DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Status of Claims
Claims 1-61 are cancelled. Claims 62-81 are pending.
Election/Restrictions
Applicant’s election without traverse of Group II, claims 70-81, in the reply filed on 01 December 2025 is acknowledged.
Claims 62-69 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 01 December 2025.
Claims 70-81 are examined herein to the extent that the propellant is HFA-134a, the corticosteroid is budesonide, and the short-acting beta agonist is albuterol, e.g., applicant's elected species.
Information Disclosure Statement
The information disclosure statement (IDS) filed 10/11/2023 and 07/24/2024 have been considered by the Examiner. A signed and initialed copy of the IDS is included with the instant Office Action.
Claim Rejections - 35 USC § 103
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under pre-AIA 35 U.S.C. 103(a) 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 under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
Claims 70-76 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over WEERS (WO 01/85136 A2, date of publication of 15 November 2001) in view of WOOLFE (US 2002/0081266 A1, date of publication of 27 June 2002, cited in IDS filed 10/11/2023).
Weers is primarily directed towards phospholipid based powders for drug delivery, preferably administered via inhalation (abstract).
Regarding claims 70-74 and 76, Weers discloses dry powder compositions of phospholipid for drug delivery (page 4, lines 3-6 and 34-35). Weers discloses that actives useful in the composition includes albuterol sulfate and budesonide (page 6, lines 17-33). Weers discloses that the phospholipid content is determined by the drug activity, the mode of delivery, and other factors and will be in the range from about 20% to up to 99.9% w/w and the drug loading is between about 0.1% and 80% w/w (page 9, lines 11-14). The amount of phospholipid (e.g., suspending particles) to the active amount of from about 20% to up to 99.9% w/w to between about 0.1% and 80% w/w (e.g., about 99,900:1 (e.g., 99.9%/0.1%) to about 1:4 (e.g., 20%/80%)) overlaps the range of “from above 1:1 and up to 200:1” (e.g., claim 73) and includes ranges where the total mass of the phospholipid (e.g., suspending particles) is greater than the total mass of the active. Thus, the claims are rendered prima facie obvious. See In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). See also MPEP 2144.05. Weers discloses that the particulate compositions can contain a combination of two or more active ingredients (page 10, lines 26-27). Weers discloses that the particulate compositions including without an associated agent (e.g., without an active agent) can be combined with one or more conventional micronized active agents (page 11, lines 1-2). Weers discloses that the particles have a mass median aerodynamic diameter preferably from about 0.5-5.0 µm (e.g., respirable) (page 12, lines 31-33). The mass median aerodynamic diameter preferably from about 0.5-5.0 µm lies inside the range of “between 10 µm and 500 nm” recited in claim 74. Thus, the range is rendered prima facie obvious. See also MPEP 2144.05 (quoted supra). Weers discloses that the particles are hollow and porous (e.g., perforated microstructures) (page 14, lines 6-10). Weers discloses that the active agent can be incorporated in the form of a solid particulate dispersion (page 18, lines 9-10). Weers discloses a composition for a metered dose inhaler that contains the powder in propellant including HFA-134a (page 27, lines 10-21).
Weers does not specifically teach the active is a combination of budesonide and albuterol and that the active are respirable active agent particles (e.g., claim 1). The deficiencies are made up for by the teachings of Woolfe.
Woolfe is primarily directed towards formulation for pulmonary or nasal administration comprising a mixture of particles of two or more drugs (abstract).
Regarding claims 70-72 and 75-76, Woolfe teaches that if symptoms of asthma are not well enough controlled by a β2 agonist then a steroid is added (paragraph [0005]). Woolfe teaches that β2 agonist includes salbutamol (e.g. albuterol) and steroids including budesonide (paragraph [0006]). Woolfe teaches that for inhalation the particle size is normally controlled to a mass mean diameter of 1-5 microns (e.g., respirable) (paragraph [0012]).
