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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 03/12/2026 has been entered.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 03/12/2026 has been considered by the examiner.
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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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 1, 3-4, 7, 9-11, 13, 15, 19, 25-26, 31-32, 37-38, and 76 are rejected under 35 U.S.C. 103 as being unpatentable over Gnopeck et al. WO 2006/101882 further in view of Brambilla et al. 2014/0060531.
Regarding claim 1, Gnopeck discloses a pressurized oral (“a chamber in fluid communication with a patient port for introducing the medicament into the oral and/or nasal cavity of the patient, preferably in the form of a mouthpiece”) metered dose inhaler (“Certain aspects of the present invention thus provide inhalers, and preferably metered dose inhalers (MDIs) for the treatment of asthma and other chronic obstructive pulmonary diseases and for delivery of medicaments to accessible mucous membranes or intranasally.“) comprising: a canister containing a formulation (aerosol container 2) comprising an active pharmaceutical ingredient (API) selected from the group consisting of epinephrine, a pharmaceutically acceptable salt of epinephrine, and a vaccine (Page 10 lists epinephrine as one of the potential active agents. Claim 5 states the potential for a vaccine being the active compound.); and an actuator having one or more orifices (“The actuator also preferably includes a nozzle block adapted to receive the valve stem of the dispensing valve, the nozzle block preferably comprising a passage in fluid communication with the valve stem and terminating in an orifice for directing medicament from the valve stem into the chamber.”), wherein the API is in suspension (Claim 3 states “in the form of a medicinal preparation for propellant driven application wherein said at least one medicinally active compound is in the form of a suspension or a solution with said propellant.”).
Gnopeck fails to explicitly teach the orifice having an effective diameter of from about 0.16 mm to about 0.29 mm. Brambilla discloses an analogous oral inhaler (0003) that does teach an orifice (orifice 8, figure 2) with an effective diameter of from about 0.16 mm to about 0.29 mm (0111 states “Actuator (exit) orifices having a diameter in the range 0.15 to 0.45 mm and a length from 0.30 to 1.7 mm are generally suitable. Preferably, an orifice having a diameter from 0.2 to 0.44 mm is used, e.g. 0.22, 0.25, 0.30, 0.33, or 0.42 mm. In certain embodiments, it may be useful to utilize actuator orifices having a diameter ranging from 0.10 to 0.22 mm, in particular from 0.12 to 0.18 mm.”) It would have been prima facie obvious for one of ordinary skill in the art to modify Gnopeck with the teachings of Brambilla and include the orifices having an effective diameter of from about 0.12 mm to about 0.33 mm as this would increase the duration of the aerosol cloud generation and coordinate the cloud generation with the slow inspiration of the patient (0112).
Regarding claim 3, Gnopeck further discloses the pressurized oral metered dose inhaler of claim 1 wherein the API is epinephrine or a pharmaceutically acceptable salt thereof (Page 10 of Gnopeck lists epinephrine as one of the potential active agents
Regarding claim 4, modified Gnopeck discloses the pressurized oral metered dose inhaler of claim 3, the effective diameter of the one or more orifices is from about 0.18 mm to about 0.27 mm (0111 of Brambilla states “Actuator (exit) orifices having a diameter in the range 0.15 to 0.45 mm”).
Regarding claim 7, modified Gnopeck further discloses the pressurized oral metered dose inhaler of claim 4 wherein the effective diameter of the one or more orifices is from about 0.20 mm to about 0.25 mm (0111 of Brambilla states “Actuator (exit) orifices having a diameter in the range 0.15 to 0.45 mm”).
Regarding claim 9, modified Gnopeck further discloses the pressurized oral metered dose inhaler of claim 7 the effective diameter of the one or more orifices is about 0.22 mm (0111 of Brambilla states “Actuator (exit) orifices having a diameter in the range 0.15 to 0.45 mm”).
Regarding claim 10, modified Gnopeck further discloses the pressurized oral metered dose inhaler of claim 9 wherein the effective diameter of the one or more orifices is 0.22 mm (0111 of Brambilla states “Actuator (exit) orifices having a diameter in the range 0.15 to 0.45 mm”).
