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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 17 June 2026 has been entered.
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 17 June 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 Rejections not reiterated from previous office actions are hereby withdrawn.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 are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application. In the Applicant’s response, filed 17 June 2026, it is noted that claims 1, 10, 19, 32, 37-39 have been amended, claims 2 and 12 have been canceled, and claim 41 has been newly added. Support for the amendments can be found in at least para. 128 of the instant specification. No new matter has been added.
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.
Claim 41 is 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.
Claim 41 recites “camostat methylate,” however, the art teaches “camostat mesylate.” The metes and bounds of the limitation cannot be determined because the name of the compound is not clear. The claim is herein examined and interpreted as “camostat mesylate,” as consistent with the art.
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, 4, 5, 10, 14, 17-19, 32-41 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, lenntech.com, and drugs.com.
Regarding claim 1, Wu et al. teach compositions and methods for treating SARS coronavirus (col. 45, ln. 11). The composition may be in the form of an aerosol (col. 49, ln. 62), which is interpreted as addressing “contacting the airways of a subject.” The formulation may comprise pH buffering agents (col. 91, ln. 65), antiviral agents (col. 53, ln. 31), and serine inhibitors (col. 59, ln. 6). The composition may be administered in multiple doses (col. 90, ln. 17). The composition comprising antiviral agents and delivered in multiple doses is interpreted as addressing the limitation of delivering an antiviral or serine inhibitor in a second composition. Wu teaches that active compounds may be treated with a suitable base, such as sodium hydroxide (col. 27, ln. 42), and a diluent (col. 47, lns. 56-57) or 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. Glycine buffer systems may have a pH range of around 8 (biocompare.com, pg. 3), which is interpreted as addressing “about 8 to about 11.5.” 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), which is interpreted as addressing the limitation of “inhibits the CatL/B pathway.” It is noted that the solution in step a) uses “comprising” language. Therefore, the solution in step a) allows the inclusion of antiviral agents and serine inhibitors.
Regarding claim 5, the solution may comprise an acceptable base addition salt, such as glycine (col. 27, ln. 34) for the active compounds.
Regarding claim 10, sodium hydroxide has a pH of 14 (lenntech.com, pg. 1), which is interpreted as addressing “about 11.5.”
Regarding claim 14, 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).
Regarding claim 19, the composition comprising antiviral agents or serine inhibitors (col. 59, ln. 6) and delivered in multiple doses (col. 90, ln. 17) is interpreted as addressing the limitation of delivering an antiviral or serine inhibitor in a second composition.
Regarding claim 32, Wu et al. teach compositions and methods for treating SARS coronavirus (col. 45, ln. 11). The composition may be in the form of an aerosol (col. 49, ln. 62), which is interpreted as addressing “contacting the airways of a subject.” The formulation may comprise pH buffering agents (col. 91, ln. 65), antiviral agents (col. 53, ln. 31), serine inhibitors (col. 59, ln. 6), and osmotic balancing agent, such as sodium chloride injection (col. 48, ln. 42) to replenish lost water and salt. 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. The composition comprising antiviral agents is interpreted as reducing viral replication and therefore viral titer and infection.
Regarding claim 33, the formulation may comprise pH buffering agents (col. 91, ln. 65), antiviral agents (col. 53, ln. 31), and serine inhibitors (col. 59, ln. 6). The composition may be administered in multiple doses (col. 90, ln. 17). The composition comprising antiviral agents and delivered in multiple doses is interpreted as addressing the limitation of delivering an antiviral or serine inhibitor in a second composition.
Regarding claim 34, the composition may be administered in multiple doses (col. 90, ln. 17). The composition comprising antiviral agents and delivered in multiple doses is interpreted as addressing the limitation of delivering an antiviral or serine inhibitor in a second composition or after the first composition comprising the buffer. 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.
Regarding claim 35, as mentioned above, Wu 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.
Regarding claim 36, glycine buffer systems may have a pH range of around 8 (biocompare.com, pg. 3), which is interpreted as addressing “about 9.4 to about 9.8.”
Regarding claim 37, the solution may comprise an acceptable base addition salt, such as glycine (col. 27, ln. 34) for the active compounds.
Regarding claim 40, Wu et al. teach compositions and methods for treating SARS coronavirus (col. 45, ln. 11), where the broadness of SARS coronavirus is interpreted as SARS-CoV-2.
