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 .
Response to Amendments
The Amendment filed 5/13/2026 has been entered. Claims 1-2, 6-7, 11, 14-15, 41, and 44-45 were amended, and claims 16-40 were canceled. Thus, claims 1-15 and 41-45 are pending in the application.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-15 and 41-45 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention.
Regarding claim 1, the limitation “a housing sealed about a lower portion thereof” (ln. 8) is unclear as to what the word “thereof” is referring. For the purposes of examination, the term “thereof” will be interpreted as referring to the lower portion of the medicine cup reservoir. Additionally, the limitation “between greater than 0.9 mg/min and greater than 4.3 mg/min” in line 21 is unclear how the concentration is both “greater” and “between” the concentration values. For the purposes of examination, the claim limitation with be interpreted as requiring a delivered dose range between 0.9-4.3 mg/min.
Regarding claim 44, the limitation “a respirable dose rate” in line 2 is confusing, as it is unclear whether this limitation is meant to be the same as or different from “a respirable dose rate” recited in claim 1.
Regarding claim 45, the claim is unclear if only the improvement to the combination is required by the scope of the claim (i.e. “the improvement comprising…” in lines 19-26), or if the details of the aqueous solution of pirfenidone (ln. 4-18) is also required by the scope of the claim. For purposes of examination, all parts of the claim will be interpreted as required by the scope of the claim. However, the limitations directed to the “aqueous solution of pirfenidone” (ln. 4-18) will be taken as part of the “preamble” and conventional or known in the art. See MPEP 608.01(m) and 37 CFR 1.75(e). The “improvement comprising” portion of the claim is considered the “new or improved portion” alleged by the applicant. Additionally, the limitation “between greater than 0.9 mg/min…and greater than 4.3 mg/min” in lines 24-25 is unclear how the concentration is both “greater” and “between” the concentration values. For the purposes of examination, the claim limitation with be interpreted as requiring a delivered dose range between 0.9-4.3 mg/min, and a pirfenidone solution concentration between 4.0-19 mg/ml.
Any remaining claims are rejected as being dependent upon a rejected base claim.
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 of this title, 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.
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, 5-8, 13-15, 41, and 44-45 are rejected under 35 U.S.C. 103 as being unpatentable over Gallem et al (2008/0006264) in view of Denyer et al (2003/0146300) and Surber (2012/0192861).
Regarding claim 1, as best understood, Gallem discloses a drug-device combination of an aqueous solution and a nebulizer (Fig. 4A depicts a nebulizer 100 containing an aqueous solution within a liquid reservoir 102; See annotated Fig. 4A below for convenience) comprising:
(a) an aqueous solution disposed in a reservoir of a liquid nebulizer (Fig. 4A depicts an aqueous solution disposed in reservoir 102 or nebulizer 100); and
(b) the liquid nebulizer comprising:
(1) a medicine cup reservoir with a head space (Fig. 4A depicts a reservoir 102 having head space located above the surface of the aqueous liquid within the reservoir);
(2) a housing sealed about a lower portion thereof (Fig. 4A depicts walls of the nebulizer 100 forming a housing. Portions of these walls form the lower portion of reservoir 102 and “seal” the reservoir to prevent its aqueous solution from leaking);
(3) an opening for receiving the aqueous solution (Annotated Fig. 4A labels the opening of reservoir 102 formed by the housing walls of nebulizer 100);
(4) a closure for containing the aqueous solution in the medicine cup reservoir (Fig. 4A depicts a cap or closure that covers the opening of reservoir 102); and
(6) an aerosol generator comprising a vibrating mesh membrane disposed between the medicine cup reservoir and an aerosol mixing chamber (Fig. 4A aerosol generator 4 comprises a vibrating mesh membrane 3 that is configured to vibrate by oscillation generator 5; see [0031]. The membrane 3 is located between the reservoir 102 and a mixing chamber 103), wherein the aqueous solution is in fluid contact with the vibrating mesh membrane, wherein the vibrating mesh membrane is configured to operate at a predetermined frequency to convert the aqueous solution in the medicine cup reservoir into an aerosol in the aerosol mixing chamber ([0031] discloses that if a control signal is supplied to the membrane aerosol generator, membrane 3 will oscillate (at some frequency) and the liquid to be nebulized with be transported from the liquid side (i.e. reservoir 102) to the aerosol side (i.e. mixing chamber 103) of the membrane 3); wherein the liquid nebulizer is configured to deliver a respirable dose rate for a particular concentration of the solution to thereby deliver a respirable dose (Fig. 4A, the liquid solution must inherently have some concentration, the aerosol must inherently be delivered at some rate, and the result is some amount of respirable dose being delivered to the patient).