Regarding claim 11, modified Gnopeck further discloses the pressurized oral metered dose inhaler of any one of claim 3 wherein the one or more orifices are circular (Figure 3c of Brambilla depicts the discharge orifice 8 as circular).
Regarding claim 13, modified Gnopeck further discloses the pressurized oral metered dose inhaler of claim 11 wherein the actuator has a single orifice ( Figure 3c of Brambilla depicts a singular discharge orifice.).
Regarding claim 15, Gnopeck further discloses the pressurized oral metered dose inhaler of claim 3 wherein the formulation further comprises:
a liquefied propellant (Page 11 of Gnopeck discusses the use of a propellant ) ;
and a co-solvent (Page 17 of Gnopeck discusses the use of a co-solvent)
Regarding claim 19, Gnopeck further discloses the pressurized oral metered dose inhaler of claim 15 wherein the co-solvent is at least one of ethanol, isopropanol, propylene glycol, ethylene glycol, propane, butane, isobutene, pentane, dimethyl ether, diethyl ether, or a mixture thereof (Page 17 of Gnopeck lists propylene glycol, as one of the potential co-solvents).
Regarding claim 25, Gnopeck further discloses the pressurized oral metered dose inhaler of claim 15 wherein the liquefied propellant is at least one of 1,1,1,2-tetrafluoroethane (HFA-134A), 1,1,1,2,3,3,3- heptafluoropropane (HFA-227), or a mixture thereof (Page 16 of Gnopeck states the use of “1 ,1 ,1 ,2- tetrafluoroethane (HFC-134a)); and hydrofluorpropanes (eg., 1 ,1 ,1 ,2,3,3,3- heptafluoropropane (HFC-227ea)).”).
Regarding claim 26, Gnopeck further discloses the pressurized oral metered dose inhaler of claim 25 wherein the liquefied propellant is 1,1,1,2- tetrafluoroethane (HFA-134A). (Page 16 of Gnopeck states the use of “1 ,1 ,1 ,2- tetrafluoroethane (HFC-134a)); and hydrofluorpropanes (eg., 1 ,1 ,1 ,2,3,3,3- heptafluoropropane (HFC-227ea)).”)
Regarding claim 31, Gnopeck further discloses the pressurized oral metered dose inhaler of claim 15 wherein the formulation further comprises a surfactant (Paragraph 17 states that “In addition, the present compositions may include one or more other special purpose adjuvants, such as a cosolvent(s) and/or surfactant(s) that enhance the composition”).
Regarding claim 32, Gnopeck further discloses the pressurized oral metered dose inhaler of claim 31 wherein the surfactant is selected from mono- or poly-sorbitan oleates, oleic acid, and lecithin (Paragraph 19 states that “More specific examples of acceptable surface active agents include oleic acid, sorbitan mono-, di- or trioleate, and combinations of two or more thereof.”).
Regarding claim 37, Gnopeck further discloses the pressurized oral metered dose inhaler of claim 1 wherein the API is a vaccine (Claim 5 of Gnopeck states the potential for a vaccine being the active compound).
Regarding claim 38, Gnopeck teaches a method of treating a patient in need (page 24 states “Certain aspects of the present invention thus provide inhalers, and preferably metered dose inhalers (MDIs) for the treatment of asthma and other chronic obstructive pulmonary diseases and for delivery of medicaments to accessible mucous membranes or intranasally.”) of epinephrine or a pharmaceutically acceptable salt thereof (page 10 states that one of the active compounds is epinephrine), comprising delivering one or more oral inhaled doses of the epinephrine or a pharmaceutically acceptable salt thereof to the patient by means of the pressurized oral metered dose inhaler of claim 3 (taught by Gnopeck).
