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 .
Receipt is acknowledged of Amendments and Remarks filed on 12/15/25. Claims 1, 10 and 21 have been amended, no new claims have been added and claims 9, 11 and 24-25 have been canceled. Accordingly, claims 1, 3-8, 10, 12-14 and 21 are under examination on the merits.
Rejections and/or objections not reiterated from the previous Office Action are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set of rejections and/or objections presently being applied to the instant application.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The 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 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1, 3-8, 10, 12-14 and 21 are rejected under 35 U.S.C. 103 as being unpatentable over Hassan et al (WO 0051591 or US 20060009437) (Recitation from the US document) in combination with Ashurst et al (6,532,955), Corr et al (WO 2012156711) as evidenced by DAIKIN HFC-152a product information or UNFCCC (Global Warming Potentials).
Hassan et al teach a medicament containing (A) formoterol or a pharmaceutically acceptable salt thereof or a solvate of formoterol or a solvate of the salt and (B) mometasone furoate, for administration in the treatment of an inflammatory or obstructive airways disease. In particular, A and B are in a mixture in solution or suspension and the said formoterol is formoterol fumarate dihydrate (See abstract, [0004] and claims 1-5).
Hassan et al disclose that “It has now surprisingly been found that a significant unexpected therapeutic benefit, particularly a synergistic therapeutic benefit, in the treatment of inflammatory or obstructive airways diseases can be obtained by combination therapy using formoterol, in free form or in the form of a salt or solvate thereof, and mometasone furoate (See [0004]).
Hassan et al teach a pharmaceutical composition comprising a mixture of effective amounts of (A) and (B), optionally together with a pharmaceutically acceptable carrier (See [0008]).
Hassan et al disclose an aerosol composition suitable for use as the inhalable form of the medicament which may comprise the active ingredient in solution or dispersion in a propellant, which may be chosen from any of the propellants known in the art, such as hydrocarbons, and halogen-substituted hydrocarbons, including 1,1,1,2-tetrafluoroethane (HFA134a) and 1,1,1,2,3,3,3-heptafluoropropane (HFA227). Suitable aerosol compositions include surfactant-free or substantially surfactant-free aerosol compositions. The aerosol composition may contain up to about 5% by weight, for example 0.002 to 5%, 0.01 to 3% by weight of the active ingredient, based on the weight of the propellant. The aerosol composition may also contain a co-solvent such as ethanol in an amount up to 30% by weight of the composition, particularly for administration from a pressurised metered dose inhalation device (See [0016]).
It is disclosed that in the aerosol composition where the active ingredient is present in particulate form, the active ingredient may have an average particle diameter of up to about 10 μm, preferably 1 to 5 μm (See [0018]).
Hassan et al teach that the said formulations may be surfactant free and ethanol may be present. Additionally, Ashurst et al expressly disclose that aerosol formulations may be free of all excipients including ethanol and surfactants.
Hassan et al lack a specific disclosure on the propellant being 1,1-difluroethane. This is known in the art as shown by Corr et al and Backstrom et al and evidenced by DAIKIN HFC-152a or UNFCCC (Global Warming Potentials).
Ashurst et al teach a metered dose inhaler for dispensing an inhalation drug formation comprising fluticasone propionate or a physiologically acceptable solvate thereof and a fluorocarbon propellant, optionally in combination with one or more other pharmacologically active agents or one or more excipients (See abstract).
Ashurst et al teach that the said drug formulations may be free or substantially free of formulation excipients e.g. surfactants and cosolvents etc. Such drug formulations are advantageous since they may be substantially taste and odour free, less irritant and less toxic than excipient-containing formulations. Thus, a preferred drug formulation consists essentially of albuterol or a physiologically acceptable salt thereof, optionally in combination with one or more other pharmacologically active agents, and a fluorocarbon propellant (See Col. 4, lines 6-18).
Ashurst et al exemplify formulations that include a suspension of albuterol (active agent) in a propellant (See examples 2-6).
Corr et al teach a pharmaceutical composition comprising a drug, 1 ,1-difluoroethane (R-152a) propellant and ethanol that is suitable for delivering the drug, especially from a pressurised aerosol container using a metered dose inhaler (MDI). The drug formulation will comprise a propellant, in which the drug is dissolved, suspended or dispersed, and may contain other materials such as co- solvents, surfactants and preservatives (See Page 1, lines 1-3 and 18-20).
Disclosed is a sealed container that contains the said pharmaceutical solution which is a pressurized aerosol container for use with a metered dose inhaler (MDI) (See claims 20-22).
Corr et al disclose that there is a need for a MDI aerosol formulation that has a reduced GWP in comparison with R-134a and R-227ea, that has acceptable flammability and toxicity performance and which forms stable suspensions or solutions with a range of pharmaceutical actives and with reduced irritancy (See page 3, line 33-34 to page 4, line 2).
Thus, Corr et al disclose the use of a propellant consisting essentially of and preferably consisting entirely of 1 ,1- difluoroethane (R-152a) in a pharmaceutical composition comprising a drug, the propellant and ethanol in order to reduce the amount of ethanol required for dissolving the drug in the pharmaceutical composition compared to the amount that would be needed if 1 ,1 ,1 ,2-tetrafluoroethane (R-134a) is used as the propellant (See page 4, lines 4-10).
It is disclosed that “By the term "consists essentially of” we mean that at least 90 weight %, preferably at least 95 weight %, more preferably at least 98 weight % and especially at least 99 weight % of the propellant component is 1 ,1-difluoroethane
(R-152a)” (See page 5, lines 13-18).
Corr et al, in a preferred embodiment, provide a pharmaceutical solution for a medication delivery apparatus, especially a metered dose inhaler, which consists essentially of: (a) a liquefied propellant component consisting essentially of and preferably consisting entirely of 1 ,1-difluoroethane (R-152a); (b) ethanol; and (c) a drug component dissolved in the propellant/ethanol mixture consisting of at least one drug selected from the group consisting of beclomethasone dipropionate (BDP) and fluticasone propionate (FP) (See page 7).
The said pharmaceutical solutions are for use in medicine for treating a patient suffering from a respiratory disorder and especially asthma or a chronic obstructive pulmonary disease. (See page 8, lines 1-10).
Corr et al further disclose that the FPF (fine particle fraction) of the emitted dose of the said formulation comprising HFA 152a and ethanol is 53.7% or 46.3% (See pages 15-16 and Tables 4-5).
Evidences:
DAIKIN HFC-152a product information discloses that HFC-152a has a lower global warming potential compared to other fluorocarbons. With its physical properties resembling those of HFC-134a, is used as an environment-friendly substitute for HFC-134a as aerosol propellant.