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Gallem does not disclose: (1) the reservoir is vented by a vent pathway connecting the head space of the medicine cup reservoir to ambient pressure; or (2) the solution is pirfenidone solution, wherein the nebulizer is configured to deliver at a dose rate between 0.9-4.3 mg/min for a pirfenidone concentration between 4.0-19.0 mg/ml to result in a dose of at least 7 mg of pirfenidone.
However, Denyer teaches a vented nebulizing metering chamber comprising a reservoir (Fig. 7, reservoir 21. See annotated Fig. 7 below) that includes a vented pathway connecting a head space of the reservoir to ambient pressure (Fig. 7, central hole 26 serves as a filling hole and also a vent hole; see [0051]). This vented pathway allows the liquid level within the metering chamber to fall as the liquid is atomized by allowing air to enter the fluid reservoir (see [0052]).
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Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the closure of the reservoir of Gallem to have a vent pathway as taught by Denyer. Having a vented pathway allows the pressure in the reservoir to be maintained at ambient pressure, thereby allowing the liquid level within the reservoir to fall as liquid is atomized.
The modified combination of Gallem does not have the liquid solution as pirfenidone solution, wherein the nebulizer is configured to deliver a respirable dose rate between 0.9-4.3 mg/min for a concentration of the pirfenidone solution between 4.0-19.0 mg/ml to deliver a dose of at least 7 mg of pirfenidone.
However, Surber teaches the use of pirfenidone formulation to treat fibrotic and inflammatory diseases of the lungs (See abstract). Surber teaches dispensing pirfenidone from a liquid nebulizer ([0015]), wherein the pirfenidone has a concentration between 15-50 mg/mL and at an effective dosage output rate between 0.1-1 mL/min, which is equivalent to 1.5-15 mg/mL if the low end of 15 mg/mL is chosen (See [0015]-[0016]). Additionally, Surber teaches a final respirable dose of at least 7 mg of pirfenidone ([0016] discloses a pirfenidone dose of 0.1-360 mg).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to configure the modified combination of Gallem to deliver a pirfenidone solution at a concentration between 4.0-19.0 mg/ml and at a dose rate between 0.9- 4.3 mg/min for a total dose of at least 7 mg of pirfenidone as taught by Surber. Surber teaches that delivery and such a rate and concentration is effective for treating fibrotic and inflammatory diseases of the lungs (Abstract).
Regarding claim 5, the modified combination of Gallem has the vent pathway traversing the closure to connect the interior of the medicine cup reservoir to ambient air (Denyer, Figs. 7-9, central hole 26 traverses the lid 25, as would be implemented in the modified combination of Gallem).
Regarding claim 6, the modified combination of Gallem has the vent pathway connecting the head space of the medicine cup reservoir to ambient pressure proximate to a portion of the housing engaged by the closure (Denyer, Figs. 7-9, central hole 26 connects the head space of the reservoir to ambient at the center of the lid 25, as would be implemented in the modified combination of Gallem. The center of the lie is considered “proximate” to the portion of the housing that is engaged by the lid/closure).
Regarding claim 7, the modified combination of Gallem does not explicitly disclose that the nebulizer is configured to deliver a respirable dose output rate does not decrease during operation of the aerosol generator.
However, not having the respirable dose output rate decrease during operation of the aerosol generator is considered obvious to try. See MPEP 2143(I)(E). Surber teaches that there is a recognized problem of needing to treat fibrotic and inflammatory diseases and proposes the use of pirfenidone formulation (Abstract). Surber additionally suggests a number of different respirable dose delivery rates of pirfenidone to be effective with such a treatment (see [0015]). During delivery of the pirfenidone solution, there are only a finite number of identified, predictable potential solutions when it comes to the rate at which the pirfenidone is delivered during a treatment session - (1) The dose rate remains steady throughout the treatment; (2) The dose rate decreases during treatment; or (3) The dose rate increases during treatment. One of ordinary skill in the art would have pursued any one of these treatment procedures to determine which would result in the best outcome for treating the patient.
Regarding claim 8, the modified combination of Gallem has the pirfenidone in the aqueous solution deuterated (Surber, [0338], discloses that the formulation can be a deuterated pirfenidone compound).
Regarding claim 13, the modified combination of Gallem has the vent pathway occluded (Denyer, Figs. 7-9, central hole 26 is occluded by air vent 28 to prevent spillage; see [0051]).
