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 .
Claims 1, 6, 9-10, 13-19, 21-28 and 31-33 have been presented for examination on the merits.
Priority
This application is a continuation of Application No. 17/861,072 which claims benefit of provisional Application No. 63/220,362 filed on 07/09/2021 and 63/282,356 filed on 11/23/2021.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 26 and 28 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method of treating asthma and COPD in a patient by administration of a composition according to claim 1 via a metered dose inhaler, does not reasonably provide enablement for a method of treating a pulmonary disease or disorder. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
To be enabling, the specification of a patent must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation. In Genentech Inc. v. Novo Nordisk 108 F.3d 1361, 1365, 42 USPQ2d 1001, 1004 (Fed. Cir. 1997); In re Wright 999 F.2d 1557, 1561, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993). See also Amgen Inc. v. Chugai Pharm. Co., 927 F.2d 1200, 1212, 18 USPQ2d 1016, 1026 (Fed. Cir. 1991); In re Fisher 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970) and In re Wands 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988).
There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is “undue”. See In re Wands, 858 F.2d 731, 737, 8 USPQ 2d 1400, 1404 (Fed. Cir. 1998). The court set forth the eight factors to consider when assessing if a disclosure would require undue experimentation. Citing Ex parte Forman, 230 USPQ 546, the court recited eight factors.
These factors include, but are not limited to:
1) The breadth of the claims,
2) The nature of the invention,
3) The state of the prior art,
4) The level of one of ordinary skill,
5) The level of predictability in the art,
6) The amount of direction provided by the inventor,
7) The existence of working examples,
8) The quantity of experimentation needed to male or use the invention based on the content of the disclosure.
(1 and 2) The breadth of the claims and the nature of the invention: The claims are broad. The claims are drawn to a method of treating a pulmonary disease or a disorder in a patient by administering by inhalation composition according to claim 1 (which includes propellant, glycopyrrolate, formoterol, budesonide and a phospholipid).
(3 and 5) The state of the prior art and the level of predictability in the art: The art teaches methods of treating disorders such as COPD and asthma by inhalation of active agents including glycopyrrolate, formoterol and budesonide. It is known in the art that the said active agents are not suitable for treating ALL pulmonary diseases and disorders such as lung cancer, cystic fibrosis, respiratory infections, etc. Accordingly, the level of predictability of "all" diseases and disorders being treatable with the said method, in the art is very low.
(6 and 7) The amount of direction provided by the inventors and the existence of working examples: Applicants have provided in the specification disclosure regarding treating COPD and asthma by inhalation of a composition comprising glycopyrrolate, formoterol and budesonide. In fact, these are the only two disorders that are named in the specification. In view of the various different disorders known (and not yet known) which may or may not be treatable with the claimed combination, further testing would be necessary to use the invention as broadly as claimed.
(8) The quantity of experimentation needed to make or use the invention bases on the content of the disclosure: The quantity of experimentation needed to make and use the invention based on the contents of the disclosure and the unpredictability asserted by the Applicant, is very high and not enabled by the specification.
Conclusion
For the forgoing reasons, the specification is not enabling for the scope of the claims.
In view of the unpredictability in the art, the lack of working examples, the excessive breadth of the claims and lack of guidance in the specification, it would require undue experimentation on the part of the person of skill in the art to practice the full scope of the invention.
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 6, 10 and 19 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 6 and 10 are indefinite for reciting a concentration unit of mg/mL for the composition of claim 1. However, it is not clear what the basis for the said mL is since the formulation does not recite a liquid carrier.
Claim 19 is indefinite for reciting “according to any of claim 17”. This appears to be a typographical error and is interpreted as according to claim 17.
Corrections are required.
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 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, 6, 9-10, 13-19, 21, 23-28 and 32-33 are rejected under 35 U.S.C. 103 as being unpatentable over Vehring et al (US 20190358150) in combination with Knopeck et al (US 20160324778), and as evidenced by Yang et al (Understanding Solvation in the Low Global Warming Hydrofluoroolefin HFO-1234ze Propellant).