UNFCCC (Global Warming Potentials) provides a list of all gases with their global warming potential and atmospheric lifetime. The list shows that HFC-152a has an atmospheric lifetime of 1.5 years and a 20 years GWP of 460, while the same values are 14.6 and 3400 for HFC-134a and 36.5 and 4300 for HFC-227a.
It would have been obvious to a person of ordinary skilled in the art at the time the invention was made to have combined the teachings of Corr et al and Ashurst et al with that of Hassan et al and as evidenced by DAIKIN HFC-152a product information and/or UNFCCC (Global Warming Potentials) to arrive at the instant invention. It would have been obvious to do so because Hassan et al teach formulations comprising mometasone furoate and formoterol fumarate dihydrate and an HFA propellant, delivered by a metered dose inhaler for inhalation. Hassan et al disclose that the said formulations may be free of surfactants and ethanol. Ashurst et al also teach suspension formulations for use in a metered dose inhaler consisting essentially of one or more active agents in an HFA propellant Ashurst et al specifically disclose that preferred formulations are free of excipients. Neither reference disclose presence of water, acid stabilizers or perforated structures. Corr et al teach inhalation compositions or a metered dose inhaler comprising the said formulation comprising one or more drugs for inhalation, ethanol and a propellant. Corr et al disclose that 1,1-difluoroethane (HFA 152a) is a more suitable propellant than HFA-134 because it has lower GWP and is environmentally friendly choice for aerosolization of formulations. Corr et al also disclose that the propellant is consisting essentially of and preferably consisting entirely of 1,1- difluoroethane (R-152a). As such one of ordinary skill in the art having possession of the teachings of the references would have been motivated to have substituted HFA-152 for the HFA propellants of Hassan et al because it is highly recommended by Corr et al and also by DAIKIN HFC-152a product information and/or UNFCCC (Global Warming Potentials), with a reasonable expectation of success.
In other words, the claims would have been obvious because the technique for improving a particular formulation was part of the ordinary capabilities of a person of ordinary skill in the art, in view of the teaching of the technique for improvement in other situations.
While the references do not expressly disclose the level of impurity from degradation in storage, it is considered that the same formulations stored in the same device would have the same properties and characteristics.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP §§ 706.02(l)(1) - 706.02(l)(3) for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1, 3-8, 10, 12-14 and 21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 6-10 and 12 of U.S. Patent No. 10,258,568 in view of Mueller-Walz (US 20070256685) and Ashurst et al (6,532,955).
The obviousness Double Patenting rejection is appropriate because while the conflicting claims are not identical, they are not patentably distinct from the reference claims. The instant claims would have been obvious over the reference claims in view of Muller-Walz and Ashurst et al.
Examined claims are drawn to a composition comprising a mometasone compound, formoterol fumarate dihydrate, and a propellant comprising 1,1-difluoroethane (R-152a).
Reference claims are drawn to a pharmaceutical composition comprising: a) beclomethasone dipropionate (BDP) and/or fluticasone propionate (FP); b) propellant 1,1-difluoroethane (R-152a); and c) a first amount of ethanol.
Specifically, the differences are that the examined claims require mometasone and formoterol fumarate dihydrate, while the reference claims require beclomethasone dipropionate and/or fluticasone. However, it would have been obvious to one of ordinary skill in the art to have selected different active agents for the same formulations as taught by Mueller–Walz which teach inhalable suspension formulations comprising a propellant such as HFA-152 and wherein the active agent may be mometasone furoate, formoterol fumarate di-hydrate, beclomethasone dipropionate, fluticasone propionate, etc. As such one of ordinary skill in the art would have been more than motivated to have selected any active agent or combinations thereof for their known benefits and excepted effectiveness. The factual underpinning is that different active agents are considered alternatively usable species and as such one of ordinary skill in the art is more than capable of substituting one species / active agent for another with a reasonable expectation of success.
Additionally, Ashurst et al teach that preferred formulations are free of excipients including ethanol and surfactants. Thus, one of ordinary skill in the art would have been motivated to have excluded ethanol from the reference claims to reduce undesired effects of excipients.
In this regard, the courts have held that “It is generally considered to be prima facie obvious to substitute components which are taught by the prior art to be well known and useful for the same purpose in order to form a composition that is to be used for an identical purpose. The motivation for substituting them flows from their having been used in the prior art, and from their being recognized in the prior art as useful for the same purpose. As shown by the recited teachings, instant claims are no more than the substituting conventional components of pharmaceutical active agents, and particularly steroids. It therefore follows that the instant claims define prima facie obvious subject matter. Cf. In re Ruff, 256 F.2d 590, 118 USPQ 340 (CCPA 1958).
Claims 1, 3-8, 10, 12-14 and 21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8, 10-13 of U.S. Patent No. 10,258,569 in view of Mueller-Walz (US 20070256685) and Ashurst et al (6,532,955).
The obviousness Double Patenting rejection is appropriate because while the conflicting claims are not identical, they are not patentably distinct from the reference claims. The instant claims would have been obvious over the reference claims in view of Mueller-Walz and Ashurst et al.
Examined claims are drawn to a composition comprising a mometasone compound, formoterol fumarate dihydrate, and a propellant comprising 1,1-difluoroethane (R-152a).
Reference claims are drawn to a pharmaceutical solution comprising: a) a liquefied propellant comprising 1,1-difluoroethane (R-152a); b) 1-20 wt% of ethanol, and c) beclomethasone dipropionate (BDP) and fluticasone propionate (FP).
Specifically, the differences are that the examined claims require mometasone, while the reference claims require beclomethasone dipropionate and/or fluticasone. However, it would have been obvious to one of ordinary skill in the art to have selected different active agents for the same formulations as taught by Mueller–Walz which teach inhalable suspension formulations comprising a propellant such as HFA-152 and wherein the active agent may be mometasone furoate, formoterol fumarate dihydrate, beclomethsone dipropionate, fluticasone propionate, etc. As such one of ordinary skill in the art would have been more than motivated to have selected any active agent or combinations thereof for their known benefits and excepted effectiveness. The factual underpinning is that different active agents are considered alternatively usable species and as such one of ordinary skill in the art is more than capable of substituting one species / active agent for another with a reasonable expectation of success.
Additionally, Ashurst et al teach that preferred formulations are free of excipients including ethanol and surfactants. Thus, one of ordinary skill in the art would have been motivated to have excluded ethanol from the reference claims to reduce undesired effects of excipients.
In this regard, the courts have held that “It is generally considered to be prima facie obvious to substitute components which are taught by the prior art to be well known and useful for the same purpose in order to form a composition that is to be used for an identical purpose. The motivation for substituting them flows from their having been used in the prior art, and from their being recognized in the prior art as useful for the same purpose. As shown by the recited teachings, instant claims are no more than the substituting conventional components of pharmaceutical active agents, and particularly steroids. It therefore follows that the instant claims define prima facie obvious subject matter. Cf. In re Ruff, 256 F.2d 590, 118 USPQ 340 (CCPA 1958).