Regarding claim 14, the modified combination of Gallem has the occluded pathway comprising an alignment of the housing and the closure (Denyer, Fig. 9, air vent 28 and the housing of the reservoir 21 have the same longitudinal axis, whereby the two components are considered in “alignment”).
Regarding claim 15, the modified combination of Gallem has the occluded vent pathway comprised of a blocking member with a surrounding structure of the vent pathway (Denyer, Figs. 7-9, air vent 28 is a “blocking member” that sits within the surrounding walls of central hole 26).
Regarding claim 41, the modified combination of Gallem has a daily dose of the aqueous pirfenidone solution greater than 25 mgs of pirfenidone (Surber, [0243], discloses a respirable delivered daily dose of pirfenidone of 25 mg).
Regarding claim 44, as best understood, the modified combination of Gallem does not explicitly disclose a respirable dose rate of the aqueous pirfenidone solution increasing during the duration of inhalation by the patient.
However, increasing the delivered dose rate during the duration of inhalation by the patient is considered obvious to try. See MPEP 2143(I)(E). Surber teaches that there is a recognized problem of needing to treat fibrotic and inflammatory diseases and proposes the use of pirfenidone formulation (Abstract). Surber additionally suggests a number of different respirable dose rates of pirfenidone to be effective with such a treatment (see [0015]). During delivery of the pirfenidone solution, there are only a finite number of identified, predictable potential solutions when it comes to the rate at which the pirfenidone is delivered during the duration of inhalation by the patient - (1) The dose rate remains steady throughout inhalation; (2) The dose rate decreases during inhalation; or (3) The dose rate increases during inhalation. One of ordinary skill in the art would have pursued any one of these treatment procedures to determine which would result in the best outcome for treating the patient.
Regarding claim 45, Gallem discloses in a drug-device combination of an aqueous solution and a nebulizer used to deliver a dose of an aerosol (Fig. 4A depicts a nebulizer 100 containing an aqueous solution within a liquid reservoir 102), wherein the liquid reservoir is a sealed reservoir having a sealing closure (Fig. 4A, reservoir 102 is sealed by the housing of the nebulizer and a closure as annotated in Fig. 4A above) and the reservoir places the solution in fluid communication with an aerosol generator having a vibrating mesh membrane to produce an aerosol of the aqueous solution (Fig. 4A, the liquid of reservoir 102 is placed in contact with vibrating mesh membrane 3 of the aerosol generator 4);
an improvement comprising providing a headspace in a medicine cup reservoir of the nebulizer (Annotated Fig. 4A above depicts a reservoir 102 having head space located above the surface of the aqueous liquid within the reservoir) and providing an enlarged internal volume of an aerosol mixing chamber (Fig. 4A, aerosol mixing chamber 103 is an “enlarged internal volume).
Gallem does not disclose: (1) the improvement comprising using a vent pathway to maintain ambient pressure in the headspace; or (2) the solution is pirfenidone solution, wherein the nebulizer is configured to deliver at a dose rate between 0.9-4.3 mg/min for a pirfenidone concentration between 4.0-19.0 mg/ml to result in a dose of at least 7 mg of pirfenidone. It is noted that the remainder of the details regarding the specifics of the aqueous pirfenidone solution are considered conventional or known in the art as admitted by the applicant due to the “improvement-type” formatting of the claim. See 35 USC 112(b) rejection of claim 45 above for a detailed explanation.
However, Denyer teaches a vented nebulizing metering chamber comprising a reservoir (Fig. 7, reservoir 21. See annotated Fig. 7 below) that includes a vented pathway connecting a head space of the reservoir to ambient pressure (Fig. 7, central hole 26 serves as a filling hole and also a vent hole; see [0051]). This vented pathway allows the liquid level within the metering chamber to fall as the liquid is atomized by allowing air to enter the fluid reservoir (see [0052]).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the closure of the reservoir of Gallem to have a vent pathway as taught by Denyer. Having a vented pathway allows the pressure in the reservoir to be maintained at ambient pressure, thereby allowing the liquid level within the reservoir to fall as liquid is atomized.
The modified combination of Gallem does not have the liquid solution as pirfenidone solution, wherein the nebulizer is configured to deliver at a dose rate between 0.9-4.3 mg/min for a pirfenidone concentration between 4.0-19.0 mg/ml to result in a dose of at least 7 mg of pirfenidone.
