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 .
Priority
This application is a national stage entry of PCT/GB2021/050935, filed 4/19/2021. This application claims foreign priority to GB2005987.9, filed 4/23/2020 and GB2008288.9, filed 6/2/2020.
Information Disclosure Statement
The IDS filed on 7/11/2025 has been considered. See the attached PTO 1449 form.
Claim Status
Receipt of Remarks/Amendments filed on 7/10/25 is acknowledged. Claims 11-13 and 15-26 are currently pending. Claims 15-19 are withdrawn. Accordingly, claims 11-13 and 20-26 are currently under examination.
Rejection(s) not reiterated from the previous Office Action are hereby withdrawn. The following rejections are either reiterated or newly applied. They constitute the complete set of rejections presently being applied to the instant application.
Withdrawn Rejections/Objections
The nonstatutory double patenting over copending Application No. 17/920,099 has been withdrawn due to filing of a Terminal Disclaimer.
The claim objections made in the previous office action have been withdrawn due to appropriate claim amendments.
The 112(a) rejection made in the previous officiation action has been withdrawn due to appropriate claim amendments.
The 112(b) rejection made in the previous officiation action has been withdrawn due to appropriate claim amendments and cancelling of claim 14.
Terminal Disclaimer
The terminal disclaimer filed on 7/10/2025 disclaiming the terminal portion of any patent granted on this application which would extend beyond the expiration date of any patent granted on application number 17920099 has been reviewed and is accepted. The terminal disclaimer has been recorded.
New/Maintained Claim Objection(s) / Rejection(s)
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 11, 13, 20-22 are rejected under 35 U.S.C. 103 as being unpatentable over Tawashi (US 5,648,101; Jul. 15, 1997) in view of Sanotize (Sanotize Research and Development Corp., April 22, 2020) and Rahimpour (Drug Discovery Today, Volume 19, Number 5, May 2014).
Tawashi throughout the reference teaches method of delivering nitric oxide to a desired situs on or in the body of humans. Specifically, the invention comprises methods and means for delivering the compositions of the invention to a desired situs on or in the body of humans. The composition is adapted to release or liberate nitric oxide at or adjacent a desired situs on or in the body of humans. (see: Abstract; Summary of Invention). Tawashi discloses the nitric oxide releasing composition comprises sodium nitrite (nitrite salt), citric acid (proton source) and mannitol (organic polyol as recited in claim 11 and 14) (see: Examples 1 and 2). Mannitol taught by Tawashi reads on the specific sugar alcohol recited in claims 11, 20 and 21. Tawashi also teaches administering the composition in the form of dry powder inhalation or aerosol metered dose inhaler wherein the nitric oxide is release into the respiratory tract and lungs (Example 11 and 12). Example 11 and 12 of Tawashi disclose the nitric oxide releasing composition comprises sodium nitrite (nitrite salt) and citric acid (proton source).
The teachings of Tawashi have been set forth above.
While Tawashi teaches mannitol in the tablet composition disclosed in examples 1 and 2, Tawashi does not teach composition in the form of inhaler, which is delivered to the lungs, comprises mannitol. However, Rahimpour cures this deficiency.
Rahimpour teaches alternative carriers in dry powder inhaler formulations. Rahimpour teaches use of mannitol as pharmaceutical excipient/carrier in dry powder inhalers. Mannitol is less hygroscopic than lactose and gives a suitable sweet aftertaste, which has a benefit to patients confirming them that a dose has been properly administered. (see e.g., Mannitol section; pg. 620; Abstract).
Tawashi does not teach a method of treating an infection arising from SARS-COV-2 or COVID-19 with the nitric oxide generating composition. However, Sanotize cures this deficiency.
Sanotize discloses that new tests conducted by the institute for Antiviral Research at Utah State University confirm nitric oxide releasing solution inactivated more than 99.9% of SARS-COV-2, the virus that causes COVID-19 (see: entire document).
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to combine the teachings of Tawashi and Rahimpour and incorporate mannitol in the dry powder inhaler taught by Tawashi. One would have been motivated to do so because, as discussed supra, Rahimpour teaches use of mannitol as pharmaceutical excipient/carrier in dry powder inhalers wherein mannitol is less hygroscopic than lactose and gives a suitable sweet aftertaste, which has a benefit to patients confirming them that a dose has been properly administered. Tawashi in its example 11 discloses use of lactose in the dry powder inhaler and Rahimpour provides the motivation to include mannitol which offers more benefits. Thus, inclusion of mannitol in the inhaler formulation which is delivered to the lungs would have been prima facie obvious to one skilled in the art.