Claims 1, 3-8, 10, 12-14 and 21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 10-19 and 21 of U.S. Patent No. 10,668,018 in view of Mueller-Walz (US 20070256685) and Ashurst et al (6,532,955).
The obviousness Double Patenting rejection is appropriate because while the conflicting claims are not identical, they are not patentably distinct from the reference claims. The instant claims would have been obvious over the reference claims in view of Mueller-Walz and Ashurst et al.
Examined claims are drawn to a composition comprising a mometasone compound, formoterol fumarate dihydrate, and a propellant comprising 1,1-difluoroethane (R-152a).
Reference claims are drawn to a composition comprising at least one corticosteroid; a propellant comprising R-152a and first amount of ethanol and a second amount of ethanol, wherein the composition is a solution.
Specifically, the differences are that the examined claims require mometasone and formoterol fumarate dihydrate while the reference claims require a drug comprising at least one corticosteroid. This is however obvious in view of Mueller-Walz which teach inhalable suspension formulations comprising a propellant and wherein the active agent may be a corticosteroid such as mometasone furoate, formoterol fumarate dihydrate, beclomethasone, etc, and mixtures thereof. As such one of ordinary skill in the art would have been more than motivated to have selected any active agent or combinations thereof for their known benefits and excepted effectiveness. The factual underpinning is that different active agents are considered alternatively usable species and as such one of ordinary skill in the art is more than capable of substituting one species / active agent for another with a reasonable expectation of success.
Additionally, Ashurst et al teach that preferred formulations are free of excipients including ethanol and surfactants. Thus, one of ordinary skill in the art would have been motivated to have excluded ethanol from the reference claims to reduce undesired effects of excipients.
In this regard, the courts have held that “It is generally considered to be prima facie obvious to substitute components which are taught by the prior art to be well known and useful for the same purpose in order to form a composition that is to be used for an identical purpose. The motivation for substituting them flows from their having been used in the prior art, and from their being recognized in the prior art as useful for the same purpose. As shown by the recited teachings, instant claims are no more than the substituting conventional components of pharmaceutical active agents, and particularly steroids. It therefore follows that the instant claims define prima facie obvious subject matter. Cf. In re Ruff, 256 F.2d 590, 118 USPQ 340 (CCPA 1958).
Claims 1, 3-8, 10, 12-14 and 21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 7-9, 11-16, 29-31, 34-40 of U.S. Patent No. 10,792,256 in view of Finch et al (US 20140248357), Mueller-Walz (US 20070256685) and Ashurst et al (6,532,955).
The obviousness Double Patenting rejection is appropriate because while the conflicting claims are not identical, they are not patentably distinct from the reference claims. The instant claims would have been obvious over the reference claims in view of Finch et al, Mueller-Walz and Ashurst et al.
Examined claims are drawn to a composition comprising a mometasone compound, formoterol fumarate dihydrate, and a propellant comprising 1,1-difluoroethane (R-152a).
Reference claims are drawn to a composition comprising at least one salmeterol compound, optionally at least on long acting muscarinic antagonist, at least one corticosteroid and a propellant comprising of R-152a and ethanol.
Specifically, the difference is that the examined claims require mometasone while the reference claims require at least one salmeterol compound, optionally at least one LAMA and at least one corticosteroid. The modifications in the type and number of active agents in the formulation, however, would have been obvious to one of ordinary skill in the art in view of Finch et al and Mueller-Walz which teach inhalable formulations comprising HFA 152a and wherein the active agent may be a corticosteroid such as mometasone furoate, fluticasone and other active agents such as salmeterol, formoterol fumarate dihydrate, etc, and mixtures thereof. As such one of ordinary skill in the art would have been more than motivated to have selected any active agent or combinations thereof for their known benefits and excepted effectiveness. The factual underpinning is that different active agents are considered alternatively usable species and as such one of ordinary skill in the art is more than capable of substituting one species / active agent for another with a reasonable expectation of success.
Additionally, Ashurst et al teach that preferred formulations are free of excipients including ethanol and surfactants. Thus, one of ordinary skill in the art would have been motivated to have excluded ethanol from the reference claims to reduce undesired effects of excipients.
In this regard, the courts have held that “It is generally considered to be prima facie obvious to substitute components which are taught by the prior art to be well known and useful for the same purpose in order to form a composition that is to be used for an identical purpose. The motivation for substituting them flows from their having been used in the prior art, and from their being recognized in the prior art as useful for the same purpose. As shown by the recited teachings, instant claims are no more than the substituting conventional components of pharmaceutical active agents, and particularly steroids. It therefore follows that the instant claims define prima facie obvious subject matter. Cf. In re Ruff, 256 F.2d 590, 118 USPQ 340 (CCPA 1958).
Claims 1, 3-8, 10, 12-14 and 21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims of U.S. Patent No. 11,690,823; 11,179,366; 11,642,330; 11,077,076; 11,311,502; 11,103,480; 11,260,052; 11,559,507; 11,559,505; 10,792,256; 10,888,546 in view of Finch et al (US 20140248357), Mueller-Walz (US 20070256685) and/or Keller et al (6,585,958) and Ashurst et al (6,532,955).
The obviousness Double Patenting rejection is appropriate because while the conflicting claims are not identical, they are not patentably distinct from the reference claims. The instant claims would have been obvious over the reference claims in view of Finch et al, Mueller-Walz and Ashurst et al.
Examined claims are drawn to a composition comprising a mometasone compound, formoterol fumarate dihydrate, and a propellant comprising 1,1-difluoroethane (R-152a).
Reference claims are drawn to a composition comprising at least one active agent, propellant R-152a and ethanol.
Specifically, the difference is that the reference claims require mometasone and formoterol or any solvate thereof, while examined claims require other active agents. This however is obvious in view of Finch et al and Mueller-Walz, as stated above.
Also as taught by Keller et al, the disclosed active agents are alternatively usable species in compositions treating respiratory diseases and specially in inhalation formulations.
Furthermore, Keller et al disclose that alternatively usable propellants include HFA 134, HFA 227, HFA 152a, etc.
The factual underpinning is that different active agents are considered alternatively usable species and as such one of ordinary skill in the art is more than capable of substituting one species / active agent for another with a reasonable expectation of success.
Additionally, Ashurst et al teach that preferred formulations are free of excipients including ethanol and surfactants. Thus, one of ordinary skill in the art would have been motivated to have excluded ethanol from the reference claims to reduce undesired effects of excipients.