It would have been prima facie obvious to the person of ordinary skill in the art at the time the invention was made to produce a composition comprising a propellant including HFA-134a, particles comprising phospholipid including DSPC and calcium chloride, and active particles of albuterol and a steroid including budesonide; wherein the amount of the phospholipid is from about 20% to up to 99.9% w/w; wherein the amount of the active particles is between about 0.1% and 80% w/w; wherein the particles comprising phospholipid including DSPC and calcium chloride have a mass median aerodynamic diameter preferably from about 0.5-5.0 µm (e.g., respirable); wherein the active particles have a mass mean diameter of 1-5 microns (e.g., respirable); wherein the particles comprising phospholipid including DSPC and calcium chloride are hollow and porous (e.g., perforated microstructures). The person of ordinary skill in the art would have been motivated to make those modifications to obtain a composition to control asthma when β2 agonist (e.g., albuterol) does not control asthma well enough by including a steroid with the β2 agonist (e.g., albuterol), as taught by Woolfe. The person of ordinary skill in the art would have reasonably expected success because Weers discloses dry powder compositions of phospholipid for drug delivery (page 4, lines 3-6 and 34-35). Weers discloses that actives useful in the composition includes albuterol sulfate and budesonide (page 6, lines 17-33). Weers discloses that the phospholipid content is determined by the drug activity, the mode of delivery, and other factors and will be in the range from about 20% to up to 99.9% w/w and the drug loading is between about 0.1% and 80% w/w (page 9, lines 11-14). Weers discloses that the particulate compositions can contain a combination of two or more active ingredients (page 10, lines 26-27). Weers discloses that the particulate compositions including without an associated agent (e.g., without an active agent) can be combined with one or more conventional micronized active agents (page 11, lines 1-2). Weers discloses that the particles have a mass median aerodynamic diameter preferably from about 0.5-5.0 µm (e.g., respirable) (page 12, lines 31-33). Weers discloses that the particles are hollow and porous (e.g., perforated microstructures) (page 14, lines 6-10). Weers discloses that the active agent can be incorporated in the form of a solid particulate dispersion (page 18, lines 9-10). Weers discloses a composition for a metered dose inhaler that contains the powder in propellant including HFA-134a (page 27, lines 10-21). Woolfe teaches that if symptoms of asthma are not well enough controlled by a β2 agonist then a steroid is added (paragraph [0005]). Woolfe teaches that β2 agonist includes salbutamol (e.g. albuterol) and steroids including budesonide (paragraph [0006]). Woolfe teaches that for inhalation the particle size is normally controlled to a mass mean diameter of 1-5 microns (e.g., respirable) (paragraph [0012]).
Claims 77-80 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Weers in view of Woolfe as applied to claims 70-76 above, and further in view of BRODKA-PFEIFFER (US 2004/0052734 A1, date of publication of 18 March 2004).
Regarding claims 77-80, the composition of claim 76 is described above in section 8.
Weers and Woolfe do not specifically teach that the albuterol or the pharmaceutically acceptable salt thereof is present in crystalline or substantially crystalline form. The deficiency is made up for by the teachings of Brodka-Pfeiffer.
Brodka-Pfeiffer is primarily directed towards providing a stable crystalline form of a fine-milled salbutamol sulfate for inhalation (abstract).
Regarding claim 77, Brodka-Pfeiffer teaches stable crystalline form of a fine-milled salbutamol sulfate that can be produced, stored and used while maintaining the aerodynamic properties required for inhalation (paragraph [0014]).
Regarding claim 78, Weers discloses particles with DSPC as the phospholipid and calcium chloride (page 21, lines 24-26).
Regarding claim 79, Weers discloses that the phospholipid content is determined by the drug activity, the mode of delivery, and other factors and will be in the range from about 20% to up to 99.9% w/w and the drug loading is between about 0.1% and 80% w/w (page 9, lines 11-14). The amount of phospholipid (e.g., suspending particles) to the active amount of from about 20% to up to 99.9% w/w to between about 0.1% and 80% w/w (e.g., about 99,900:1 (e.g., 99.9%/0.1%) to about 1:4 (e.g., 20%/80%)) overlaps the range of “between 10 and 200” (e.g., claim 79). Thus, the range is rendered prima facie obvious. See also MPEP 2144.05 (quoted supra).
Regarding claim 80, Weers discloses phospholipid and calcium chloride particles with volume weight mass median diameters, that are determined using a laser diffraction analyzer, of including 1.7 µm (page 25, lines 22-23 ; Table III). The volume weight mass median diameter of 1.7 µm lies inside the range of between 0.2 µm and 50 µm recited in claim 80. Thus, the range is rendered prima facie obvious. See also MPEP 2144.05 (quoted supra).