However, Surber teaches the use of pirfenidone formulation to treat fibrotic and inflammatory diseases of the lungs (See abstract). Surber teaches dispensing pirfenidone from a liquid nebulizer ([0015]), wherein the pirfenidone has a concentration between 15-50 mg/mL and at an effective dosage output rate between 0.1-1 mL/min, which is equivalent to 1.5-15 mg/mL if the low end of 15 mg/mL is chosen (See [0015]-[0016]). Additionally, Surber teaches a final respirable dose of at least 7 mg of pirfenidone ([0016] discloses a pirfenidone dose of 0.1-360 mg).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to configure the modified combination of Gallem to deliver a pirfenidone solution at a concentration between 4.0-19.0 mg/ml and at a dose rate between 0.9- 4.3 mg/min for a total dose of at least 7 mg of pirfenidone as taught by Surber. Surber teaches that delivery and such a rate and concentration is effective for treating fibrotic and inflammatory diseases of the lungs (Abstract).
In the alternative interpretation that the details regarding the specifics of the aqueous pirfenidone solution are not considered conventional or known in the art, Surber additionally teaches the pirfenidone solution have a volume between 0.5-10 mLs (Table 12 discloses a “nebulizer volume” of 3.85), an osmolality between 50-1000 mOsmol/L ([0034]), a salt concentration between 0.30-150mM ([0034]), a pH between 3.0-7.0 ([0005]), the liquid reservoir containing a volume between 05.-10 mLs (Table 12), a volumetric mean diameter (VMD) between 2-5 microns (Table 12), a geometric standard deviation (GSD) of emitted droplet size distribution between 1.0-3.4 (Table 12), a fine particle fraction (FPF) at least 45% (Table 12), and a nebulizer rate of at least 0.5 mL/min (Table 12) which would result in converting the entire volume of solution to an aerosol in about 8 minutes (3.85 mL total at a rate of 0.5 mL/min), which is between 1-20 minutes.
Claims 2 and 11-12 are rejected under 35 U.S.C. 103 as being unpatentable over Gallem et al in view of Denyer and Surber, as applied to claim 1 above, and further in view of Stangl (8,387,895).
Regarding claim 2, the modified combination of Gallem has the nebulizer configured to generate an aerosol of the aqueous solution of pirfenidone having a volumetric mean diameter less than 5 microns (Surber, [0016], discloses 1-5 microns).
The modified combination of Gallem does not state the internal volume of the mixing chamber.
However, Stangl teaches a nebulizer comprising a mixing chamber having a volume between 60 -120 mL (cc) ((Fig. 1, nebulizer 1 has a mixing chamber 3. The abstract discloses the volume of the mixing chamber 3). This specific size of the mixing chamber allows continuously generated aerosol to accumulate therein without losses even when a patient’s exhalation phase is longer than their inhalation phase (Abstract).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to design the size of the mixing chamber of the modified combination of Gallem to be between 60-120 mL (i.e. greater than 49 cc) as taught by Stangl. Such a mixing chamber size allows continuously generated aerosol to accumulate within the mixing chamber without losses even when a patient’s exhalation phase is longer than their inhalation phase.
Regarding claim 11, the modified combination of Gallem does not state the internal volume of the mixing chamber.
However, Stangl teaches a nebulizer comprising a mixing chamber having a volume between 60 -120 mL (cc) ((Fig. 1, nebulizer 1 has a mixing chamber 3. The abstract discloses the volume of the mixing chamber 3). This specific size of the mixing chamber allows continuously generated aerosol to accumulate therein without losses even when a patient’s exhalation phase is longer than their inhalation phase (Abstract).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to design the size of the mixing chamber of the modified combination of Gallem to be between 60-120 mL (i.e. between 49-120cc) as taught by Stangl. Such a mixing chamber size allows continuously generated aerosol to accumulate within the mixing chamber without losses even when a patient’s exhalation phase is longer than their inhalation phase.
Regarding claim 12, the modified combination of Gallem does not state the internal volume of the mixing chamber.
However, Stangl teaches a nebulizer comprising a mixing chamber having a volume between 60 -120 mL (cc) ((Fig. 1, nebulizer 1 has a mixing chamber 3. The abstract discloses the volume of the mixing chamber 3). This specific size of the mixing chamber allows continuously generated aerosol to accumulate therein without losses even when a patient’s exhalation phase is longer than their inhalation phase (Abstract).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to design the size of the mixing chamber of the modified combination of Gallem to be between 60-120 mL (i.e. between 98-140 cc) as taught by Stangl. Such a mixing chamber size allows continuously generated aerosol to accumulate within the mixing chamber without losses even when a patient’s exhalation phase is longer than their inhalation phase.
Claims 3 and 42-43 is rejected under 35 U.S.C. 103 as being unpatentable over Gallem et al in view of Denyer and Surber, as applied to claim 1 above, and further in view of Babaev (6,601,581).
