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 .
DETAILED ACTION
1. This office action is in response to the preliminary amendment filed on 2/21/2023. As directed by the amendment, claims 1, 9, and 11 have been amended, claims 16-40 have been canceled, and claims 41-45 have been added. Thus, claims 1-15 and 41-45 are pending in the application.
Specification Objections
2. The disclosure is objected to because of the following informalities:
Paragraph [00159] is objected to for have a double period at the end of the sentence ending in “all of the periphery thereof..”
Appropriate correction is required.
Claim Interpretation- 35 USC § 112 – Sixth Paragraph/35 USC § 112(f)
3. The following is a quotation of 35 U.S.C. 112(f):
(f) Element in Claim for a Combination. – An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The following is a quotation of pre-AIA 35 U.S.C. 112, sixth paragraph:
An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art. The broadest reasonable interpretation of a claim element (also commonly referred to as a claim limitation) is limited by the description in the specification when 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is invoked.
As explained in MPEP § 2181, subsection I, claim limitations that meet the following three-prong test will be interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph:
(A) the claim limitation uses the term “means” or “step” or a term used as a substitute for “means” that is a generic placeholder (also called a nonce term or a non-structural term having no specific structural meaning) for performing the claimed function;
(B) the term “means” or “step” or the generic placeholder is modified by functional language, typically, but not always linked by the transition word “for” (e.g., “means for”) or another linking word or phrase, such as “configured to” or “so that”; and
(C) the term “means” or “step” or the generic placeholder is not modified by sufficient structure, material, or acts for performing the claimed function.
Use of the word “means” (or “step”) in a claim with functional language creates a rebuttable presumption that the claim limitation is to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites sufficient structure, material, or acts to entirely perform the recited function.
Absence of the word “means” (or “step”) in a claim creates a rebuttable presumption that the claim limitation is not to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is not interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites function without reciting sufficient structure, material or acts to entirely perform the recited function.
Claim limitations in this application that use the word “means” (or “step”) are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action. Conversely, claim limitations in this application that do not use the word “means” (or “step”) are not being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action.
At present, no limitations are interpreted under 35 USC 112(f).
Claim Objections
4. Claims 1, 6, 11, and 45 are objected to because of the following informalities:
Regarding claim 1, the term --and-- should be added after “nebulizer;” in line 3 to read --nebulizer; and--. Additionally, the phrase --the vented liquid nebulizer and comprising” (ln. 5) should read --the liquid nebulizer, the liquid nebulizer comprising-- for clarity and the sake of consistency with how the term “liquid nebulizer” is originally introduced within the claim. Additionally, the term “the medicine reservoir cup” (ln. 15) should read --the medicine cup reservoir-- the sake of consistency with how the term is originally introduced within the claim.
Regarding claim 6, the phrase “the portion of the housing” (ln. 3) should read --a portion of the housing-- because term “the portion” as not previously been introduced within the claims.
Regarding claim 11, the word “that” (ln. 2) appears as though it is a misspelling of --than--.
Regarding claim 45, the phrase “an aqueous solution of pirfenidone has” (ln. 3) should read -- an aqueous solution of pirfenidone having--. Additionally, the term “the solution” (ln. 9) should read -- the aqueous solution-- for the sake of consistency with how the term is originally introduced within the claim.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
5. 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.
6. 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 claim is unclear due to a lack of a transitional phrase (e.g. comprising, consisting of, etc). A transitional phrase is required to define the scope of a claim with respect to what unrecited additional components, if any, are excluded from the scope of the claim. See MPEP 2111.03. A suggestion for correction is --A drug-device combination of an aqueous pirfenidone solution and a nebulizer comprising:--. Additionally, 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 “wherein the aqueous solution of pirfenidone comes into fluid contact with the vibrating mesh membrane operating at a predetermined frequency to convert the aqueous pirfenidone solution in the medicine cup reservoir maintained at ambient pressure into a pirfenidone aerosol in the aerosol mixing chamber” (ln. 15-19) renders the claim unclear if it is directed towards a device or a method of using a device. A suggestion for correction is -- wherein the aqueous solution of pirfenidone 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 pirfenidone solution in the medicine cup reservoir maintained at ambient pressure into a pirfenidone aerosol in the aerosol mixing chamber--. Additionally, the term “the range of concentrations” (ln. 20) is unclear for lacking an antecedent basis. For the purposes of examination, the limitation will be interpreted as the respirable does rate for a concentration of pirfenidone solution. Additionally, the limitation “between greater than 0.9 mg/min…and greater than 4.3 mg/min” 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. Finally, the limitation “wherein the respirable delivered dose rate for the range of concentrations of the pirfenidone solution is between” (ln. 19-20) renders the claim unclear if it is directed towards a device or a method of using a device. A suggestion for correction is -- wherein the liquid nebulizer is configured to deliver a respirable dose rate for a concentration of the pirfenidone solution between--.
