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 .
Priority
The instant application was filed 03 October 2022 and is the national stage entry of PCT/US/21/25915 filed 06 April 2021. The Applicant claims priority to provisional application 63/005,846 filed 06 April 2020. The earliest priority for the remdesivir limitation can be found from PCT/US/21/25915. Therefore, instant claims 4 and 29 receive an effective filing date of 06 April 2021 and the rest of the claims have an effective filing date of 06 April 2020.
Examiner’s Note
The Applicant's amendments and arguments filed 16 January 2026 are acknowledged and have been fully considered. The Examiner has re-weighed all the evidence of record. Rejections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application. In the Applicant’s response, filed 16 January 2026, it is noted that claim 32 has been amended and no claims have been newly added or canceled. Support for the amendments can be found in Figures 1-4 in the instant specification references for reduction in nucleocapsid viral protein and viral titer, but it is unclear where support for replication-competent virions can be found.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claim 32 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The Applicant’s amendment recites “a reduction in the number of replication-competent virions, a reduction in nucleocapsid viral protein, a reduction in the viral titer.” It is unclear where support for the new limitations, such as replication-competent virions, may be found. The Applicant is asked to clarify where support for this new limitation may be found.
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.
Claim(s) 1, 2, 4, 5, 10, 12, 14, 17-19, 32-40 is/are rejected under 35 U.S.C. 103 as being unpatentable over Wu et al. (US 9365506 B2), Glick (US 10980756 B1), and Davis et al. (Safety of an Alkalinizing Buffer Designed for Inhaled Medications in Humans, Respiratory Care, 2012), as evidenced by news-medical.net, biocompare.com, and lenntech.com.
Wu et al. teach compositions and methods for treating SARS coronavirus (col. 45, ln. 11), where the broadness of SARS coronavirus is interpreted as addressing SARS-CoV-2 in claim 40. The composition may be in the form of an aerosol (col. 49, ln. 62) and may be administered in multiple doses (col. 90, ln. 17). The formulation may comprise pH buffering agents (col. 91, ln. 65), antiviral agents (col. 53, ln. 31), and serine inhibitors (col. 59, ln. 6), addressing claim 19. The composition comprising antiviral agents and delivered in multiple doses is interpreted as addressing the limitation of delivering an antiviral in a second composition in claims 1 and 33. The composition comprising antiviral agents is interpreted as reducing viral replication and therefore viral titer; the composition comprising serine inhibitors is interpreted as inhibiting the cathepsin pathway (news-medical.net, pg. 1), addressing claims 2 and 32. Wu teaches that active compounds may be treated with a suitable base, such as sodium hydroxide (col. 27, ln. 42), and an acceptable base addition salt for the compound may be glycine (col. 27, ln. 34), which is interpreted as the buffer and a titrating base, addressing claims 5 and 37. Sodium hydroxide has a pH of 14 (lenntech.com, pg. 1), addressing claim 10, and a glycine buffer system may have a pH range of around 8 (biocompare.com, pg. 3), addressing claim 36.
Certain embodiments may comprise sodium chloride injection (col. 48, ln. 42), which is interpreted as an osmotic balancing agent to replenish lost water and salt. Since the composition may be administered in an aqueous solution (col. 49, lns. 62-65) and may be inhaled through nasal administration (col. 8, ln. 16), the composition is interpreted as an aqueous solution safe for inhalation with a nebulizer device (col. 50, ln. 22), addressing claims 12 and 14. Wu teaches that the therapeutic amount can vary based on different factors (col. 46, lns. 16-20), where it is interpreted that the various amounts of active agents will also change the amounts of other components. The method thus far addressing the limitations of a glycine buffer, sodium hydroxide, and sodium chloride to reduce infection in a subject in claim 32. Wu also describes variability in delivery methods through inhalation, where the device may use several containers or cartridges to deliver different components (col. 49, ln. 59-col. 50, ln. 29). The variability in delivery and administration tactics is interpreted as addressing the antiviral or serine protease inhibitor delivered before or after the buffer in claims 34 and 35.
Wu does not specifically teach a pH range, remdesivir, specific concentrations, or delivery amounts. Wu does not specifically teach that the pH of cells raises to between 8.0-10.5 in claim 39.