Vehring et al teach compositions, methods and systems for pulmonary delivery of two or more active agents via a metered dose inhaler. The said two or more active agents are selected from long-acting muscarinic antagonist (“LAMA”), long-acting β2 adrenergic agonist (“LABA”), and corticosteroid active agents (See abstract and [0041]).
Regarding claim 1, Vehring et al teach that the active agent to be delivered by a suspension MDI (metered dose inhaler) is typically provided as a fine particulate dispersed within a propellant or combination of two or more propellants (i.e., a propellant “system”). In order to form the fine particulates, the active agent is typically micronized (See [0006] and [0150]). The active agent particles are provided as a micronized material wherein at least 90% of the active agent particles by volume exhibit an optical diameter of about 7 μm or less (See [0093]).
One exemplified formulation comprises formoterol, glycopyrrolate and budesonide (See Table 7).
The said compositions include a LABA active agent in combination with a LAMA active agent or a corticosteroid active agent. The agents include formoterol, glycopyrrolate and budesonide and any pharmaceutically acceptable salts, esters, isomers or solvates thereof. Vehring et al state that the suspending particles suitable for use in the said compositions include phospholipids and are perforated microstructures (See details below).
Regarding claim 6, Vehring et al teach that the amount of glycopyrrolate included in the compositions may be between about 0.04 mg/ml and about 2.25 mg/ml, the amount of formoterol in the compositions may be between about 0.01 mg/ml and about 1 mg/ml and budesonide is present at about 5.6 mg/ml (See [0098], [0105], [0110], [0217], claims 63, 66-67).
Regarding claim 9, Vehring et al teach that the suspending particles suitable for use in the said compositions include phospholipids. Exemplary phospholipids disteroylphosphatidylcholine, diphosphatidyl glycerol, etc. In one exemplary embodiment, the suspending particles comprise perforated microstructures. In a particular embodiment, perforated microstructures may include DSPC (1,2-Distearoyl-sn-Glycero-3-Phosphocholine) (See [0124], [0127] and [0192]). The said suspending particles also comprise a calcium salt, such as calcium chloride (See [0063], [0064], [0123]-[0125] and [0174]).
Regarding claim 10 and 19, Vehring et al teach an embodiment wherein a dispersion containing 2.8 g of DSPC and 0.26 g of calcium chloride in 400 mL of hot water was mixed. This results in a concentration of 7 mg/mL DSPC (See [0215]). While Vehring et al do not expressly disclose the delivered dose of phospholipid, this limitation is met by the disclosed concentration (i.e. 7 mg/mL).
Regarding claims 13-14 and 32, Vehring et al teach glycopyrrolate or any pharmaceutically acceptable salts, esters, isomers or solvates thereof and preferably bromide is present in the compositions in sufficient amount to provide a delivered dose selected from between about 10 μg and about 100 μg, or about 15 μg, from about 9 μg, 18 μg, etc, per actuation of the MDI. The glycopyrrolate is micronized and may be in a crystalline form (See [0093], [0108]-[0110]).
Regarding claims 15-16 and 33, Vehring et al teach that the formoterol is fumarate and is present at a concentration that achieves a delivered dose selected from between about 1 μg and about 10 μg, about 2 μg and 5 μg, about 2 μg and about 10 μg, up to about 10 μg, or up to about 5 μg per actuation of an MDI. Formoterol is micronized and may be in a crystalline form (See [0093], [0103]-[0105]).
Regarding claims 17-18, Vehring et al teach that the said compositions may include budesonide or any pharmaceutically acceptable salts, esters, isomers or solvates thereof, in an amount sufficient to provide target delivered dose selected from between about 30 μg and about 240 μg, about 30 μg and about 120 μg, or up to about 50 μg per actuation of an MDI. Budesonide is micronized (See [0093] and [0115]).