In this regard, the courts have held that “It is generally considered to be prima facie obvious to substitute components which are taught by the prior art to be well known and useful for the same purpose in order to form a composition that is to be used for an identical purpose. The motivation for substituting them flows from their having been used in the prior art, and from their being recognized in the prior art as useful for the same purpose. As shown by the recited teachings, instant claims are no more than the substituting conventional components of pharmaceutical active agents, and particularly steroids. It therefore follows that the instant claims define prima facie obvious subject matter. Cf. In re Ruff, 256 F.2d 590, 118 USPQ 340 (CCPA 1958).
As the number of patents applied under obviousness type double patenting is very large, they are rejected collectively and based on similar analysis as stated above.
Claims 1, 3-8, 10, 12-14 and 21 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 and 21-23 of copending Application No. 17/944,637 (US 20230029180) as evidenced by Mueller-Walz (US 20070256685) and Ashurst et al (6,532,955).
The obviousness Double Patenting rejection is appropriate because while the conflicting claims are not identical, they are not patentably distinct from the reference claims. The instant claims would have been obvious over the reference claims in view of Mueller-Walz and Ashurst et al.
Examined claims are drawn to a composition comprising a mometasone compound, formoterol fumarate dihydrate, and a propellant comprising 1,1-difluoroethane (R-152a).
Reference claims are drawn to a pharmaceutical composition comprising at least one mometasone compound, ethanol and a propellant component comprising 1,1-difluoroethane (R-152a).
Specifically, the difference is in that the drug component in the examined claims is a combination of mometasone and formoterol, while the reference claims recite mometasone alone. the arrangement of the limitations. This however would have been obvious to one of ordinary skill in the art as both drug components are known to be incorporated in formulations individually and in combination as evidenced by the references of record including Mueller-Walz. As such one of ordinary skill in the art would have been more than motivated to have selected the claimed drug components or combinations thereof for their known benefits and excepted effectiveness. The factual underpinning is that different active agents are considered alternatively usable species and as such one of ordinary skill in the art is more than capable of substituting one species / active agent for another with a reasonable expectation of success.
Additionally, Ashurst et al teach that preferred formulations are free of excipients including ethanol and surfactants. Thus, one of ordinary skill in the art would have been motivated to have excluded ethanol from the reference claims to reduce undesired effects of excipients.
In this regard, the courts have held that “It is generally considered to be prima facie obvious to substitute components which are taught by the prior art to be well known and useful for the same purpose in order to form a composition that is to be used for an identical purpose. The motivation for substituting them flows from their having been used in the prior art, and from their being recognized in the prior art as useful for the same purpose. As shown by the recited teachings, instant claims are no more than the substituting conventional components of pharmaceutical active agents, and particularly steroids. It therefore follows that the instant claims define prima facie obvious subject matter. Cf. In re Ruff, 256 F.2d 590, 118 USPQ 340 (CCPA 1958).
This is a provisional nonstatutory double patenting rejection.
Claims 1, 3-8, 10, 12-14 and 21 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5, 8-12 and 15-24 of copending Application No. 17/969,250 (US 20230051849).
The obviousness Double Patenting rejection is appropriate because while the conflicting claims are not identical, they are not patentably distinct from the reference claims. The instant claims would have been obvious over the reference claims.
Examined claims are drawn to a composition comprising a mometasone compound, formoterol fumarate dihydrate, and a propellant comprising 1,1-difluoroethane (R-152a).
Reference claims are drawn to a composition comprising a drug component consisting of mometasone and formoterol, ethanol and a propellant comprising R-152a.
Specifically, the difference is in the arrangement of the limitations. The other difference is that examined claims recite that the formulation is in suspension form while the reference claims do not. However, reference claims are not restricted to any dosage form and encompass suspensions. The factual underpinning is that different active agents are considered alternatively usable species and as such one of ordinary skill in the art is more than capable of substituting one species / active agent for another with a reasonable expectation of success.
In this regard, the courts have held that “It is generally considered to be prima facie obvious to substitute components which are taught by the prior art to be well known and useful for the same purpose in order to form a composition that is to be used for an identical purpose. The motivation for substituting them flows from their having been used in the prior art, and from their being recognized in the prior art as useful for the same purpose. As shown by the recited teachings, instant claims are no more than the substituting conventional components of pharmaceutical active agents, and particularly steroids. It therefore follows that the instant claims define prima facie obvious subject matter. Cf. In re Ruff, 256 F.2d 590, 118 USPQ 340 (CCPA 1958).
Claims 1, 3-8, 10, 12-14 and 21 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 6-18, 20, 22-26 of copending Application No. 17/460,585 (US 20210386717) in view of Mueller-Walz (US 20070256685) and Ashurst et al (6,532,955).
The obviousness Double Patenting rejection is appropriate because while the conflicting claims are not identical, they are not patentably distinct from the reference claims. The instant claims would have been obvious over the reference claims in view of Mueller-Walz and Ashurst et al.
Examined claims are drawn to a composition comprising a mometasone compound, formoterol fumarate dihydrate, and a propellant comprising 1,1-difluoroethane (R-152a).
Reference claims are drawn to a composition comprising a drug component comprising tiotropium bromide monohydrate and a propellant comprising R-152a. Depending claims add other active agents including formoterol and mometasone.
Specifically, the difference is in the arrangement of the limitations. The other difference is that main reference claims do not recite or exclude ethanol and surfactants, while a depending claim adds ethanol and another excludes it.
The differences however would have been obvious to one of ordinary skill in the art as all recited drug components are known to be incorporated in formulations individually and in combination as evidenced by the references of record including Mueller-Walz. As such one of ordinary skill in the art would have been more than motivated to have selected the claimed drug components or combinations thereof for their known benefits and excepted effectiveness. The factual underpinning is that different active agents are considered alternatively usable species and as such one of ordinary skill in the art is more than capable of substituting one species / active agent for another with a reasonable expectation of success.
Additionally, Ashurst et al teach that that the said formulations may contain excipients such as ethanol or not. Preferred formulations are free of excipients including ethanol and surfactants. Thus, one of ordinary skill in the art would have been motivated to have included or excluded ethanol from the reference claims to reduce undesired effects of excipients.
In this regard, the courts have held that “It is generally considered to be prima facie obvious to substitute components which are taught by the prior art to be well known and useful for the same purpose in order to form a composition that is to be used for an identical purpose. The motivation for substituting them flows from their having been used in the prior art, and from their being recognized in the prior art as useful for the same purpose. As shown by the recited teachings, instant claims are no more than the substituting conventional components of pharmaceutical active agents, and particularly steroids. It therefore follows that the instant claims define prima facie obvious subject matter. Cf. In re Ruff, 256 F.2d 590, 118 USPQ 340 (CCPA 1958).