Regarding claim 3, the modified combination of Gallem has the aerosol generator configured to convert between 0.5-10 mLs of the pirfenidone solution ([0010] discloses between 0.5 to 6 mL of pirfenidone solution) to aerosol droplets at a respirable delivered dose output rate of at least 2.8 mg per minute (Surber, [0015]-[0016] discloses both concentration and volume output rates that would result in such a dosage output rate).
The modified combination of Gallem does not have a patient operated control to initiate operation of the aerosol generator.
However, Babaev teaches a nebulizer (Fig. 2) comprising a liquid reservoir (Fig. 2, reservoir 19) and a vibrating aerosol generator (Fig. 2, piezo disk 15), wherein the aerosol generator is under patient operated control (Fig. 2, on/off button 21 activates the piezo disk 15 when pushed by the user).
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Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to design the nebulizer of the modified combination of Gallem to have an on/off control button as taught by Babaev to allow the user to have full control over operation of the nebulizer.
Regarding claim 42, the modified combination of Gallem has the respirable delivered dose output rate of the pirfenidone solution as greater than 2.8 mg pirfenidone per minute (Surber, [0015]-[0016] discloses ranges both concentration and volume output rates that would result in such a dosage output rate).
Regarding claim 43, the modified combination of Gallem has activation of the patient operated control drawing ambient air into the head space of the medicine cup reservoir (Denyer, Figs. 7-9, as the liquid level in the reservoir 21 drops due to activation of the nebulizer, ambient air will enter through vent 28; see [0052]).
Claims 9-10 are rejected under 35 U.S.C. 103 as being unpatentable over Gallem et al in view of Denyer and Surber, as applied to claim 1 above, and further in view of Borgschulte et al (2008/0308096).
Regarding claim 9, the modified combination of Gallem does not have the aerosol mixing chamber further comprising a one-way inspiratory valve.
However, Borgschulte teaches a nebulizer comprising an aerosol mixing chamber (see Annotated Fig. 9 below), wherein the aerosol mixing chamber has a one-way inspiratory valve (Fig. 9, inspiratory valves 9a and 9b).
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Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to design the mixing chamber of the modified combination of Gallem to have a one-way inspiratory valve to allow air to be drawn into the chamber to assist in the mixing of the generated aerosol.
Regarding claim 10, the modified combination of Gallem has the aerosol mixing chamber further comprises a mouthpiece sized for inhaled delivery of the aqueous solution of pirfenidone by a patient (Gallem, Fig. 4A, mouthpiece 104 is sized in such a manner).
The modified combination of Gallem does not have a one-way expiratory valve.
However, Borgschulte additionally teaches a one-way expiratory valve on the mouthpiece to allow exhaled air to exit the device if the patient exhales into the nebulizing chamber.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to design the mouthpiece of the modified combination of Gallem to have a one-way expiratory valve to allow exhaled air to exit the device to prevent pressure buildup within the mixing chamber.
Claims 1, 4, and 6 are rejected under 35 U.S.C. 103 as being unpatentable over Gallem et al (2008/0006264) in view of Hu (2014/0216443) and Surber (2012/0192861)
Regarding claim 1, Gallem discloses a drug-device combination of an aqueous solution and a nebulizer (Fig. 4A depicts a nebulizer 100 containing an aqueous solution within a liquid reservoir 102; See annotated Fig. 4A below for convenience) comprising:
(a) an aqueous solution disposed in a reservoir of a liquid nebulizer (Fig. 4A depicts an aqueous solution disposed in reservoir 102 or nebulizer 100); and
(b) the liquid nebulizer comprising:
(1) a medicine cup reservoir with a head space (Fig. 4A depicts a reservoir 102 having head space located above the surface of the aqueous liquid within the reservoir);
(2) a housing sealed about a lower portion thereof (Fig. 4A depicts walls of the nebulizer 100 forming a housing. Portions of these walls form the lower portion of reservoir 102 and “seal” the reservoir to prevent its aqueous solution from leaking);
(3) an opening for receiving the aqueous solution (Annotated Fig. 4A labels the opening of reservoir 102 formed by the housing walls of nebulizer 100);
(4) a closure for containing the aqueous solution in the medicine cup reservoir (Fig. 4A depicts a cap or closure that covers the opening of reservoir 102); and
(6) an aerosol generator comprising a vibrating mesh membrane disposed between the medicine cup reservoir and an aerosol mixing chamber (Fig. 4A aerosol generator 4 comprises a vibrating mesh membrane 3 that is configured to vibrate by oscillation generator 5; see [0031]. The membrane 3 is located between the reservoir 102 and a mixing chamber 103), wherein the aqueous solution is in into fluid contact with the vibrating mesh membrane, wherein the vibrating mesh membrane is configured to operate at a predetermined frequency to convert the aqueous solution in the medicine cup reservoir into an aerosol in the aerosol mixing chamber ([0031] discloses that if a control signal is supplied to the membrane aerosol generator, membrane 3 will oscillate (at some frequency) and the liquid to be nebulized with be transported from the liquid side (i.e. reservoir 102) to the aerosol side (i.e. mixing chamber 103) of the membrane 3); wherein the nebulizer is configured to deliver the aerosol at a delivered dose rate for a particular concentration of the solution to thereby deliver a respirable dose (Fig. 4A, the liquid solution must inherently have some concentration, the aerosol must inherently be delivered at some rate, and the result is some amount of respirable dose being delivered to the patient).