Regarding claim 21, Vehring et al disclose that in the said methods, the co-suspension compositions may be used in an MDI (metered dose inhaler) system. MDIs are configured to deliver a specific amount of a medicament in aerosol form. The said MDI system includes a pressurized, liquid phase formulation-filled canister disposed in an actuator formed with a mouthpiece. Inside an exemplary cartridge is a metering valve (reading on outlet valve) including a metering chamber capable of holding a defined volume of the formulation, which is released into an expansion chamber at the distal end of the valve stem when actuated. The actuator retains the canister and may also include a port with an actuator nozzle for receiving the valve stem of the metering valve. When actuated, the specified volume of formulation travels to the expansion chamber, out the actuator nozzle and into a high-velocity spray that is drawn into the lungs of a patient (See [0150]-[0151]).
Regarding claims 23-24, Vehring et al disclose that that the filled MDIs were stored valve down at 25° C/60% RH with a foil overwrap. The delivered dose uniformity provided by the said compositions was substantially preserved, even after 12 months storage of such compositions at 5° C. or after 4.5 months at 25° C. and 60% relative humidity (RH) for samples stored inside aluminum foil pouches to minimize water ingress into the MDI canister. The aerosol performance of such compositions was also evaluated throughout unprotected storage conditions extending up to 12 months. The said compositions showed no noticeable degradation in the particle size distribution of GP and FF delivered from the MDIs after six months. The said compositions maintain as much as 80%, 90%, 95%, or more, of the original FPF or FPD performance, even after being subjected to accelerated degradation conditions (See [0082], [0178] and [0183]-[0184]).
Regarding claim 25, Vehring et al disclose that the dose of each active agent delivered throughout emptying of an MDI canister is not more than 30% greater than the mean delivered dose and is not less than 30% less than the mean delivered dose. Therefore, methods of achieving a desired DDU of two or more active agents delivered from an MDI are also provided. In such embodiments, the method may include achieving a DDU for each of the two or more active agents delivered from an MDI selected from, for example, a DDU of ±30%, or better, a DDU of ±25%, or better, a DDU of ±20%, or better throughout emptying of the MDI canister from which the co-suspension composition is delivered (See [0082] and [0156]).
Regarding claims 26-28, Vehring et al disclose that the said methods include methods for treating a pulmonary disease or disorder amenable to treatment by respiratory delivery of the said co-suspension composition, wherein the said diseases include asthma, chronic obstructive pulmonary disease (COPD), allergic rhinitis, sinusitis, etc, (See [0046] and [0157]). It is also disclosed that glycopyrrolate, formoterol fumarate and budesonide can be used to treat inflammatory or obstructive pulmonary diseases and disorders.
Vehring et al disclose that the administration of the co-suspension composition results in an improvement in FEV1 AUC0-12 of at least 80 ml when compared to the FEV1 AUC0-12 achieved by a composition delivering a single active agent (See [0030], [0034] and [0163]).
Vehring et al lack a disclosure on the claimed propellant (HFO-1234zeE). This would have been obvious in view of the teachings of Knopeck et al as evidenced by Yang et al.
Knopeck et al teach medicinal compositions, and devices, methods and systems which use same, comprising a propellant and at least one medicinally active compound, said propellant comprising at least one fluoroolefin (See Abstract).
Knopeck et al disclose that “Thus, applicants have recognized a need for compounds, compositions, systems, devices and methods for medicament delivery that at once provide relatively low ozone depletion potential and relatively low global warming potential. Moreover, applicants have recognized that any composition, including any propellant contained therein, must also possess properties which ensure the efficacy of the medicament, such as medicament stability, low- or no-toxicity, and compatibility with the other components of the medicament delivery system” (See [0012]).
Regarding the propellant in claim 1, Knopeck et al teach that the said fluoroolefin comprises tetrafluoropropene, more preferably 1,1,1,3-tetrafluoropropene (HFO-1234ze) and/or 1,1,1,2-tetrafluoropropene (HFO-1234yf). The term HFO-1234ze is used herein generically to refer to 1,1,1,3-tetrafluoropropene, independent of whether it is the cis- or trans-form. The terms “cisHFO-1234ze” and “transHFO-1234ze” are used herein to describe the cis- and trans-forms of 1,1,1,3-tetrafluoropropene respectively (See [0014] and claims 1, 14 and 20).