Glick teaches compositions and methods for treating COVID-19 (abs). The composition may be in the form of an intranasal aerosol (col. 64, lns. 37-40) and may comprise a buffer system, sodium chloride as a filler (col. 74, lns. 15-23), glycine as a buffer (col. 59, lns. 38-39), cathepsin inhibitors (col. 43, ln. 31), serine inhibitors (col. 29, ln. 39), and remdesivir as a second therapeutic agent (col. 9, lns. 51-55). The formulation may be administered in one or more doses (col. 22, lns. 10-12). Examples of buffers include glycine (col. 59, lns. 38-39), a phosphate buffer system, bicarbonate buffer system, or bisulfate buffer system (col. 73, lns. 57-61). The formulation comprising serine inhibitors and an antiviral, such as remdesivir, is interpreted as inhibiting the cathepsin pathway and reducing viral replication (news-medical.net, pg. 1). The delivery dose may be about 2.5 mg/mL or 7.5 mg/mL (col. 82, lns. 2-3). Glick also teaches a method of monitoring a subject by measuring the reduction in virus (col. 20, ln. 58-col. 22, ln. 14), which is interpreted as a reduction in viral titer in claim 32.
Davis et al. teach inhaled glycine buffer generally increases the pH of the airway (abs).
In regards to selecting the combination of a buffer system comprising glycine, sodium chloride, and sodium hydroxide, “[w]hen a patent simply arranges old elements with each performing the same function it had been known to perform and yields no more than one would expect from such an arrangement, the combination is obvious.” KSR v. Teleflex, 127 S.Ct. 1727, 1740 (2007) (quoting Sakraida v. A.G.Pro, 425 U.S. 273, 282 (1976)). “When the question is whether a patent claiming the combination of elements of prior art is obvious,” the relevant question is “whether the improvement is more than the predictable use of prior art elements according to their established functions.” (Id.). Addressing the issue of obviousness, the Supreme Court noted that the analysis under 35 USC 103 “need not seek out precise teachings directed to the specific subject matter of the challenged claim, for a court can take account of the inferences and creative steps that a person of ordinary skill in the art would employ.” KSR at 1741. The Court emphasized that “[a] person of ordinary skill is… a person of ordinary creativity, not an automaton.” Id. at 1742.
Consistent with this reasoning, it would have been obvious to have selected various
combination of various disclosed ingredients from within a prior art disclosure, to arrive at compositions “yielding no more than one would expect from such an arrangement.”
Wu teaches compositions and methods for making an intranasal aerosol formulation comprising glycine, sodium hydroxide, and sodium chloride, whereas the claimed invention is directed towards methods and compositions comprising contacting the airways with a solution comprising a buffer, titrating base, and an osmotic balancing agent. Since Wu teaches the individual components of the claimed composition, it is obvious for one of ordinary skill in the art to select the different combinations of ingredients to arrive at the claimed invention with a reasonable expectation of success.
Since Wu does not specifically teach a pH range or remdesivir, one of ordinary skill in the art would have been motivated to use the teachings from Glick and staff.ustc to address the deficiencies. Wu teaches using antivirals in their inhalable aerosol composition and Glick teaches remdesivir as an antiviral in their inhalable aerosol composition in claim 4. Wu does not teach a specific pH range but uses buffering agents comprising glycine and staff.ustc teaches a pH range for glycine buffer systems in claim 1. One of ordinary skill in the art would have been motivated to combine the teachings with a reasonable expectation of success, as Glick and Wu provide teachings for antiviral inhalable compositions for treating coronavirus.
Since Wu does not specifically teach that the pH of cells raises to between 8.0-10.5 in claim 39, one of ordinary skill in the art would have been motivated to use Davis’ teaching that inhaled glycine buffer generally increases the pH of the airway to address this deficiency. Since Wu teaches an inhalable composition that may comprise a glycine buffer, it is obvious based on Davis’ teaching that the pH of the cells would also necessarily increase. Assuming the cells are about at physiological pH, a skilled artisan would recognize that the amount the pH rises would also depend on other factors, such as concentration.
Wu teaches that the therapeutic amount can vary based on different factors, where it is interpreted that the various amounts of active agents will also change the amounts of other components (col. 46, lns. 16-20), such as the buffer, titrating base, and osmotic balancing agent, in claims 1, 18, 38. Glick teaches that the delivery dose may be about 2.5 mg/mL or 7.5 mg/mL (col. 82, lns. 2-3) in claim 17. Davis also teaches various concentrations, such as 17.8 mmol/L of glycine buffer, sodium chloride, and sodium hydroxide mixture (pg. 1228, left column para. 1 and right column para. 3). That being said and in lieu of objective evidence of unexpected results, the concentrations and amounts can be viewed as a variable that achieves the recognized result of successfully making the inhalable aerosol composition. The optimum or workable range of concentrations and amounts can be accordingly characterized as routine optimization and experimentation (see MPEP 2144.05 (II)B). “[Discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art.” In re Boesch, 617 F.2d 272, 276 (CCPA 1980). Applicants provide no evidence of any secondary consideration such as unexpected results that would render the optimized amounts of glycine, sodium chloride, and sodium hydroxide as nonobvious.