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Gallem does not disclose: (1) the reservoir is vented by a vent pathway connecting the head space of the medicine cup reservoir to ambient pressure; or (2) the solution is pirfenidone solution, wherein the liquid nebulizer is configured to deliver a respirable dose rate between 0.9-4.3 mg/min for a concentration of the pirfenidone solution between 4.0-19.0 mg/ml to result in a dose of at least 7 mg of pirfenidone.
However, Hu teaches nebulizer (Fig. 5) comprising a liquid reservoir (Fig. 5, liquid container 1), wherein the liquid container is vented (Fig. 5, fluid recycle system 13 allows aerosolized spray to be recycled via a first opening 134 and a second opening 135 that connect the liquid reservoir to the mixing chamber and ambient air via mouthpiece 132).
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Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the housing of the modified combination of Gallem to have two openings and a channel that connect the mixing chamber to the reservoir as taught by Hu. This connection would allow for recycling of aerosol that condenses in the mixing chamber as well as result in the reservoir being connected to ambient pressure.
The modified combination of Gallem does not have the liquid solution as pirfenidone solution, wherein the nebulizer is configured to deliver a respirable dose rate between 0.9-4.3 mg/min for a concentration of pirfenidone solution between 4.0-19.0 mg/ml to result in a dose of at least 7 mg of pirfenidone.
However, Surber teaches the use of pirfenidone formulation to treat fibrotic and inflammatory diseases of the lungs (See abstract). Surber teaches dispensing pirfenidone from a liquid nebulizer ([0015]), wherein the pirfenidone has a concentration between 15-50 mg/mL and at an effective dosage output rate between 0.1-1 mL/min, which is equivalent to 1.5-15 mg/mL if the low end of 15 mg/mL is chosen (See [0015]-[0016]). Additionally, Surber teaches a final respirable dose of at least 7 mg of pirfenidone ([0016] discloses a pirfenidone dose of 0.1-360 mg).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to configure the modified combination of Gallem to deliver a pirfenidone solution at a concentration between 4.0-19.0 mg/ml and at a dose rate between 0.9- 4.3 mg/min for a total dose of at least 7 mg of pirfenidone as taught by Surber. Surber teaches that delivery and such a rate and concentration is effective for treating fibrotic and inflammatory diseases of the lungs (Abstract).
Regarding claim 4, the modified combination of Gallem has the vent pathway spaced away from the sealed lower portion of the housing and traverses the housing of the nebulizer to connect the headspace of the medicine cup reservoir cup to ambient air (Hu, Fig. 5, first vent opening 134 and second vent opening 135 are spaced away from the seal lower housing and traverses the housing of the nebulizer to connect the head space of the reservoir to ambient air).
Regarding claim 6, the modified combination of Gallem has the vent pathway connecting the head space of the medicine cup reservoir to ambient pressure proximate to a portion of the housing engaged by the closure (Hu, Fig. 5, second vent opening 135 would be located proximate to the closure in the modified combination of Gallem).
Response to Arguments
Applicant's arguments filed 5/13/2026 have been fully considered but they are not persuasive.
On page 9 in the “Specification Objections” and “Claim Objections” sections of the Applicant’s remarks, the Applicant argues that the specification and claims have been amended to overcome the objections of the previous office action. The Examiner agrees, and has thus withdrawn those objections.
On page 9 in the “Claim Rejections - 35 U.S.C. 112(b)” section of the Applicant’s remarks, the Applicant argues that the claims have been amended to overcome the 35 U.S.C. 112(b) rejections of the previous office action. The Examiner partially agrees, and has thus withdrawn those 35 U.S.C. 112(b) rejections which were addressed. However, the unaddressed 35 U.S.C. 112(b) rejections are being maintained as detailed above.