Claims 1, 3-8, 10, 12-14 and 21 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4, 7-9, 13-16, 20, 22-23, 26, 39 and 41 of copending Application No. 16/334,156 (US 20190388436) in view of Keller et al (6,585,958) and Ashurst et al (6,532,955).
The obviousness Double Patenting rejection is appropriate because while the conflicting claims are not identical, they are not patentably distinct from the reference claims. The instant claims would have been obvious over the reference claims in view of Keller et al and Ashurst et al.
Examined claims are drawn to a composition comprising a mometasone compound, formoterol fumarate dihydrate, and a propellant comprising 1,1-difluoroethane (R-152a).
Reference claims are drawn to a composition comprising a drug component comprising beclomethasone dipropionate and formoterol fumarate dihydrate, a propellant comprising R-152a and glycerol. Depending claims add other active agents including ipratropium or tiotropium.
Specifically, the difference is in the arrangement of the limitations. The other difference is that main reference claims do not recite or exclude ethanol and surfactants, while a depending claim excludes the surfactant.
The differences however would have been obvious to one of ordinary skill in the art as all recited drug components are known to be incorporated in formulations individually and in combination as evidenced by the references of record including Keller et al. The factual underpinning is that different active agents are considered alternatively usable species and as such one of ordinary skill in the art is more than capable of substituting one species / active agent for another with a reasonable expectation of success. Also as taught by Keller et al, the disclosed active agents are alternatively usable species in compositions treating respiratory diseases and specially in inhalation formulations.
Keller et al also disclose an aerosol formulation comprising a solvent including ethanol and glycerol. Thus, based on the teachings of the art including Keller et al, ethanol and glycerol are also alternatively usable species for the same or similar formulations.
Furthermore, Keller et al disclose that alternatively usable propellants include HFA 134, HFA 227, HFA 152a, etc.
Additionally, Ashurst et al teach that that the said formulations may contain excipients such as ethanol or not. Preferred formulations are free of excipients including ethanol and surfactants. Thus, one of ordinary skill in the art would have been motivated to have included or excluded ethanol from the reference claims to reduce undesired effects of excipients.
In this regard, the courts have held that “It is generally considered to be prima facie obvious to substitute components which are taught by the prior art to be well known and useful for the same purpose in order to form a composition that is to be used for an identical purpose. The motivation for substituting them flows from their having been used in the prior art, and from their being recognized in the prior art as useful for the same purpose. As shown by the recited teachings, instant claims are no more than the substituting conventional components of pharmaceutical active agents, and particularly steroids. It therefore follows that the instant claims define prima facie obvious subject matter. Cf. In re Ruff, 256 F.2d 590, 118 USPQ 340 (CCPA 1958).
Claims 1, 3-8, 10, 12-14 and 21 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 25-41, 43-56 of copending Application No. 16/582,710 (US 20200016174) in view of Keller et al (6,585,958) and Ashurst et al (6,532,955).
The obviousness Double Patenting rejection is appropriate because while the conflicting claims are not identical, they are not patentably distinct from the reference claims. The instant claims would have been obvious over the reference claims in view of Keller et al and Ashurst et al.
Examined claims are drawn to a composition comprising a mometasone compound, formoterol fumarate dihydrate, and a propellant comprising 1,1-difluoroethane (R-152a).
Reference claims are drawn to a composition comprising a drug component comprising beclomethasone dipropionate and formoterol fumarate dihydrate, a propellant comprising R-152a and glycerol. Depending claims add other active agents including ipratropium or tiotropium.
Specifically, the difference is in the arrangement of the limitations. The other difference is that main reference claims do not recite or exclude ethanol and surfactants, while a depending claim excludes the surfactant.
The differences however would have been obvious to one of ordinary skill in the art as all recited drug components are known to be incorporated in formulations individually and in combination as evidenced by the references of record including Keller et al. The factual underpinning is that different active agents are considered alternatively usable species and as such one of ordinary skill in the art is more than capable of substituting one species / active agent for another with a reasonable expectation of success. Also as taught by Keller et al, the disclosed active agents are alternatively usable species in compositions treating respiratory diseases and specially in inhalation formulations.
The factual underpinning is that different active agents are considered alternatively usable species and as such one of ordinary skill in the art is more than capable of substituting one species / active agent for another with a reasonable expectation of success. Also as taught by Keller et al, the disclosed active agents are alternatively usable species in compositions treating respiratory diseases and specially in inhalation formulations.
Furthermore, Keller et al disclose that alternatively usable propellants include HFA 134, HFA 227, HFA 152a, etc.
Additionally, Ashurst et al teach that that the said formulations may contain excipients such as ethanol or not. Preferred formulations are free of excipients including ethanol and surfactants. Thus, one of ordinary skill in the art would have been motivated to have included or excluded ethanol from the reference claims to reduce undesired effects of excipients.
In this regard, the courts have held that “It is generally considered to be prima facie obvious to substitute components which are taught by the prior art to be well known and useful for the same purpose in order to form a composition that is to be used for an identical purpose. The motivation for substituting them flows from their having been used in the prior art, and from their being recognized in the prior art as useful for the same purpose. As shown by the recited teachings, instant claims are no more than the substituting conventional components of pharmaceutical active agents, and particularly steroids. It therefore follows that the instant claims define prima facie obvious subject matter. Cf. In re Ruff, 256 F.2d 590, 118 USPQ 340 (CCPA 1958).
Claims 1, 3-8, 10, 12-14 and 21 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 28, 30-42 and 44 of copending Application No. 16/582,964 (US 20200016175) in view of Keller et al (6,585,958) and Ashurst et al (6,532,955).
The obviousness Double Patenting rejection is appropriate because while the conflicting claims are not identical, they are not patentably distinct from the reference claims. The instant claims would have been obvious over the reference claims in view of Keller et al and Ashurst et al.
Examined claims are drawn to a composition comprising a mometasone compound, formoterol fumarate dihydrate, and a propellant comprising 1,1-difluoroethane (R-152a).
Reference claims are drawn to a method of improving the chemical stability of a pharmaceutical composition, the composition comprising propellant R-152a, beclomethasone and formoterol fumarate dihydrate and wherein the composition is in the form of suspension.
Specifically, the differences are that the examined claims are drawn to a chemically stable composition while the reference claims are drawn to a method of improving the chemical stability of the composition, the active agents are different and the reference claims do not recite or exclude ethanol, surfactant or acid stabilizers. The differences would have been obvious to one of ordinary skill in the art in view of the teachings of Keller et al and Ashurst et al. regarding the preamble, it is noted that the said method of reference claims results in the chemically stable compositions of the examined application. The method claims do not add any critical step of limitation that distinguishes the method from the composition.