It is disclosed that the said propellants have the advantage of not contributing substantially to ozone depletion or global warming compared to hydrofluoroalkanes, which are commonly used (See [0016]).
It is disclosed that HFO-1234ze comprises a combination of transHFO-1234ze and cisHFO-1234ze, and more preferably from about 90% to about 99% trans on the basis of total HFO-1234ze, with the cis isomer comprising from about 1% to about 10% of the same basis. The said propellant compositions comprise a combination of cisHFO-1234ze and transHFO1234ze, preferably in a cis:trans weight ratio of from about 1:99 to about 10:99, more preferably from about 1:99 to about 5:95. It is disclosed that transHFO-1234ze may be preferred for use in certain systems because of its relatively low boiling point (−19° C.) (See [0036]-[0037]).
Regarding the medicaments of claim 1, Knopeck et al teach that exemplary medicaments may be selected from, budesonide, mometasone furoate, formoterol and an anticholinergic (See [0027]).
Regarding claims 26-27, Knopeck et al teach that particularly preferred medicinal agents for use in the said compositions include bronchodilators and anti-inflammatory steroids for use in the treatment of respiratory disorders, such as asthma and chronic obstructive pulmonary disorder (COPD), by inhalation therapy (See [0026] and claim 25).
Knopeck et al also disclose inhaler being a metered dose inhaler, having a valve and an actuator and that the said system may facilitate uniform dose delivery by MDIs, and allow for more concentrated dispersions. In such preferred embodiments, at least a substantial proportion of the medicinally active particles, and preferably a major proportion, have hollow and/or porous perforated microstructures that substantially reduce attractive forces, such as van der Waals forces (See [0025]).
As evidenced:
Yang et al teach that hydrofluoroolefins (HFOs), with zero ozone-depleting effect and very low global warming potential, are considered to be the next-generation high-pressure working fluids. They have industrial relevance in areas including refrigeration and medical aerosols. One major challenge expected in the replacement of existing working fluids with HFOs is the solubility and solvation of additives in such hydrophobic and oleophobic low dielectric semifluorinated solvents. The study of the solvation of chemistries that represent those additives by HFOs is, therefore, of great relevance.
Yang et al teach that they systematically investigate how the polarity and structure of fragments (the tail, t) that represent those additives affect their binding energy (Eb) with HFO-1234ze (1,1,1,3-tetrafluoropropene). We also compare and contrast those results with those for the working fluids that are most widely used in the industry, the hydrofluoroalkanes (HFAs) HFA-134a and HFA-227. Three main chemistries were investigated: alkanes, ethers, and esters. It was found that HFO-1234ze interacts quite favorably with ethers and esters, as indicated by their Eb st, while Eb st with alkanes was much lower. While ether and ester groups showed little difference in Eb st, the much lower self-interaction energy between ether tail−tail fragments (Eb tt) is expected to result in improved solubility/solvation of those groups in HFO-1234ze when compared with the more polar ester groups. The ratio Eb st/Eb tt is defined as the enhancement factor (Eenh) and is expected to be a better predictor of solubility/solvation of the tail fragments. Finally, the solvation behavior of HFO-1234ze was found to be similar to that of HFA-134a, thus suggesting similar considerations may apply for both propellants, when solvation properties are of a concern to the application (See abstract).
In Table 1, Yang et al disclose some relevant physicochemical properties of the fourth-generation propellant HFO-1234ze compared with the hydrofluoroalkanes HFA-134a and HFA227. It is stated that within this context, hydrofluoroolefins (HFOs) have emerged as the fourth-generation propellants. HFOs have no ODE and very low GWP. HFO-1234ze (1,1,1,3-tetrafluoropropene), one of the HFO candidates, has been shown to be nonflammable, to have low toxicity (similar to that of HFAs), and to possess physicochemical properties similar to HFAs. These characteristics are expected to somewhat facilitate the transition process from HFAs to HFOs (See page 10676, 1st col.).