Wu does not specifically teach remdesivir, specific concentrations, or delivery amounts in claims 1, 4, 17, 18, and 38. Wu does not specifically teach that the pH of cells are raised to between 8.0-10.5 in claim 39. Wu does not specifically teach camostat mesylate in claim 41.
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, such as camostat (col. 30, ln. 12; interpreted as camostat mesylate (evidenced by drugs.com, pg. 2)), 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.
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 remdesivir in claim 4 or camostat mesylate in new claim 41, one of ordinary skill in the art would have been motivated to use the teachings from Glick to address the deficiencies. Wu teaches using antivirals in their inhalable aerosol composition and serine inhibitors, and Glick teaches remdesivir as an antiviral in their inhalable aerosol composition and camostat mesylate as serine inhibitors. “Generally, it is prima facie obvious to select a known material for incorporation into a composition, based on its recognized suitability for its intended use (see MPEP § 2144.07).”
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. “Generally, it is prima facie obvious to select a known material for incorporation into a composition, based on its recognized suitability for its intended use (see MPEP § 2144.07).”
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, 17, 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 regards to 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 15 is rejected under 35 U.S.C. 103 as being unpatentable over Allcarepharmacy.com, as applied to claims 1, 4, 5, 10, 14, 17-19, 32-41 above, in view of 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, lenntech.com, and drugs.com.
In regards to claim(s) 1, 4, 5, 10, 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. “Generally, it is prima facie obvious to select a known material for incorporation into a composition, based on its recognized suitability for its intended use (see MPEP § 2144.07).”
Response to Arguments
Applicant's arguments filed 17 June 2026 have been fully considered but they are not persuasive.
The Applicant argues that amended claims 1 and 32 recite that the solution administered in step a) inhibits the CatL/B pathway and reduces the viral infection rate. The Applicant further argues unexpected results that allegedly show that the alkalinized buffer comprising glycine resulted in decreasing viral replication without the addition of an antiviral or protease inhibitor (Remarks, pgs. 7-8).
Applicant’s argument is not found persuasive. Hevia (US 2006/0052454) speculates that glycine helps to strengthen and reinforce connective tissue, which impedes the advance of invasive agents, such as viruses. Therefore, it is interpreted that glycine contributes an antiviral effect to compositions and a reduction in viral titer or replication rate would inherently occur. It is noted that “products of identical chemical composition cannot have mutually exclusive properties.” A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990) (see MPEP 2112.01 (II)).
The Applicant argues that Wu uses glycine as a diluent or base addition salt and not as a buffer (Remarks, pgs. 8-9).
Applicant’s argument is not found persuasive. Wu’s use of glycine as a diluent is interpreted as being similar to a buffer (Makela, US 5,185,264, col. 1, lns. 6-8). Wu adding glycine as a solution, even as intended as a diluent, is therefore expected to have a similar effect to a buffering system. A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990) (see MPEP 2112.01 (II)).
The Applicant argues that Wu teaches away from using glycine as a buffer (Remarks, pgs. 9-10).
Applicant’s argument is not found persuasive. In response to the Applicant's argument that the references fail to show certain features of applicant’s invention, it is reminded that to properly teach away, the prior art reference must criticize, discredit, or otherwise discourage the solution sought. Merely teaching alternatives does not do this (see MPEP 2145 (X)(D)).
The Applicant argues unexpected results regarding the reduction of viral replication rate allegedly demonstrated in Fig. 1 and Examples 4 and 5 (Remarks, pgs. 9-10).
Applicant’s argument is not found persuasive. Hevia (US 2006/0052454) speculates that glycine helps to strengthen and reinforce connective tissue, which impedes the advance of invasive agents, such as viruses. Therefore, it is interpreted that glycine contributes an antiviral effect to compositions and a reduction in viral titer or replication rate would inherently occur. It is noted that “products of identical chemical composition cannot have mutually exclusive properties.” A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990) (see MPEP 2112.01 (II)).
Furthermore, in regards to the concentrations of the various elements, 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, 17, 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 regards to 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). Therefore, 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.
Conclusion
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/D.A.K./Examiner, Art Unit 1613
/ANDREW S ROSENTHAL/Primary Examiner, Art Unit 1613
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