The factual underpinning is that different active agents are considered alternatively usable species and as such one of ordinary skill in the art is more than capable of substituting one species / active agent for another with a reasonable expectation of success. Also as taught by Keller et al, the disclosed active agents are alternatively usable species in compositions treating respiratory diseases and specially in inhalation formulations.
Furthermore, Keller et al disclose that alternatively usable propellants include HFA 134, HFA 227, HFA 152a, etc.
Additionally, Ashurst et al teach that that the said formulations may contain excipients such as ethanol or not. Preferred formulations are free of excipients including ethanol and surfactants. Thus, one of ordinary skill in the art would have been motivated to have included or excluded ethanol from the reference claims to reduce undesired effects of excipients.
In this regard, the courts have held that “It is generally considered to be prima facie obvious to substitute components which are taught by the prior art to be well known and useful for the same purpose in order to form a composition that is to be used for an identical purpose. The motivation for substituting them flows from their having been used in the prior art, and from their being recognized in the prior art as useful for the same purpose. As shown by the recited teachings, instant claims are no more than the substituting conventional components of pharmaceutical active agents, and particularly steroids. It therefore follows that the instant claims define prima facie obvious subject matter. Cf. In re Ruff, 256 F.2d 590, 118 USPQ 340 (CCPA 1958).
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Osborn et al (6,432,415).
Osborn et al teach bioadhesive formulations to deliver, for both local and systemic effects, a wide variety of drugs of varying degrees of solubility. These formulations can be gels or aerosols and comprise a solvent system comprising a volatile solvent and water, a solubilizing agent or a dispersing agent, or a mixture thereof, and a pharmaceutical (See abstract).
It is disclosed that there is an unexpected increase in solubility of Propellant 152a which is particularly advantageous for aerosol formulations comprising Propellant 152a because this reduces the need for using high amounts of ethanol to dissolve the Propellant (See Col.8, lines 56-67 and col. 9, lines 1-10).
In one aspect, the propellant is 1,1-difluoroethane also known as Propellant 152a, commercially available under the trade mark DymelRTM (See Col. 6, lines 27-34).
Pharmaceutical active agents include steroidal anti-inflammatory agents, adrenergics, etc, (See Col. 12, line 32 to Col. 13, line 10).
Keller et al (6,585,958).
Keller et al teach a pressure-liquefied propellant mixture for aerosols, comprising HFA propellants which can overcome problems with respect to suspension and solution aerosols and thus improved medicinal aerosol formulations can be obtained.
Keller et al disclose aerosol formulations that may comprise one or more of the active agents including beclomethasone, mometasone, fluticasone, formoterol, salbutamol, tiotropium bromide, etc.
The propellants include HFA-134, HFA 227 and HFA 152a. Suitable cosolvents include ethanol and glycerol.
Finch et al (US 20140248357).
Finch et al teach a composition for treatment of inflammatory respiratory disease by inhalation comprising a glitazone enantiomer (See abstract and [0018]). The said compositions may be used in combination with other drugs that are used in the treatment or suppression of the diseases or conditions for which present compounds are useful (See [0046]). Suitable therapeutic agents include beclomethasone dipropionate, fluticasone propionate, formoterol fumarate, mometsaone furoate, etc, (See [0047] and [0050]).
Finch et al also disclose that for delivery by inhalation, the active compound is preferably in the form of microparticles. These may be prepared by a variety of techniques, including micronisation. Hence the average particle size is denoted as equivalent d50. For inhaled use a d50 of less than 10 microns, preferably less than 5 microns is desired (See [0053]).
Finch et al state that the said composition may be prepared as a suspension for delivery from an aerosol in a liquid propellant, for example for use in a pressurised metered dose inhaler (PMDI). Propellants suitable for use in a PMDI are known to the skilled person, and include HFA-134a, HFA-227 (See [0054]).
The compositions may be dosed as described depending on the inhaler system used. In addition to the active compounds, the administration forms may additionally contain excipients, such as, surface-active substances, preservatives, flavorings, fillers, etc, (See [0058]).
Mueller-Walz (US 20070256685).
Mueller-Walz teach a pharmaceutical aerosol formulation comprising formoterol fumarate di-hydrate in suspension, and a steroid in suspension, and a propellant, ethanol, and optionally a surfactant, wherein the formoterol fumarate di-hydrate has a water content of about 4.8 to 4.28% by weight (See abstract). Mueller-Walz teach a pharmaceutical aerosol suspension formulation for use in a metered dose inhaler (MDI) comprising formoterol fumarate di-hydrate in suspension, and optionally a steroid in suspension, a propellant and ethanol, wherein the formoterol fumarate di-hydrate is provided as suspended particles and wherein the formulation is capable of being dispensed from an MDI to provide a Delivered dose of formoterol fumarate di-hydrate that has a variance of no more than +/-25%, of the mean Delivered dose when the formulation is stored at, 25 ºC and 60% rh, more particularly 40 ºC and 75% rh for up to 6 months. The said particles that are capable of penetrating the deep lung, e.g. having a diameter of less than about 5.8, more preferably less than about 4.7 microns. The said Delivered dose of formoterol fumarate di-hydrate with a fine particle fraction is from about 30 to 70% (See [0014]-[0016]).
Steroids may be selected from the group consisting of budesonide, mometasone, fluticasone, beclomethasone, mometasone furoate, etc (See [0033] and claim 7).
Suitable propellants for use in metered-dose aerosols include 1,1,2,2-tetrafluoroethane (HFA 134), difluoroethane (HFA 152a), 1,1,1,2,3,3,3-heptafluoropropane (HFA 227) and the like (See [0040] and claim 32).
Ethanol is employed in the said formulations in anhydrous form. And is present in amounts of less than 2.5% by weight to about 1% by weight, e.g. 1 to 1.5% by weight, more particularly 1 to about 1.45% by weight (See [0045]).
The said aerosol formulations can contain no, or substantially no surfactant, i.e. contain less than approximately 0.0001% by weight of surface-active agents. The said formulations can contain surface-active agents such as oleic acid, lecithin, etc, (See [0047]).
A valve can then be crimped onto the vial, and a pre-mix of propellant and ethanol can be introduced through the valve under pressure. The vials may be filled with sufficient formulation to provide a plurality of dosages. The vials or canisters used to contain the said formulations may be of plastics, metal or glass construction (See [0050]-[0052]).
It is disclosed that the said formulations find use as medicinal aerosol preparations for the treatment of disease states of the lung, for example asthma, COPD, etc, (See [0054]).
Backstrom et al (6,932,962).