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 combined the teachings of Knopeck et al as evidenced by Yang et al with that of Vehring et al to arrive at the instant invention. It would have been obvious to do so because Vehring et al teach compositions comprising a combination of active agents including glyopyrrolate bromide, formoterol fumarate and budesonide, in particulate form and a method for treating asthma and COPD to a subject in need of such treatment wherein the administration is via a metered dose inhaler comprising the said formulation and a non-CFC propellant. Vehring et al provide adequate guidance on the concentrations and uniformity and stability of the said formulation. Knopeck et al teach a method of treating respiratory disorders such as asthma and COPD by administration of compositions comprising HFO-1234ze and pharmaceutically active agents including corticosteroids, beta-agonists and anticholinergics, etc, such as budesonide and formoterol and adjuvants such as surfactants. Knopeck et al specifically teach that HFO-1234ze is a better propellant because, at least, it is advantageous in not contributing to ozone depletion and global warming. Yang et al teach that HFO propellants, and especially HFO-1234ze is a suitable alternative to HFA propellants because of at least, their lower impact on the environment.
As such one of ordinary skill in the art having possession of Vehring et al’s formulations would been motivated to have looked in art for other suitable propellants that are less damaging to the environment s taught by Knopek et al and evidenced by Yang et al.
In other words, in view of the teachings of Vehring et al, Knopeck et al and Yang et al, there would have been a reasonable expectation that a composition comprising HFO-1234ze and pharmaceutically active agents including corticosteroids such as budesonide and formoterol and an anticholinergic such as glycopyrrolate could be successfully prepared and used in a method for treating pulmonary diseases such as asthma.
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.
Claims 1, 6, 9-10, 13-19, 21-28 and 31-33 are rejected under 35 U.S.C. 103 as being unpatentable over Vehring et al (US 20190358150) in combination with Knopeck et al (US 20160324778), and as evidenced by Yang et al (Understanding Solvation in the Low Global Warming Hydrofluoroolefin HFO-1234ze Propellant), as applied to claims 1 and 21 above, and in further view of Bonelli et al (US 20150306026) and/or Lulla et al (US 20100275912).
Vehring et al, Knopeck et al and Yang et al’s teachings are delineated above and incorporated herein.
The combined references lack a specific disclosure on the gasket, bromobutyl material (claim 22) and addition of roflumilast (claim 31). These are well known in the art as taught by Bonelli et al and/or Lulla et a.
Bonelli et al teach a pharmaceutical composition, comprising glycopyrronium bromide, an HFA propellant (See abstract).
Regarding claim 22, the disclosure provides a pressurized metered dose inhaler (MDI) or other container suitable for aerosol delivery, comprising the said pharmaceutical composition (See [0013], [0018], claim 8). It is disclosed that said MDI comprises a container/canister which is closed with a metering valve for delivering a daily therapeutically effective dose of the active ingredient. Generally, the metering valve assembly comprises a ferrule having an aperture formed therein, a body moulding attached to the ferrule which houses the metering chamber, a stem consisting of a core and a core extension, an inner- and an outer-seal around the metering chamber, a spring around the core, and a gasket to prevent leakage of propellant through the valve. The gasket seal and the seals around the metering valve may comprise elastomeric material such as EPDM, chlorobutyl rubber, bromobutyl rubber, butyl rubber, etc. The medicament may be delivered from the filled canister via the metering valve to the mouth of a patient e.g. a mouthpiece actuator (See [0041]-[0042] and [0044]).
Regarding claim 31, Bonelli et al teach that the said formulations may comprise glycopyrronium bromide and other active agents including roflumilast, formoterol fumarate and budesonide (See [0034]).
Bonelli et al further disclose that “generally speaking, doses of active ingredient are in the range of about 0.5 μg to 1000 μg per actuation, e.g. about 1 to 100 μg/actuation, and sometimes about 5 to 50 μg/actuation. The skilled person in the field is familiar with how to determine the appropriate dosage for each individual pharmaceutically active ingredient” (See [0035]).
Lulla et al teach an aerosol device, i.e. a metered dose inhaler (MDI) (See
abstract and [0036]).