It would have been prima facie obvious to the person of ordinary skill in the art at the time the invention was made to produce a composition comprising a propellant including HFA-134a, particles comprising phospholipid including DSPC and calcium chloride, and active particles of albuterol and a steroid including budesonide; wherein the amount of the phospholipid is from about 20% to up to 99.9% w/w; wherein the amount of the active particles is between about 0.1% and 80% w/w; wherein the particles comprising phospholipid including DSPC and calcium chloride have a mass median aerodynamic diameter preferably from about 0.5-5.0 µm (e.g., respirable); wherein the active particles have a mass mean diameter of 1-5 microns (e.g., respirable); wherein the particles comprising phospholipid including DSPC and calcium chloride are hollow and porous (e.g., perforated microstructures); wherein the albuterol is stable crystalline form. The person of ordinary skill in the art would have been motivated to make those modifications to obtain a composition with albuterol that is stable by including the albuterol taught by Brodka-Pfeiffer. The person of ordinary skill in the art would have reasonably expected success because Brodka-Pfeiffer teaches stable crystalline form of a fine-milled salbutamol sulfate that can be produced, stored and used while maintaining the aerodynamic properties required for inhalation (paragraph [0014]).
Claims 81 is rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Weers in view of Woolfe as applied to claims 70-76 above, further in view of Brodka-Pfeiffer as applied to claims 77-80 above, and further in view of MUSA (EP 1944018 A1, date of publication of 16 July 2008).
Regarding claim 81, the composition of claim 80 is described above in section 9.
Weers, Woolfe and Brodka-Pfeiffer do not specifically teach that at least 90% of the respirable active agent particles by volume exhibit an optical diameter of 7 µm or less. The deficiency is made up for by the teachings of Musa.
Musa is primarily directed towards micronized particles of an active used for inhalation (abstract).
Regarding claim 81, Musa teaches that although micronization of the drug is essential for deposition into the lower respiratory tract during inhalation, the finer are the particles, the stronger are the cohesion forces that favor the formation of agglomerates (paragraph [0011]). Musa teaches particles with at least 90% of the particles having a volume diameter including more preferably lower than 6 micron that avoids formation of stable agglomerates (paragraph [0039]). Musa teaches that the micronized particles can include budesonide (paragraph [0059]).
It would have been prima facie obvious to the person of ordinary skill in the art at the time the invention was made to produce a composition comprising a propellant including HFA-134a, particles comprising phospholipid including DSPC and calcium chloride, and active particles of albuterol and a steroid including budesonide; wherein the amount of the phospholipid is from about 20% to up to 99.9% w/w; wherein the amount of the active particles is between about 0.1% and 80% w/w; wherein the particles comprising phospholipid including DSPC and calcium chloride have a mass median aerodynamic diameter preferably from about 0.5-5.0 µm (e.g., respirable); wherein the active particles have a mass mean diameter of 1-5 microns (e.g., respirable); wherein the particles comprising phospholipid including DSPC and calcium chloride are hollow and porous (e.g., perforated microstructures); wherein the albuterol is stable crystalline form. The person of ordinary skill in the art would have been motivated to make those modifications to obtain a composition with active particles that avoids formation of stable agglomerates by including having at least 90% of the particles have a volume diameter lower than including 6 micron, as taught by Musa. The person of ordinary skill in the art would have reasonably expected success because Musa teaches that although micronization of the drug is essential for deposition into the lower respiratory tract during inhalation, the finer are the particles, the stronger are the cohesion forces that favor the formation of agglomerates (paragraph [0011]). Musa teaches particles with at least 90% of the particles having a volume diameter including more preferably lower than 6 micron that avoids formation of stable agglomerates (paragraph [0039]). Musa teaches that the micronized particles can include budesonide (paragraph [0059]).
Thus, the claimed invention as a whole is clearly prima facie obvious over the teachings of the prior art.
Conclusion and Correspondence
No claims are found allowable.
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/John P Nguyen/
Examiner, Art Unit 1619
/ANNA R FALKOWITZ/Primary Examiner, Art Unit 1600