Regarding claim 76, Gnopeck discloses a kit for making a pressurized oral metered dose inhaler (page 24 states “Certain aspects of the present invention thus provide inhalers, and preferably metered dose inhalers (MDIs) for the treatment of asthma and other chronic obstructive pulmonary diseases and for delivery of medicaments to accessible mucous membranes or intranasally.“), the kit comprising: a canister (aerosol container 2) containing a formulation comprising epinephrine or a pharmaceutically acceptable salt thereof (Page 10 lists epinephrine as one of the potential active agents) wherein the epinephrine or a pharmaceutically acceptable salt thereof is in suspension (Claim 3 states “in the form of a medicinal preparation for propellant driven application wherein said at least one medicinally active compound is in the form of a suspension or a solution with said propellant.”); and an actuator adapted to house the canister, the actuator having one or more orifices (Page 21 states “The actuator also preferably includes a nozzle block adapted to receive the valve stem of the dispensing valve, the nozzle block preferably comprising a passage in fluid communication with the valve stem and terminating in an orifice for directing medicament from the valve stem into the chamber.”).
Gnopeck does not explicitly disclose an effective diameter of from about 0.16 mm to about 0.29 mm, however Brambilla discloses an analogous inhaler that does teach an orifice with an effective diameter of from about 0.16 mm to about 0.29 mm (0111 states “Actuator (exit) orifices having a diameter in the range 0.15 to 0.45 mm and a length from 0.30 to 1.7 mm are generally suitable. Preferably, an orifice having a diameter from 0.2 to 0.44 mm is used, e.g. 0.22, 0.25, 0.30, 0.33, or 0.42 mm. In certain embodiments, it may be useful to utilize actuator orifices having a diameter ranging from 0.10 to 0.22 mm, in particular from 0.12 to 0.18 mm.”) It would have been prima facie obvious for one of ordinary skill in the art to modify Gnopeck with the teachings of Brambilla and include the orifices having an effective diameter of from about 0.12 mm to about 0.33 mm as this would increase the duration of the aerosol cloud generation and coordinate the cloud generation with the slow inspiration of the patient (0112).
Claim 77 is rejected under 35 U.S.C. 103 as being unpatentable over modified Gnopeck.
Regarding claim 77, modified Gnopeck teaches the pressurized oral metered dose inhaler of claim 3 with the delivery of a metered dose (Pages 20-24 of Gnopeck), but is silent to the inhaler having up to 50 inhalation doses. It would have been obvious for one of ordinary skill in the art to configure Gnopeck to deliver up to 50 inhalation doses to provide optimal treatment for the patient.
Claim 14 is rejected under 35 U.S.C. 103 as being unpatentable over Gnopeck and Brambilla, further in view of Robertson et al. 5,515,841.
Regarding claim 14, modified Gnopeck discloses the pressurized oral metered dose inhaler of claim 11, but fails to teach wherein the actuator has a plurality of orifices. Robertson discloses an analogous inhaler that does disclose wherein the actuator has a plurality of orifices (The abstract states “a nozzle arrangement comprising a plurality of orifices,”). It would have been prima facie obvious for one of ordinary skill in the art to modify modified Gnopeck with Robertson to include wherein the actuator has a plurality of orifices as doing so provides the patient with an evenly distributed inhalation of medication wherein the liquid is expelled through the outer surface of the nozzle by way of atomized droplets (abstract).
Claims 16 is rejected under 35 U.S.C. 103 as being unpatentable over Gnopeck and Brambilla, further in view of Vega et al. 2012/0207685.
Regarding claim 16, modified Gnopeck discloses the pressurized oral metered dose inhaler of claim 15, but fails to teach wherein the co-solvent is present from about 0.1% to about 4% w/w based on the total weight of the formulation. Vega discloses an analogous metered dose inhaler containing a medicinal aerosol which in combination with Gnopeck further discloses wherein the co-solvent is present from about 0.1% to about 4% w/w based on the total weight of the formulation. In paragraph 0016, Vega states that the amount of alcohol to be used should be between 0.1% to 20% w/w. One of ordinary skill in the art would have the ability to simply adjust the weight percent of the co-solvent to contain the overlapping ranges disclosed in both references as doing so allows for the experimentation of the effect that varying the amount of co-solvent has on the solubilization of the active ingredient (0013).
Claims 21 and 23 are rejected under 35 U.S.C. 103 as being unpatentable over Gnopeck and Brambilla, further in view of Eck et al. 9,717,683.