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to combine the teachings of Tawashi and Sanotize and utilize the nitric oxide releasing composition of Tawashi to treat SARS-COV-2 or COVID-19 as suggested by Sanotize. Tawashi teaches that nitric oxide can be applied and used clinically in the treatment of a variety of diseases (col. 2, line 23-26). Sanotize discloses that nitric oxide releasing solution inactivated more than 99.9% of SARS-COV-2, the virus that causes COVID-19. Therefore, one skilled in the art would have been highly motivated to utilize the nitric oxide releasing composition of Tawashi to treat SARS-COV-2 or COVID-19.
Further, Sanotize teaches nitric oxide having an antiviral effect and therefore, it would have been obvious to one skilled in the art to determine an antivirally effective amount to treat the viral infection during routine experimentation. Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here 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).
From the combined teaching of the cited references, one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention, as a whole, would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made.
Claim 12 is rejected under 35 U.S.C. 103 as being unpatentable over Tawashi (US 5,648,101; Jul. 15, 1997) in view of Sanotize (Sanotize Research and Development Corp., April 22, 2020) and Rahimpour (Drug Discovery Today, Volume 19, Number 5, May 2014) as applied to claims 11, 13, 20-22 above, and further in view of Mirazimi (Journal of Virology, Feb. 2005, p. 1966-1969).
The teachings of Tawashi, Sanotize and Rahimpour have been set forth above.
Tawashi, Sanotize and Rahimpour do not teach a method of treating an infection arising from SARS-COV and SARS with the nitric oxide generating composition. However, Mirazimi cures this deficiency.
Mirazimi teaches that nitric oxide significantly inhibited the replication cycle of SARS-COV and severe acute respiratory syndrome (SARS) which arises from this type of coronavirus. The results demonstrated that nitric oxide inhibits the replication cycle of SARS COV, most probably during the early steps of infection, suggesting that the production of nitric oxide results in an antiviral effect. (see: abstract; p. 1966-left col., p. 1967-right col.; entire document).
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to combine the teachings of Tawashi and Mirazimi and utilize the nitric oxide releasing composition of Tawashi to treat SARS-COV and SARS as suggested by Mirazimi. Tawashi teaches that nitric oxide can be applied and used clinically in the treatment of a variety of diseases (col. 2, line 23-26). As discussed supra, Mirazimi teaches that nitric oxide significantly inhibited the replication cycle of SARS-COV and severe acute respiratory syndrome (SARS) which arises from this coronavirus. The results demonstrated that nitric oxide inhibits the replication cycle of SARS COV, most probably during the early steps of infection, suggesting that the production of nitric oxide results in an antiviral effect. Therefore, one skilled in the art would have been highly motivated to utilize the nitric oxide releasing composition of Tawashi to treat SARS-COV and SARS.
From the combined teaching of the cited references, one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention, as a whole, would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made.
Claims 23-26 are rejected under 35 U.S.C. 103 as being unpatentable over Tawashi (US 5,648,101; Jul. 15, 1997) in view of Sanotize (Sanotize Research and Development Corp., April 22, 2020) and Rahimpour (Drug Discovery Today, Volume 19, Number 5, May 2014) as applied to claims 11, 13, 20-22 above and further in view of Godara (Lung India, vol 28, issue 4, Oct. 2011), ADM (Archer Daniels Midland Company, Safety Data Sheet, May 2019) and Rai (Respiratory Physiology and Neurobiology 257 (2018) 51-54).
The teachings of Tawashi, Sanotize and Rahimpour have been set forth above.
Tawashi, Sanotize and Rahimpour do not teach wherein the organic acid (e.g., citric acid) is buffered to a higher pH than exhibited by an aqueous solution of the acid at the same concentration as required in claims 23-26. However, Godara, ADM and Rai cure this deficiency.
ADM discloses that based on the low pH of citric acid, inhalation of citric acid would be expected to cause irritation to the respiratory tract, resulting in a higher cough response. (see Entire document).