Claim(s) 1, 2, 4, 5, 10, 12, 14, 15, 17-19, 32-40 is/are rejected under 35 U.S.C. 103 as being unpatentable over Wu et al. (US 9365506 B2), Glick (US 10980756 B1), Davis et al. (Safety of an Alkalinizing Buffer Designed for Inhaled Medications in Humans, Respiratory Care, 2012), and allcarepharmacy.com, as evidenced by news-medical.net, biocompare.com, and lenntech.com.
In regards to claim(s) 1, 2, 4, 5, 10, 12, 14, 17-19, 32-40, Wu, Glick, and Davis, as applied supra, is herein applied in its entirety for its teachings of an inhalable aerosol composition comprising glycine, sodium hydroxide, and sodium chloride.
Wu does not specifically teach a temperature range for the solution in claim 15.
Allcarepharmacy.com generally teaches a large temperature range for storage of inhalable medications, such as 20-25°C (pgs. 1-4), where it is interpreted that the storage temperature is similar to the temperature prior to administration.
Since Wu does not teach a specific temperature range in claim 15, one of ordinary skill in the art would have been motivated to use the temperature range from allcarepharmacy.com to address the deficiencies, as Wu teaches an inhalable medication and allcarepharmacy.com teaches a large range of storage temperatures for different inhalable medications.
Response to Arguments
Applicant's arguments filed 16 January 2026 have been fully considered but they are not persuasive.
The Applicant argues that Wu teaches glycine as a base addition salt and not as a buffer (Remarks, pgs. 7-8).
Applicant’s argument is not found persuasive. Wu teaches buffering agents as well as glycine as a base addition salt. Although it is interpreted that some base addition salts are capable of forming buffer solutions, Glick additionally teaches glycine as a suitable buffer in their intranasal aerosol composition and method for treating COVID-19 (col. 59, lns. 38-39). One of ordinary skill in the art would have been motivated to combine the teachings with a reasonable expectation of success, as Glick and Wu provide teachings for antiviral inhalable compositions for treating coronavirus.
The Applicant argues that the art does not teach the importance of the concentration of the buffer (Remarks, pgs. 9-10).
Applicant’s argument is not found persuasive. Wu teaches diluents, such as glycine, are used to stabilize compounds (col. 14, lns. 37-40). Glick teaches sodium chloride injections may be used as coformers, which are described as reducing the particle size of compounds and improving bioavailability (col. 36, ln. 62-col. 37, ln. 23; col. 6, lns. 27-31). Furthermore, Wu teaches that the therapeutic amount can vary based on different factors, where it is interpreted that the various amounts of active agents will also change the amounts of other components (col. 46, lns. 16-20), such as the buffer, titrating base, and osmotic balancing agent, in claims 1, 18, 38. Glick teaches that the delivery dose may be about 2.5 mg/mL or 7.5 mg/mL (col. 82, lns. 2-3) in claim 17. Davis also teaches various concentrations, such as 17.8 mmol/L of glycine buffer, sodium chloride, and sodium hydroxide mixture (pg. 1228, left column para. 1 and right column para. 3). That being said and in lieu of objective evidence of unexpected results, the concentrations and amounts can be viewed as a variable that achieves the recognized result of successfully making the inhalable aerosol composition. The optimum or workable range of concentrations and amounts can be accordingly characterized as routine optimization and experimentation (see MPEP 2144.05 (II)B).
The Applicant argues Example 1 shows unexpected results regarding the reduction of viral replication when the intracellular pH is raised (Remarks, pg. 9).
Applicant’s argument is not found persuasive. Applicant refers to the Examples and Figures to demonstrate that there is a reduction in viral infection and an antiviral effect for SARS-CoV-2 when the intracellular pH is raised. The composition and method taught by the art is for an intranasal composition to treat coronavirus using an alkaline-based buffer system. Coronavirus is known in the art as a pH-dependent virus (Jung, pg. 2) and SARS-CoV-2 is known in the art to require an acidic pH to infect cells (Kreutzberger title, abs). Therefore, it is not unexpected or surprising that a pharmaceutical formulation with an alkaline pH would reduce viral replication and infection.
Additionally, the adjustment of particular conventional working conditions (e.g., determining result effective amounts of the ingredients beneficially taught by the cited references, especially within the broad ranges instantly claimed), is deemed merely a matter of judicious selection and routine optimization which is well within the purview of the skilled artisan. “[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). Accordingly, this type of modification would have been well within the purview of the skilled artisan and no more than an effort to optimize results. Therefore, it would be obvious to, for example, adjust the pH to maintain a stable composition for the intended purpose, e.g. for creation of a stable intranasal composition to treat coronavirus.
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 Danielle Kim whose telephone number is (571)272-2035. The examiner can normally be reached M-F: 9-5 p.m. PST.
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/D.A.K./Examiner, Art Unit 1613
/ANDREW S ROSENTHAL/Primary Examiner, Art Unit 1613