Regarding claim 21, modified Gnopeck discloses the pressurized oral metered dose of claim 15, but fails to teach wherein the liquefied propellant is present from about 95% to about 99.5% w/w based on the total weight of the formulation. Eck discloses an analogous inhalation composition that does teach wherein the liquefied propellant is present from about 95% to about 99.5% w/w based on the total weight of the formulation. Column 8 line 2 of Eck discloses that the composition of propellent can typically range from 50%-99.5% w/w. One of ordinary skill in the art would have the ability to simply adjust the weight percent of the liquified propellent to contain the overlapping ranges disclosed in both references as doing so allows for the experimentation of the effect of the liquified propellant weight percent on the atomization of the active ingredient.
Regarding claim 23 modified Gnopeck in view of Eck discloses the pressurized oral metered dose inhaler of claim 21, wherein the liquefied propellant is present from about 97% to about 99% w/w based on the total weight of the formulation (Column 8 line 2 of Eck discloses that the composition of propellent can typically range from 50%-99.5% w/w.).
Claims 27, 29-30 and 33-34 are rejected under 35 U.S.C. 103 as being unpatentable over Gnopeck and Brambilla, further in view of Gao et al. 8,367,734
Regarding claim 27, modified Gnopeck discloses the pressurized oral metered dose inhaler of claim 3, but fails to teach wherein the API is present from about 0.1% to about 0.5% w/w based on the total weight of the formulation. Gao discloses an analogous formulation that does disclose wherein the API is present from about 0.1% to about 0.5% w/w based on the total weight of the formulation (Column 4 line 64). It would have been prima facie obvious to one of ordinary skill in the art to include wherein the API is present from about 0.1% to about 0.5% w/w based on the total weight of the formulation as this range allows for the experimentation on the effects of w/w% epinephrine used, against the stimulation of alpha- and beta-adrenergic receptors (0003).
Regarding claim 29, modified Gnopeck in view of Gao discloses the pressurized oral metered dose inhaler of claim 27. Gao further discloses wherein the API is present from about 0.1% to about 0.3% w/w based on the total weight of the formulation (Column 4 line 64). It would have been prima facie obvious to one of ordinary skill in the art to include wherein the API is present from about 0.1% to about 0.3% w/w based on the total weight of the formulation as this range allows for the experimentation on the effects of w/w% epinephrine used, against the stimulation of alpha- and beta-adrenergic receptors (0003).
Regarding claim 30, modified Gnopeck in view of Gao discloses the pressurized oral metered dose inhaler of claim 29. Gao further discloses wherein the API is epinephrine free base (Column 4 line 58). It would have been prima facie obvious to one of ordinary skill in the art to include wherein the API is wherein the API is epinephrine free base as epinephrine allows for the stimulation of alpha- and beta-adrenergic receptors (0003).
Regarding claim 33, modified Gnopeck discloses the oral pressurized metered dose inhaler of claim 15, but fails to teach wherein the formulation further comprises an antioxidant. Gao does disclose wherein the formulation further comprises an antioxidant (Column 6 line 3 states that “a small amount of antioxidant, preferably less than 0.05% w/w of the total weight of the formulation, is also added to the formulation.”). It would have been prima facie obvious for one of ordinary skill in the art to include wherein the formulation further comprises an antioxidant as doing so prevents oxidation and maintains stability of the medication (Column 6 line 7).
Regarding claim 34, modified Gnopeck in view of Gao discloses the pressurized oral metered dose inhaler of claim 33, wherein the antioxidant is selected from thymol, tocopherol, ascorbyl palmitate, butylated hydroxyanisole, butylated hydroxytoluene, propyl gallate, citric acid, sodium metabisulfite, and sodium sulfite (Column 6 line 11 of Gao states that “The antioxidant that can be used in the present formulation can be selected from the group consisting of thymol, tocopherol, ascorbyl palmitate, butylated hydroxyanisole, butylated hydroxytoluene, propyl gallate, sodium metabisulfite, citric acid, and sodium sulfite.”). It would have been prima facie obvious for one of ordinary skill in the art to include wherein the antioxidant is selected from thymol, tocopherol, ascorbyl palmitate, butylated hydroxyanisole, butylated hydroxytoluene, propyl gallate, citric acid, sodium metabisulfite, and sodium sulfite as doing so prevents oxidation and maintains stability of the medication (Column 6 line 7).