Regarding claim 2, the limitation “wherein the aerosol mixing chamber…contains an aerosol of the aqueous solution of pirfenidone having a volumetric mean diameter less than 5 microns” (ln. 1-4) renders the claim unclear if it is directed towards a device or a method of using a device. A suggestion for correction is --wherein the aerosol mixing chamber…and is configured to contain an aerosol of the aqueous solution of pirfenidone having a volumetric mean diameter less than 5 microns--.
Regarding claim 7, the limitation “wherein the respirable delivered dose output rate does not decrease during operation of the aerosol generator” (ln. 1-2) renders the claim unclear if it is directed towards a device or a method of using a device. A suggestion for correction is --wherein the nebulizer is configured to deliver a respirable dose output rate that does not decrease during operation of the aerosol generator--.
Regarding claim 11, the limitation “an internal volume between greater tha[n] 49 cubic centimeters and 120 cubic centimeters” (ln. 2-3) is unclear as to the upper bound of the phrase “between greater than 49 cubic centimeters and 120 cubic centimeters.” A suggestion for correction is -- an internal volume between 49 cubic centimeters and 120 cubic centimeters--.
Regarding claim 14, the term “the occluded pathway” (ln. 1-2) lacks an antecedent basis. Claim 14 is currently dependent upon claim 10, not claim 13 in which the term “occluded” is first introduced. For the purposes of examination, claim 14 will be interpreted as newly introducing the concept of the vent pathway being “occluded.”
Regarding claim 15, the term “the occluded vent pathway” (ln. 1-2) lacks an antecedent basis. Claim 15 is currently dependent upon claim 10, not claim 13 in which the term “occluded” is first introduced. For the purposes of examination, claim 15 will be interpreted as newly introducing the concept of the vent pathway being “occluded.”
Regarding claim 41, the limitation “wherein a daily dose of the aqueous pirfenidone solution is greater than 25 mgs of pirfenidone” (ln. 1-2) is unclear if the limitation is further limiting to the device of claim 1 is merely making a factual statement about aqueous pirfenidone solution. For the purposes of examination, the claim will be interpreted as the nebulizer being “configured to” deliver a daily dose of the aqueous pirfenidone solution that is greater than 25 mgs of pirfenidone.
Regarding claim 44, the limitation “wherein the respirable delivered dose rate of the aqueous pirfenidone solution increases during the duration of inhalation by the patient” (ln. 1-3) renders the claim unclear if it is directed towards a device or a method of using a device. A suggestion for correction is -- wherein the nebulizer is configured to deliver a respirable dose rate of the aqueous pirfenidone solution that increases during the duration of inhalation by the patient--.
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 18-24), or if the details of the aqueous solution of pirfenidone (ln. 3-17) 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. 3-17) 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” 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. Additionally, the limitation “using a vent pathway to maintain ambient pressure in a headspace of the medicine cup” (ln. 19-20) renders the claim unclear if it is directed towards a device or a method of using a device. A suggestion for correction is --a vent pathway configured to maintain ambient pressure in a headspace of the medicine cup--. Finally, the term “the medicine cup reservoir (ln. 19-20) lacks an antecedent basis. For the purposes of examination, the “the medicine cup reservoir” will be interpreted as initially introducing “a” medicine cup reservoir.
Any remaining claims are rejected as being dependent upon a rejected base claim.
Claim Rejections - 35 USC § 103
7. 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.
8. 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.
9. Claims 1, 5-8, 13, 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, 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) wherein:
(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);
(b) the liquid nebulizer and 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 reservoir cup 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 comes into fluid contact with the vibrating mesh membrane operating 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 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 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).
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 the 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 respirable delivered dose output rate does not decrease during operation of the aerosol generator.
However, not having the 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 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 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, the modified combination of Gallem does not explicitly disclose the respirable delivered 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 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 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 f 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.
10. 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.
11. 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]).
12. Claims 9-10 and 14-15 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.
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).
13. 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) wherein:
(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);
(b) the liquid nebulizer and 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 reservoir cup 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 comes into fluid contact with the vibrating mesh membrane operating 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 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, 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 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).
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 the 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).
Conclusion
14. The prior art made of record and not relied upon is considered pertinent to applicant's disclosure:
Boehm (2007/0181133), Gallem (2006/0207591), Yu (2015/0231660), and Muller (2018/0169713) disclose drug-device combinations comprising aqueous solutions in a medicine cup reservoir of liquid nebulizers, wherein the liquid nebulizers comprise aerosol generators having vibrating mesh membranes for atomizing the aqueous solutions.
15. Any inquiry concerning this communication or earlier communications from the examiner should be directed to TIMOTHY A STANIS whose telephone number is (571)272-5139. The examiner can normally be reached on Mon - Fri 8:30-5:00.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Justine Yu can be reached on 571-272-4835. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/TIMOTHY A STANIS/Primary Examiner, Art Unit 3785