph 0069 discloses space 60 has a mixture of N2/NO diffuses across NO permeable material into space 62), diluting the NO to 80 ppm or less with oxygen in a mixing chamber (Meyerhoff Paragraph 0084 discloses the generated NO may be in a concentration range of 10 to 70 ppm),
where the NO is delivered to the oxygen at a velocity to prevent NO2 formation, and providing, via a tube, the diluted NO to the patient for inhalation (Meyerhoff Fig. 2 delivery conduit 72 connected with housing outlet 66’; Paragraph 0059 discloses the delivery conduit may be a hose, tube or the like that can transport output gas stream to a patient; Paragraphs 0086 and 0110 disclose sensor 76 is used to adjust flow rates of the gases and sensor 76 is used to determine if the level of NO2 is too high; Examiner notes the system of Tamarkin would be modified by Meyerhoff to include the above additions to the system to provide adjusted concentrations of NO gas to provide a suitable does to a patient to treat a selected medical condition (Meyerhoff Col. 3 lines 13-32)).
Tamarkin in view of Meyerhoff does not disclose “wherein the reaction vessel comprises an upper liquid reservoir and a lower chemical reservoir separated by a port plugged with a plunger, and wherein the reaction is initiated by connecting the two chambers”. Nor would it have been obvious to make such modifications. Modified Tamarkin has a system where the reaction vessel is separated into two chambers which are separated by a nitric oxide permeable membrane (Meyerhoff Fig. 2 housing 56; Paragraph 0068-0069 discloses the separator housing houses the generated NO stream between two spaces 60,62; Paragraph 0069 discloses space 60 has a mixture of N2/NO diffuses across NO permeable material into space 62). Thus modified Tamarkin’s reaction is initiated before separation of the reagents and the barrier to separate the products is done via the membrane. The osmosis membrane is a critical piece for providing the patient with NO gas, and replacing it with a plunger would require a complete redesign of the system and destroy functionality of the modified system.
Examiner notes that WO2008031182A1 to Pacheco et al. (hereinafter “Pacheco”) discloses a plunger system for mixing reactants, see Fig. 2. As discussed above, it would not have been obvious to modify Tamarkin with a plunger system. Furthermore, Pacheco is intended for topical application of NO gel for wound healing, and would not have been obvious for modify with a downstream chamber for mixing oxygen.
Absent any new prior art made of record, it would not have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to make such modifications.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure: US-20180243527-A1 to Zapol; US-20050076907-A1 to Stenzler; US-20150290417-A1 to Stenzler; US-20140275901-A1 to Flanagan; US-20140216452-A1 to Miller; US-20130330244-A1 to Balaban; US-20130231591-A1 to Riggs; US-20120114702-A1 to Watson; US-20110259325-A1 to Fine; US-20100303918-A1 to Watson; US-20080053432-A1 to Larsson; US-20060180147-A1 to Roundbehler; US-10682486-B1 to Moon; US-20190069820-A1 to Chen; US-20190314595-A1 to Dube; US-20200361772-A1 to Hall; and US-5827420-A to Shirazi.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to TYLER RAUBENSTRAW whose telephone number is (571)272-0662. The examiner can normally be reached Monday-Friday 7:30-5:30.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, BRANDY LEE can be reached at 571-270-3525. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/TYLER A RAUBENSTRAW/Examiner, Art Unit 3785
/BRADLEY H PHILIPS/Primary Examiner, Art Unit 3799
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