Claim 35 is rejected under 35 U.S.C. 103 as being unpatentable Gnopeck, Brambilla, and Gao further in view of Primatene Mist and Potta et al. 2017/0216199.
Regarding claim 35, modified Gnopeck discloses the pressurized oral metered dose of claim 15. Gnopeck discloses parts of the claimed formulation; however Gao discloses an analogous inhaler formulation that does explicitly disclose wherein: the API is epinephrine free base in suspension (Column 4 line 58);
the liquefied propellant is 1,1,1,2-tetrafluoroethane (HFA-134a), (Column 5, first paragraph);
the co-solvent is ethanol at about 1% w/w based on the total weight of the formulation (Column 7 line 15);
wherein the formulation further comprises polysorbate 80 (Column 7 line 17); and thymol (Column 7 line 18).
Furthermore, the formulation disclosed in Gao is a commonly used formulation found in over the counter aerosol Primatene Mist. The attached drug facts label states that the formulation also contains no sulfites.
Gao does not explicitly disclose the suspension being at a concentration of 1.9% w/w based on the total weight of the formulation, instead disclosing a potential range 0f 0.1-0.5%. However, Potta discloses an analogous epinephrine spray formulation that teaches a range of epinephrine between 0.1% w/w and 15% w/w, indicating that one of ordinary skill in the art can easily adjust the w/w % of epinephrine within a formulation. It would be prima facie obvious for one to do this as the adjustment of the amount of epinephrine allows for the experimentation on the effects of w/w% epinephrine used, against the stimulation of alpha- and beta-adrenergic receptors (0003).
All in all, it would be prima facie obvious for one of ordinary skill in the art to simply replace the formulation of modified Gnopeck with the described modified formulation of Gao and Potta as it is a commonly used and market tested formulation that would provide economic benefit.
Claim 24 is rejected under 35 U.S.C. 103 as being unpatentable Gnopeck and Brambilla further in view of the “Safety Data Sheet”
Regarding claim 24, modified Gnopeck discloses the pressurized oral metered dose of claim 15, but fails to teach wherein the liquefied propellant has a vapor pressure of about 5.5 bar to about 5.9 bar (absolute), at 20-C. However, this is a known value of liquified propellent. Gnopeck discloses the potential propellent as 1,1,1,2-tetrafluoroethane as disclosed on page 16. The given pressure range is a known characteristic possessed by 1,1,1,2-tetrafluoroethane as disclosed on page 4 in the attached safety data sheet for said chemical. The safety data sheet discloses the vapor pressure of the chemical at 5.7 bar at 20 degrees Celsius and one of ordinary skill in the art would have the ability to slightly adjust this vapor pressure at room temperature, in order to optimize the release of the desired drug dose into droplets .
Claim 36 is rejected under 35 U.S.C. 103 as being unpatentable Gnopeck and Brambilla further in view of “Relevance of pharmacokinetics and pharmacodynamics of inhaled corticosteroids to asthma”, “How to use inhalers: Part I – the perfect angle” (https://capmedicinhaler.com/2020/01/12/how-to-use-inhalers-correct-angle/?srsltid=AfmBOopGoc0jHm8armOapXOpUjL7B6wi0q6Sr5UVL2lXw5D0naPsmsJY), and “Guide to Aerosol Delivery Devices”.
Regarding claim 36, modified Gnopeck discloses the pressurized oral metered dose inhaler of claim 15, which is capable of delivering a dose of epinephrine or pharmaceutically acceptable salt (Gnopeck abstract). Neither explicitly discloses such that the proportion of the delivered dose that reaches the larynx, pharynx, and lungs when the metered dose inhaler is in a transverse orientation is at least 90%, of the proportion of the delivered dose that reaches the larynx, pharynx, and lungs when the metered dose inhaler is in an coaxial orientation, as determined with the Sectioned Alberta Idealized Throat at a flowrate of 30 L/min.