On pages 10-11 in the “A. The Claimed Nebulizer-Drug Combination Exhibits Unexpected Results” section of the Applicant’s remarks, the Applicant argues that their invention having a vent pathway achieves a significant and unexpected increase in the respirable dose output rate and deposition on lung tissue of the drug pirfenidone compared to a saline solution, where the vent pathway achieves a decrease in output rate with the saline solution, and thus exhibits unexpected results. However, the Examiner respectfully disagrees. According to the MPEP 716.02, allegations of unexpected results are meant to be from the differences between the Applicant’s invention and the closest prior art of record. As the Applicant has not provided any evidence comparing their invention with the closest prior art of record, the Applicant has not set forth sufficient evidence to support unexpected results. Thus, the current prior art of record can still be used to teach the Applicant’s claimed invention.
On page 11 in the “B. Gallen Teaches Neither a Vent Pathway Not the Use of a Pirfenidone Solution” section of the Applicant’s remarks, the Applicant argues that Gallem does not teach a vent pathway or a pirfenidone solution, nor the related reservoir pressure conditions and aerosolization performance including respirable dose output rate, and so cannot teach the Applicant’s claimed invention. However, the Examiner respectfully disagrees. 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, the vent pathway is taught by Denyer or Hu and the pirfenidone solution and aerosolization performance is taught by Surber as detailed in the 35 U.S.C. 103 rejections of claim 1 detailed above. Thus, the current prior art of record can still be used to teach the Applicant’s claimed invention.
On page 11 in the “B. Gallen Teaches Neither a Vent Pathway Not the Use of a Pirfenidone Solution” section of the Applicant’s remarks, the Applicant argues that Gallem does not recognize the problem of pressure changes occurring in a sealed reservoir during nebulization, and so does not provide the motivation to modify its system to include a vent pathway. However, the Examiner respectfully disagrees. Gallem is not used to provide the motivation for including a vent pathway, as this is instead drawn from the teaching references of Denyer or Hu used to provide the modification. Denyer teaches a vent pathway allows the pressure in the reservoir to be maintained at ambient pressure, thereby allowing the liquid level within the reservoir to fall as liquid is atomized (Denyer; Fig. 7; paras. [0051-0052]), while Hu teaches a vent pathway would allow for recycling of aerosol that condenses in the mixing chamber as well as result in the reservoir being connected to ambient pressure (Hu; Fig. 5; para. [0039]). Thus, the current prior art of record can still be used to teach the Applicant’s claimed invention.
On page 11 in the last paragraph to page 12 in the first paragraph of the Applicant’s remarks, the Applicant argues that the Denyer and Surber references fail to recognize the unexpected increase in dose output, and consequently the improved pharmacokinetics of the Applicant’s claimed nebulizer. However, the Examiner respectfully disagrees. Surber teaches the Applicant’s claimed dose output of a respirable dose rate between 0.9 mg/min-4.3 mg/min to deliver 7 mg of pirfenidone, as Surber teaches an effective dosage output rate of pirfenidone between 0.1-1 mL/min, which is equivalent to 1.5-15 mg/mL when the low end pirfenidone concentration of 15 mg/mL is chosen (See Surber paras. [0015]-[0016]) and a final respirable dose of at least 7 mg of pirfenidone (Surber para. [0016] discloses a pirfenidone dose of 0.1-360 mg). Thus, the current prior art of record can still be used to teach the Applicant’s claimed invention.
On page 12 in the second and third paragraphs of the Applicant’s remarks, the Applicant argues that Denyer does not teach maintaining the reservoir at ambient pressure as a functional objective but rather ensuring fluid continuity for the reservoir, and so cannot teach the Applicant’s claimed invention as it is directed to a fundamentally different problem. However, the Examiner respectfully disagrees. According to the MPEP 2144(IV), “The reason or motivation to modify the reference may often suggest what the inventor has done, but for a different purpose or to solve a different problem. It is not necessary that the prior art suggest the combination to achieve the same advantage or result discovered by applicant”. Therefore, even though the Denyer reference may teach a vent pathway for a different reason or to solve a different problem than the Applicant, the Denyer reference can still be used to teach the vent pathway as claimed. Thus, the current prior art of record can still be used to teach the Applicant’s claimed invention.