Godara discloses impact of inhalation therapy on oral health. Low pH is a risk factor for demineralization of the tooth. It has been found that the low pH may be due to the use of the inhaler. There was a significant decrease in the salivary pH to below the critical value of 5.5 for enamel demineralization after 30 mins following their use. (see: Abstract; Pathophysiology; Entire document).
Rai teaches the effect of pH on citric acid cough response. Inhalation of citric acid solution were administered to subjects. The pH of the solution altered by the addition of sodium bicarbonate to 2, 5 and 6 and total number of cough elicited was recorded for each inhalation. Cough response from inhalation of citric acid solution with a pH of 6 was the lowest. (see: Abstract; Results; Entire document).
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to combine the teachings of the above cited references and buffer the citric acid taught by Tawashi to a higher pH than exhibited by an aqueous solution of the acid at the same concentration as required in claims 23-26. One would have been motivated to do so because the combination of ADM, Godara and Rai teach the low pH of citric acid causes adverse effect such as irritation to the respiratory tract, resulting in a higher cough response, and demineralization of the tooth. As discussed supra, Rai teaches citric acid solution having pH of 6 had lowest cough response and Godara teaches salivary pH below 5.5 causes demineralization of enamel. Thus, it would have been obvious to one skilled in the art to buffer the pH of citric acid to a pH of around 6 as this pH value is suggested to have least adverse effects in the prior art.
From the combined teaching of the cited references, one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention, as a whole, would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made.
Response to Arguments
Applicant argued the suggested composition of Tawashi is a tablet formulation for delivery to the gastrointestinal tract based on examples 1-2 and amended claim 11 requires administering to lungs of human or animal subject. Examples 11-12 are inhaler formulations but Tawashi fails to teach including mannitol in these inhaler formulations.
In response, the examiner respectfully draws applicant’s attention to the new 103 rejection over Tawashi in view of Sanotize and Rahimpour wherein Rahimpour renders obvious the inclusion of mannitol in the inhaler formulation of Tawashi. This new rejection is prompted by applicant’s amendments to the claims which only now require the claimed step of administering to a/the lung of a human or animal subject.
Applicant argued that there’s no motivation to combine Tawashi with the other cited references because Tawashi’s suggested composition is a tablet for delivery to GI tract and no skilled artisan developing formulation for delivery to lungs would look to a tablet formulation.
In response, as discussed supra, the examiner respectfully draws applicant’s attention to the new 103 rejection over Tawashi in view of Sanotize and Rahimpour wherein Tawashi teaches an inhaler formulation delivered to the lungs and Rahimpour renders obvious the inclusion of mannitol in the inhaler formulation of Tawashi. Tawashi teaches that nitric oxide can be applied and used clinically in the treatment of a variety of diseases (col. 2, line 23-26). Sanotize discloses that nitric oxide releasing solution inactivated more than 99.9% of SARS-COV-2, the virus that causes COVID-19. Therefore, one skilled in the art would have been motivated to utilize the nitric oxide releasing composition of Tawashi which is delivered to the lungs to treat SARS-COV-2 or COVID-19.
Applicant argued that Sanotize merely describes that the NORS of Sanotize inactivates SARS-COV2 but Sanotize fails to even describe the composition of NORS and that there is no reasonable expectation of success.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). In this case, as mentioned previously, Tawashi teaches that nitric oxide can be applied and used clinically in the treatment of a variety of diseases and teaches the composition in the form of an inhaler which is delivered to the lungs. Sanotize discloses that nitric oxide releasing solution inactivated more than 99.9% of SARS-COV-2, the virus that causes COVID-19. Therefore, one skilled in the art would have been highly motivated to utilize the nitric oxide releasing composition of Tawashi to treat SARS-COV-2 or COVID-19 with a reasonable expectation of success. Thus, applicant’s argument that Sanotize fails to even describe the composition of NORS is not persuasive.
Regarding Mirazimi, applicant argued Mirazimi fails to remedy the deficiencies of Tawashi and Sanotize. In response, as discussed supra, applicant’s arguments regarding Tawashi ans Sanotize are not found persuasive and thus, argument regarding Mirazimi failing to remedy the deficiencies is also not found persuasive.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/A.S/Examiner, Art Unit 1616
/ERIN E HIRT/Primary Examiner, Art Unit 1617