“Relevance of pharmacokinetics and pharmacodynamics of inhaled
corticosteroids to asthma” discusses a study that does state the potential of HFA related aerosols to deposit in the lung and pharynx region at a rate of up to 90% (Page 1045 states that “For MF-HFA, lung deposition of 7.4–24.5% and oropharyngeal deposition of 79.1% has been reported”.)
Furthermore, “How to use inhalers: Part I – the perfect angle” discloses the metered dose inhaler in a transverse orientation vs a coaxial orientation. From the disclosed images, it is clear that a coaxial orientation is ideal to maximize medication reaching the lungs, and it is obvious that a more transverse orientation would allow for less medication to reach the intended regions, encompassing the 90% value as opposed to 95%.
Lastly, “Guide to Aerosol Delivery Devices” discloses the flowrate of 30 L/min as being known within the art as the minimum peak inspiratory flow rate to achieve effective drug delivery to the airways (Page 4).
All in all, it would have been prima facie obvious to one of ordinary skill in the art to combine all the listed teachings to include the proportion of the delivered dose that reaches the larynx, pharynx, and lungs when the metered dose inhaler is in a transverse orientation is at least 90%, of the proportion of the delivered dose that reaches the larynx, pharynx, and lungs when the metered dose inhaler is in an coaxial orientation, as determined with the Sectioned Alberta Idealized Throat at a flowrate of 30 L/min as it is a simple case of applying a known technique to a known device as the inclusion of a more coaxial orientation in relation to the proportion of dose that reaches the airway and breathing areas along with a minimum flowrate of 30 L/min is a technique that is necessary to maximize the efficiency of drug delivery.
Claims 20, 39-40, and 78-84 are rejected under 35 U.S.C. 103 as being unpatentable Gnopeck and Brambilla further in view of Batycky et al. 2004/0076588
Regarding claim 20, modified Gnopeck discloses the pressurized oral metered dose inhaler of claim 19, but fails to teach wherein the co-solvent is ethanol. Batycky does teach an analogous inhalable epinephrine wherein the co-solvent is ethanol (Paragraph 00153 states that “Suitable organic solvents that can be employed include but are not limited to alcohols such as, for example, ethanol, methanol, propanol.”). It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify modified Gnopeck with Batycky and include ethanol as a co solvent as it is a common type of cosolvent used for inhalers.
Regarding claim 39, modified Gnopeck teaches the method of claim 38, but fails to explicitly teach wherein the patient is suffering from anaphylaxis. Batycky teaches an analogous inhalable epinephrine that teaches the use of epinephrine when the patient is suffering from anaphylaxis (0012 states “a method for treating a patient in need of rescue therapy for anaphylaxis is contemplated. The method comprises administering particles to the respiratory system of the patient, wherein the particles comprise (a) a therapeutically effective amount of epinephrine, or a salt thereof;”). It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to use the mdi of modified Gnopeck to treat anaphylaxis as it is a common allergic reaction that is treated by epinephrine (0002-0003).
Regarding claim 40, Gnopeck teaches a delivery by oral inhalation (Page 21 states “(“a chamber in fluid communication with a patient port for introducing the medicament into the oral and/or nasal cavity of the patient, preferably in the form of a mouthpiece”) of a therapeutically effective amount of epinephrine or pharmaceutically acceptable salt thereof (Page 10 lists epinephrine as one of the potential active agents) to the patient by means of a pressurized oral metered dose inhaler (page 24 states “Certain aspects of the present invention thus provide inhalers, and preferably metered dose inhalers (MDIs) for the treatment of asthma and other chronic obstructive pulmonary diseases and for delivery of medicaments to accessible mucous membranes or intranasally.“), the pressurized oral metered dose inhaler comprising:
a canister containing a formulation (aerosol container 2) comprising epinephrine or a pharmaceutically acceptable salt thereof (Page 10 lists epinephrine as one of the potential active agents)
and an actuator having one or more orifices (Page 21 states “The actuator also preferably includes a nozzle block adapted to receive the valve stem of the dispensing valve, the nozzle block preferably comprising a passage in fluid communication with the valve stem and terminating in an orifice for directing medicament from the valve stem into the chamber.”), wherein the epinephrine or pharmaceutically acceptable salt thereof is in suspension (Claim 3 states “in the form of a medicinal preparation for propellant driven application wherein said at least one medicinally active compound is in the form of a suspension or a solution with said propellant.”).