On page 12 in the fourth paragraph of the Applicant’s remarks, the Applicant argues that the combination of Denyer and Surber lacks a recitation of an aqueous solution of pirfenidone. However, the Examiner respectfully disagrees. Surber does teach an aqueous solution of pirfenidone (Surber para. [0015] recites, “the liquid nebulizer is characterized as having… the pirfenidone or pyridone analog compound administered to the mammal… emitted droplet size distribution of the aqueous solution…”). Thus, the current prior art of record can still be used to teach the Applicant’s claimed invention.
On page 12 in the fourth paragraph of the Applicant’s remarks, the Applicant argues that the Surber reference is silent with regards to the unexpected, synergistic benefit of using a nebulizer with a vent pathway to deliver pirfenidone, and so cannot be used to teach the Applicant’s claimed invention. However, the Examiner respectfully disagrees. 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, Gallem teaches the nebulizer structures as claimed save for the vent pathway taught by Denyer and the use of pirfenidone solution with related dosing parameters taught by Surber, and so this combination of prior art teaches the whole of the Applicant’s claim 1 invention. Moreover, as previously explained above, the Applicant has not provided evidence to prove there are unexpected results of using their claimed invention compared to the current prior art of record. Thus, the current prior art of record can still be used to teach the Applicant’s claimed invention.
On page 12 in the last paragraph of the Applicant’s remarks, the Applicant argues that the combination of prior art is grounded in impermissible hindsight reconstruction. However, the Examiner respectfully disagrees. In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). Thus, the current prior art of record can still be used to teach the Applicant’s claimed invention.
On page 13 in the “D. A Nexus Exists Between the Claimed Invention and the Evidence” section of the Applicant’s remarks, the Applicant argues that there is a clear nexus between the claimed subject matter and the demonstrated improvements attributable to unexpected results. However, the Examiner respectfully disagrees. As previously explained, the Applicant has not yet provided proof for their claimed invention having unexpected results in comparison to the prior art of record. As unexpected results have not yet been proven, an argument for a nexus of claimed limitations linked to unexpected results is moot. Thus, the current prior art of record can still be used to teach the Applicant’s claimed invention.
On page 13 in the “E. The Evidence Overcomes Any Alleged Motivation to Combine” section of the Applicant’s remarks, the Applicant argues that their claimed invention provides unexpected and synergistic results for respirable dose output and enhanced pharmacokinetic parameters not predicted by the teaching references, and so the current prior art of record cannot be used to teach the Applicant’s claimed invention. However, the Examiner respectfully disagrees. Firstly, Surber does teach the claimed respirable dose output and enhanced pharmacokinetic parameters, as Surber teaches the Applicant’s claimed dose output of a respirable dose rate between 0.9 mg/min-4.3 mg/min to deliver 7 mg of pirfenidone, an effective dosage output rate of pirfenidone between 0.1-1 mL/min which is equivalent to 1.5-15 mg/mL if the low end pirfenidone concentration of 15 mg/mL is chosen, and a final respirable dose of at least 7 mg of pirfenidone (Surber paras. [0015-0016]). Secondly, the Applicant has not provided evidence to prove there are unexpected results of using their claimed invention compared to the current prior art of record. Thus, the current prior art of record can still be used to teach the Applicant’s claimed invention.
On pages 13-16 in the “Claims 2, 3, 9-12, 14-15, and 42-45” and “Claims 1, 4, and 6” sections of the Applicant’s remarks, the Applicant argues that the current prior art of record cannot teach the Applicant’s claimed invention for the reasons set forth in Sections A-E above, such as the Applicant’s invention exhibiting unexpected results and the prior art failing to recognize the claimed performance advantages. However, the Examiner respectfully disagrees as previously explained in the above responses to the arguments in Sections A-E. Thus, the current prior art of record can still be used to teach the Applicant’s claimed invention.
On page 14 in the last paragraph to page 15 in the first paragraph of the Applicant’s remarks, the Applicant argues that Hu does not teach a vent pathway configured to maintain ambient pressure in the medicine cup reservoir headspace as Hu has a closed-loop fluid recirculation architecture of a fundamentally different objective different from the Applicant’s maintaining the headspace at a continuous ambient pressure throughout nebulization. However, the Examiner respectfully disagrees. Hu teaches a first opening 134 which is open to the ambient environment via the dispensing tube 132, wherein the first opening 134 fluidly communicates with a second opening 135 to the reception space 10 of liquid medicine, thereby allowing the ambient environment to fluidly communicate with the reception space 10 above the liquid medicine during use (Hu; Fig. 5; para. [0039]). Thus, the current prior art of record can still be used to teach the Applicant’s claimed invention.
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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/JACQUELINE M PINDERSKI/Examiner, Art Unit 3785
/RACHEL T SIPPEL/Primary Examiner, Art Unit 3785
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