Backstrom et al teach hydrofluoroalkane (HFA) propellants for example 1,1,1,2-tetrafluoroethane (P134a), 1,1,1,2,3,3,3-heptafluoropropane (P227) and 1,1-difluoroethane (P152a) are today considered to be the most promising new propellants. Not only are they environmentally acceptable, but they also have low toxicity and vapor pressures suitable for use in aerosols (See col. 1, lines 40-46 and col. 2, lines 39-42).
Disclosed is a pharmaceutical aerosol formulation wherein the formulation comprises a propellant selected from the group consisting of 1,1,1,2-tetrafluoroethane (P134a), 1,1,1,2,3,3,3-heptafluoropropane (P227), or 1,1-difluoroethane (P152a). Also disclosed and claimed is a metered dose inhaler comprising the formulation comprising 1,1-difluoroethane (P152a) (See claims 4 and 40).
The said formulations for inhalation may also comprise a surfactant selected from a C8 -C16 fatty acid or salt thereof, a bile salt, a phospholipid or an alkyl saccharide. In addition to medicament, propellant and surfactant, a small amount of ethanol (normally up to 5% but possibly up to 20%, by weight) may be included in the said formulations (See col. 2, lines 3-15 and 47-54).
Suitable medicaments for the said formulations include mometasone and formoterol or a salt thereof (See col. 2, lines 54-67 and claims 12, 29 and 48). One disclosed salt of formoterol is fumarate (See Example 1).
The active agents can be micronized and in a suspension form. Micronised active agents mixed with excipients and propellants are added to a plastic coated glass bottle and sealed with a metering valve (See at least Examples, 1-4 and claims 1 and 37-39).
Response to Arguments
Applicant's arguments filed 12/15/25 have been fully considered but they are not persuasive.
Applicant’s amendments to the claims have necessitated modified grounds of rejections. Applicant’s arguments so far as they pertain to the maintained references and rejections are discussed below.
Applicant’s first argument is regarding the rejection of claims over Hassan et al, in combination with Corr et al. Applicant’s main argument is that the combination of references does not teach the claims as amended. Specifically, the claims have been amended to exclude ethanol recite that water is preset at less than 100 ppm. Applicant argues that while Hassan et al teach that ethanol may be present that the formulations comprise ethanol. Applicant points to Hassan et al’s Example 1, which comprises ethanol (See Remarks, pages 6-8).
The above arguments are neither persuasive nor applicable to the current rejection. Firstly, it is noted that the references are not required to disclose examples of every composition they teach for them to meet the claimed composition. That is, it is well-established that “consideration of a reference is not limited to the preferred embodiments or working examples, but extends to the entire disclosure for what it fairly teaches, when viewed in light of the submitted knowledge in the art, to a person of ordinary skill in the art’. In re Boe, 355, F.2d 961, 148 USPQ 510, 510 (CCPA 1966).
Secondly, the rejection now relies on the teachings of Ashurst et al which clearly teach that the same formulation may comprise ethanol or preferably does not. Ashurst et al encourage one of ordinary skill in the art to prepare the said suspension formulations without excipients including ethanol and surfactants because the formulations would have less irritating and toxic.
Applicant also argues against the combination of references of Hassan et al and Corr et al as evidenced by DAIKIN HFC-152a product information and/or UNFCCC and states that Corr et al teach different active agents than Hassan et al do and that Corr et al teach solutions and not suspensions and Hassan et al teach. Applicant argues that one of ordinary skill in the art would not be motivated to have combined the teachings of Corr et al and Hassan et al.
The above arguments are not persuasive. Regarding the different active agents, it is noted that as the preponderance of evidence shows, it is clearly obvious to substitute one active agent for another in the same dosage form. Additionally, Corr ‘711 also teach that “There is a need for a MDI aerosol formulation that has a reduced GWP in comparison with R-134a and R-227ea, that has acceptable flammability and toxicity performance and which forms stable suspensions or solutions with a range of pharmaceutical actives and with reduced irritancy”.
Furthermore, while Corr et al teach solution formulations comprising different active agents, the reference is relied upon for its teaching and suggestion on selecting HFA-152a propellant and one of ordinary skill in the art would clearly be motivated to substitute Hassan et al’s HFA propellant with HFA-152 per Corr et al’s disclosure and as evidenced by DAIKIN HFC-152a product information and/or UNFCCC both of which provide added motivation to one of ordinary skill in the art to select a better propellant such as HFA 152a. Thus, it would have been obvious to one of ordinary skill in the art that substituting HFA 152 of Corr et al for Hassan et al’s suspension formulations comprising mometasone and formoterol would lead to success.
Corr et al ‘711 specifically discloses that the HFA 227 and HFA 134 result in environmental issues and that “they are unlikely to be acceptable for use in the MDI sector for many years, if at all’.
Applicant further argues that Corr et al discloses solution formulations and no suspension formulations and that suspension is only mentioned in the background section (See Remarks, pages 9-10).
This argument is similarly unpersuasive. The references of record show that one of ordinary skill in the art is more than capable of making a solution or suspension of the same components/ formulations. For example, Hassan et al teach an admixture of one or more active agents including mometasone and formoterol and an HFA in solution or dispersion (See entire document including [0015]). Keller et al teach that the same formulations may be in the form of a solution or suspension. Sequeira et al (5,837,699) teach -aerosolized particles of mometasone furoate in the form of dry powder, solutions or suspensions-. Muller-Walz, clearly teach making a suspension formulation comprising one or two active agents including formoterol furoate and mometasone. Backstrom et al teach the same formulations comprising any of the HFAs including HFA 227, HFA 334 or HFA 152a can be in a suspension. It is further noted that instant Specification discloses that the same formulations may be in the form of a suspension or solution (See [0055], [0094] and [0104] of P.G. Publication).
Corr et al is relied upon for teaching, suggesting and motivating one of ordinary skill in the art to substitute R-152a for other commonly used HFA propellants and disclose its advantages to other HFAs including their lower impact on the environment. They are not relied upon for the specific formulation. Corr et al disclose that both solutions and suspensions can be made but disclose solutions of active agents with R-152a. There is no teaching in Corr et al that propellant R- 152a is not suitable for suspensions or only works in solution formulations. That is, in order to teach away, the prior art reference must “criticize, discredit, or otherwise discourage” the claimed invention. In re Fulton, 391 F.3d 1195, 1201 (Fed. Cir. 2004). This is not the case here.
Thus, the preponderance of evidence shows that Applicant’s arguments regarding unobviouness of making a suspension formulation comprising HFA 152a from the teachings of the references cannot be persuasive.
Next, Applicant’s point to unexpected results. Applicant argues that they have unexpectedly discovered that the combination of HFA 152a with mometasone and formoterol improves the stability of the composition compared to HFA 134a or 227 (See Remarks, pages 11-12).