Gnopeck does not explicitly disclose an effective diameter of from about 0.16 mm to about 0.29 mm, however Brambilla discloses an analogous inhaler that does teach an orifice with an effective diameter of from about 0.16 mm to about 0.29 mm (0111 states “Actuator (exit) orifices having a diameter in the range 0.15 to 0.45 mm and a length from 0.30 to 1.7 mm are generally suitable. Preferably, an orifice having a diameter from 0.2 to 0.44 mm is used, e.g. 0.22, 0.25, 0.30, 0.33, or 0.42 mm. In certain embodiments, it may be useful to utilize actuator orifices having a diameter ranging from 0.10 to 0.22 mm, in particular from 0.12 to 0.18 mm.”) It would have been prima facie obvious for one of ordinary skill in the art to modify Gnopeck with the teachings of Brambilla and include the orifices having an effective diameter of from about 0.12 mm to about 0.33 mm as this would increase the duration of the aerosol cloud generation and coordinate the cloud generation with the slow inspiration of the patient (0112).
Furthermore, modified Gnopeck does not explicitly disclose this as a method of treating anaphylaxis. Batycky does teach an inhalable epinephrine that teaches the use of epinephrine when the patient is suffering from anaphylaxis (0012 states “a method for treating a patient in need of rescue therapy for anaphylaxis is contemplated. The method comprises administering particles to the respiratory system of the patient, wherein the particles comprise (a) a therapeutically effective amount of epinephrine, or a salt thereof;”). It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to use the mdi of modified Gnopeck to treat anaphylaxis as it is a common allergic reaction that is treated by epinephrine (0002-0003).
Regarding claim 78, modified Gnopeck in view of Batycky teaches the method of claim 39, wherein the method comprises administering two puffs of epinephrine periodically until the patient shows a physiological response to the treatment (0012 of Batycky states “the instant invention comprises a method for treating a patient suffering from anaphylaxis, wherein the method comprises: (a) administering an effective amount of substantially dry particles to the respiratory system of the patient, the particles comprising epinephrine, or a salt thereof; (b) monitoring the patient; and (c) administering additional epinephrine to the patient.” 0037 states “The unique characteristics of aerodynamically light particles comprising epinephrine, or a salt thereof, provide for improved physiological effects such as, for example, increased therapeutic effect(s) or increased duration of therapeutic effect(s).” Batycky is teaching the administration of epinephrine until symptoms improve.).
Regarding claim 79, modified Gnopeck in view of Batycky teaches the method of claim 78, wherein the physiological response is:(a) tachycardia, tremor or both; or (b) the patient's subjective awareness of body or hand tremor or patient's subjective awareness of increased heart rate (0333 of Batycky discusses tremors as a potential adverse event, “Adverse events consistent with alpha and beta-adrenergic agonism (e.g., palpitations, tremor and pallor) appeared to be dose related. The majority of adverse events reflected mechanism-based effects due to alpha and beta-adrenergic stimulation.”)
Regarding claim 80, modified Gnopeck in view of Batycky teaches the method of claim 79, which comprises administering a therapeutically effective amount of epinephrine by administering two puffs once every 1 to 10 minutes until the anaphylactic reaction ameliorates (0189 of Batycky states “the effective amount of the second mass of substantially dry particles are administered at least about 5 minutes after the administration of the effective amount of the first mass of substantially dry particles.”).
Regarding claim 81, modified Gnopeck in view of Batycky teaches the method of claim 78, which comprises administering two puffs once every 2 minutes (0189 of Batycky states “the effective amount(s) of substantially dry particles are administered at least about 0.5, 1, 2, 3, 4, or about 5 minutes after the immediately prior administration of substantially dry particles”).