Regarding claims 21-22, Lulla et al teach that said MDI comprises component parts of the valve assembly which may further comprise a seat gasket positioned between the valve chamber and the sealing piece. The seat gasket preferably surrounds the valve stem and is capable of sealing an aperture provided in the valve stem. The valve assembly is particularly suitable for application to aerosol devices containing medicament to be delivered to a patient, for example in the form of MDI canisters. (See [0042]-[0043], [0067]-[0069] and claim 109).
It is further disclosed that the elastomeric materials used in the aerosol device may be at least one of butyl, chloroprene, EPDM, chlorobutyl, and bromobutyl elastomer (See [0096]).
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 combined the teachings of Bonelli et al and/or Lulla et al and Knopeck et al as evidenced by Yang et al with that of Vehring et al to arrive at the instant invention. The reasons for combining Knopeck as evidenced by Yang et al with that of Vehring et al is delineated above and incorporated herein. It further would have been obvious to one of ordinary skill in the art having possession of the combined references to have looked in the art for specifics of the inhaler device including Bonelli et al and/or Lulla et al because Vehring et al and Knopek et al teach delivering the said formulations with a suitable metered dose inhaler comprising a canister, actuator and a metering valve and one of ordinary skill in the art would have wanted to make sure that the said device is both suitable and leak proof. Bonelli et al teach that a leakage proof device comprises gaskets made of a suitable material including bromobutyl. Lulla et al also disclose that the said MDI comprises a seat gasket and a body including a neck. The elastomeric material taught by Lulla et al include bromobutyl. Additionally, Bonelli et al teach that the said composition may comprise multiple active agents effective in treating asthma and COPD including roflumilast.
From the combined teaching of the cited references, one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention, as a whole, would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made.
The claims would have been obvious because a person of ordinary skill has good reasons to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense.
As such one of ordinary skill in the art having possession of the combined teachings on the formulations and the aerosol device would been motivated to have looked in art for specifics of the device such as gaskets to provide for a safe, effective and stable delivery process.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Rocha et al (Hydrofluoroalkane-philicity: Excipient Screening for Pressurized Metered Dose Inhaler Formulations).
Rocha et al reviews suitable excipients for aerosolized pharmaceutical formulations. It is disclosed that “HFOs have no ozone depleting potential because their double bond confers sufficient instability to reduce their atmospheric lifetime. They also have an ultra low GWP (6 for HFO-1234ze compared to 3200 for HFA-227). Two HFO propellants are currently being produced in large scale: 1,3,3,3-tetrafluoropropene (HFO-1234ze(E)) and 2,3,3,3-tetrafluoropropene (HFO-1234yf). In a comparison between HFO-1234ze(E) and HFA-134a, both showed similar toxicity profiles, thus paving the way for the consideration of HFOs as medical aerosols. The ab initio calculations discussed above allow us to gain insight into the solvation of various chemical functionalities by HFOs, and thus gain a predictive understanding of the challenges that might occur during a transition to HFOs. In Table 1, the magnitude of Ebst for HFO-1234ze(E) is seen to be comparable to that for HFA-134a for all fragments except CH2. This happens in spite of the lower dipole moment of HFO-1234ze(E) (1.14D) compared to HFA-134a (2.12D), behavior attributed to the greater number of heavy atoms (dispersion forces) in HFO-1234ze(E). Similar solvating behavior of HFO-1234ze(E) and HFA-134a propellants can be seen as a good indicator of its potential to replace HFA in pMDIs. Based on the similarity of Eenh (Table 2), a predictor of the (enthalpic) ability of the functionalities to stabilize dispersions in the semi-fluorinated alkanes, the results suggest that dispersions in HFO-1234ze(E) with such chemistries may be just as capable of yielding viable formulations as those based on HFA-134a” (See page 149).
Claims 1, 6, 9-10, 13-19, 21-28 and 31-33 are rejected.
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 M-F, 7-5 EST.
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/Mina Haghighatian/
Mina Haghighatian
Primary Examiner
Art Unit 1616