This argument has been fully considered and found unconvincing. The Specification discloses that HFA152a compared to HFA 134a and 227 provides for a more chemical stability in the formulations. The Specification states:
It has been found that the use of propellants comprising 1,1-difluoroethane (R-152a) in pharmaceutical compositions containing a mometasone compound, such as mometasone furoate, either alone or together with a formoterol compound, such as formoterol fumarate dihydrate, can unexpectedly improve the chemical stability of the mometasone and formoterol compounds compared to the stability they exhibit in known formulations containing either R-134a or R-227ea as the propellant. (See [0069] and [0090] of the published Spec).
Similarly, Hassan et al teach a suspension composition comprising mometasone and formoterol fumarate dihydrate and that it has effectively been used to treat respiratory conditions such as asthma. Hassan et al do not point to a chemical stability problem with the combination. Additionally, Corr et al ‘711 teach that HFA 152a provides an improved chemical stability to formulations in suspension or solution. Specifically, Corr et al disclose:
the propellant should be of low acute and chronic toxicity and have a high cardiac sensitisation threshold. It should have a high degree of chemical stability in contact with the drug, the container and the metallic and non-metallic components of the MDI device, and have a low propensity to extract low molecular weight substances from any elastomeric or other polymeric materials in the MDI device. (See Corr et al 711, Page 1, 2nd para).
There is a need for a MDI aerosol formulation that has a reduced GWP in comparison with R-134a and R-227ea, that has acceptable flammability and toxicity performance and which forms stable suspensions or solutions with a range of pharmaceutical actives and with reduced irritancy. (See Corr et al 711, Pages 3-4)
Thus, one of ordinary skill in the art is more than motivated to substitute Hassan et al’s HFA propellant with Corr et al’s HFA 152a for its multiple disclosed benefits including better for environment and improved stability of the formulation. That is, from the disclosures, one of ordinary skill in the art would have expected improved chemical stability.
Additionally, evidence of unexpected results must be weighed against evidence supporting prima facie obviousness in making a final determination of the obviousness of the claimed invention. In re May, 574 F.2d 1082, 197 USPQ 601 (CCPA 1978). Looking at the prior art, it is known in the art that the combination of HFA152a with mometasone and formoterol fumarate dihydrate would have resulted in a chemically stable composition, thus one with ordinary skill would expect that with the substitution of HFA 152a for other HFAs, the chemical stability of the formulation would be improved. “Expected beneficial results are evidence of obviousness of a claimed invention, just as unexpected results are evidence of unobviousness thereof." In re Gershon, 372 F.2d 535, 538, 152 USPQ 602, 604 (CCPA 1967).
Furthermore, the above arguments are not found convincing because the rejections are based on the statue of obviousness. According to MPEP:
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
That is, obviousness comes from the references when the differences in one reference is obvious to one of ordinary skill in the art. Contrary to Applicant’s interpretation, the one of ordinary skill in the art would have been motivated to have combined the teachings as stated in the rejections. It is also noted that if one reference taught every limitation of the claims, it would normally be considered as anticipating the claims.
Applicant appears to assign a very narrow skill set to one skilled in the art. In response to applicant’s argument that one of ordinary skill in the art would not have been motivated to substitute HFA 152 for HFA 134 or 227, MPEP states that “the obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). As indicated in the rejection supra, it would have been prima facie obvious to a person of ordinary skilled in the art at the time the invention was made to have substituted HFA 152, a propellant that is less damaging to the environment for HFA 134 or 227, which are known to have some negative impact on the ozone and environment.
Regarding an ordinary artisan MPEP 2141 states that ““A person of ordinary skill in the art is also a person of ordinary creativity, not an automaton.” KSR, 550 U.S. at 421, 82 USPQ2d at 1397. “[I]n many cases a person of ordinary skill will be able to fit the teachings of multiple patents together like pieces of a puzzle.” Id. at 420, 82 USPQ2d at 1397. Office personnel may also take into account “the inferences and creative steps that a person of ordinary skill in the art would employ.” Id. at 418, 82 USPQ2d at 1396; and 2) MPEP 716.07: “It is to be presumed also that skilled workers would as a matter of course, if they do not immediately obtain desired results, make certain experiments and adaptations, within the skill of the competent worker.”
With regards to the rejection of claims on the ground of nonstatutory double patenting over claims of various reference patents or Applications, in view of Mueller-Walz (US 20070256685), Keller et al or Finch et al, Applicant argues either the solution / suspension difference or different active agents. Applicant requests a withdrawal of these rejections (See Remarks, pages 16-24).
The argument is not sufficient because the rejection clearly stated that the said differences between solution and suspension or different the active agents are rendered obvious by the secondary reference. For example, Mueller-Walz, teaches a composition comprising different active agents, and that it is would have been obvious to substitute one active agent for another in the same composition with a reasonable expectation of success. Thus, the factual underpinning is that different active agents are considered alternatively usable species and as such one of ordinary skill in the art is more than capable of substituting one species / active agent for another with a reasonable expectation of success.
In this regard, the courts have held that “It is generally considered to be prima facie obvious to substitute components which are taught by the prior art to be well known and useful for the same purpose in order to form a composition that is to be used for an identical purpose. The motivation for substituting them flows from their having been used in the prior art, and from their being recognized in the prior art as useful for the same purpose. As shown by the recited teachings, instant claims are no more than the substituting conventional components of pharmaceutical active agents, and particularly steroids. It therefore follows that the instant claims define prima facie obvious subject matter. Cf. In re Ruff, 256 F.2d 590, 118 USPQ 340 (CCPA 1958).
Regarding the argument of suspension not being obvious over solution, the argument is not found persuasive because as shown above, many of the references teach that the same formulation can effectively be in the form of a suspension or solution.
Applicant made analogous arguments regarding U.S. Patent No. 10,258,569, U.S. Patent No. 10,668,018, U.S. Patent No. 10,792,256, U.S. Patent No. 11,690,823; 11,179,366; 11,642,330; 11,077,076; 11,311,502; 11,103,480 and 11,260,052 in view of Finch and/or Mueller-Walz (See remarks, page 30).
The arguments are not found persuasive for the same reasons as stated above.
Regarding the rejection of claims under obviousness type double patenting over co-pending Application No. 16/334,156, 16/582,710, 16/582,964, 17/944,637 and 17/969,250 Applicant either made analogous arguments, which are not persuasive or made no argument and state that a Terminal Disclaimer will be submitted (See Remarks, pages 31-33).
Claims 1, 3-8, 10, 12-14 and 21 are rejected.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Mina Haghighatian whose telephone number is (571)272-0615. The examiner can normally be reached on M-F, 7-5 EST.
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/Mina Haghighatian/