Regarding claim 82, modified Gnopeck in view of Batycky teaches the method of claim 39, which comprises administering two puffs of epinephrine every 60 seconds until clinical resolution of allergic symptoms is obtained (0189 of Batycky states “the effective amount(s) of substantially dry particles are administered at least about 0.5, 1, 2, 3, 4, or about 5 minutes after the immediately prior administration of substantially dry particles” 0189 states “the effective amount of substantially dry particles is administered while the patient experiences symptoms of anaphylaxis, for example, before the symptoms of anaphylaxis have substantially abated. In one aspect, the effective amount(s) of substantially dry particles are administered during a single episode of anaphylaxis. In another aspect, the effective amount of substantially dry particles is administered while the patient experiences at least one of the conditions selected from the group consisting of bronchoconstriction, bronchospasm, airway constriction, and edema”).
Regarding claim 83, modified Gnopeck in view of Batycky teaches the method of claim 39, which comprises administering two puffs periodically until the patient experiences subjective awareness of a physiological response to treatment (“0189 of Batycky states “the effective amount(s) of substantially dry particles are administered at least about 0.5, 1, 2, 3, 4, or about 5 minutes after the immediately prior administration of substantially dry particles” 0010 states “the invention, a method for treating a patient in need of rescue therapy for anaphylaxis is provided comprising administering particles to the respiratory system of the patient, the particles comprising a therapeutically effective amount of epinephrine, or a salt thereof; wherein the particles are delivered to the respiratory system and the epinephrine reaches its site of action within a time sufficiently short to provide said rescue therapy.”).
Regarding claim 84, modified Gnopeck in view of Batycky teaches the method of claim 83, which comprises administering two pubs every 30-90 seconds until the patient experiences subjective awareness of a physiological response to treatment (“0189 of Batycky states “the effective amount(s) of substantially dry particles are administered at least about 0.5, 1, 2, 3, 4, or about 5 minutes after the immediately prior administration of substantially dry particles” 0010 states “the invention, a method for treating a patient in need of rescue therapy for anaphylaxis is provided comprising administering particles to the respiratory system of the patient, the particles comprising a therapeutically effective amount of epinephrine, or a salt thereof; wherein the particles are delivered to the respiratory system and the epinephrine reaches its site of action within a time sufficiently short to provide said rescue therapy.”).
Response to Arguments
Applicant's arguments filed 03/12/2026 have been fully considered but they are not persuasive. Regarding claims 1, 40, and 76, applicant argues that it would not have been obvious for one of ordinary skill in the art to utilize actuator orifices having an effective diameter of about 0.16 mm to 0.29 mm in a pressurized metered dose inhaler comprising epinephrine in suspension or a vaccine in suspension.
Applicant argues that the prior art teaches that narrow orifice diameters were prone to blockage from suspension formulations (Stein) and that suspension formulations required relatively large orifice diameters in order to avoid blockage (Nicolini), which would have deterred one of ordinary skill in the art from selecting an orifice diameter between the range of 0.16 to 0.29 mm for use in a pMDI com-rising epinephrine or a vaccine in suspension. However, Stein and Nicolini (along with the others) are references that are brought in by the applicant that were never used in the original rejections. The references used to reject claims 1, 40, and 76 are Gnopeck and Brambilla. The teaching away has to come from one of the references used in the rejection. A small diameter may be a problem for Stein, but Brambilla does not state that its claimed diameter range is not suitable for an epinephrine or vaccine in suspension and Gnopeck does not teach away from a smaller diameter as it does not state that the epinephrine in suspension formulation can only be used with a specific diameter. Gnopeck teaches epinephrine and a vaccine in suspension but does not disclose the range of diameter, while Brambilla does disclose the diameter, therefore it would be obvious to take the diameter of Brambilla and apply it to Gnopeck as one of ordinary skill in the art would experiment with different diameters to try and provide a flow profile that suits the medicine and the user. It is well known within the art to try different diameters for the administration of certain particulate drug formulations.
Furthermore, 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).
Conclusion
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/ROHAN PATEL/Examiner, Art Unit 3785
/BRANDY S LEE/Supervisory Patent Examiner, Art Unit 3785
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