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 .
Information Disclosure Statement
The IDS filed on 12/3/2025 has been considered. See the attached PTO 1449 form.
Status of Action/Claims
Receipt of Remarks/Amendments filed on 12/15/2025 is acknowledged. Claims 28, 30-42 and 44 are currently pending and presented for examination on the merits for patentability.
Rejection(s) not reiterated from the previous Office Action are hereby withdrawn. The following rejections are either reiterated or newly applied. They constitute the complete set of rejections presently being applied to the instant application.
Withdrawn Rejections/Objections
The rejections of claim 42 and 43 under 112(b) has been withdrawn due to appropriate claim amendments.
The objection of claim 28 has been withdrawn due to appropriate claim amendments.
New/Maintained Claim Rejection(s)
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, 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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 28, 30-40, 42 and 44 are rejected under 35 U.S.C. 103 as being unpatentable over Gaetano (WO 2007/121913 A2; Nov. 1, 2007) in view of Noakes (WO 2012/156711 A1; Nov. 22, 2012), Keller et al. (US 6,585,958 B1; Jul. 1, 2003) and Jager et al. (US 5,676,930; Oct. 14, 1997) as evidenced by Watson et al. (US 2010/0008997 A1; Jan. 14, 2010) and PubChem (PubChem, Compound Summary, Formoterol Fumarate).
Gaetano throughout the reference teaches pharmaceutical solution formulations for pressurized metered dose inhalers capable of providing two or more active drug substances to the lungs for prevention or treatment of broncho-pulmonary disease (Abstract; Field of the invention; Claim 1 and 14).
Gaetano teaches solution formulations wherein one of the active drug substance is a beta-2 agonist which is formoterol fumarate (claims 2-4). As evidenced by PubChem, Formoterol Fumarate is synonymous to Formoterol Fumarate dihydrate and both Formoterol Fumarate and Formoterol Fumarate dihydrate represent the same compound which includes the dihydrate salt. The medicament also comprises an inhaled corticosteroid which is beclomethasone dipropionate (claims 6-8). The active drug substances are dissolved in an HFA propellant and co-solvent (claims 1 and 14). The HFA propellant is preferably HFA 134a, HFA 227 or mixtures thereof (pg. 9, line 9-10). The cosolvent is ethanol and its amount comprised between 5% and 20% w/w. Gaetano teaches that the formulation also comprise anticholinergic atropine-like derivatives which include ipratropium bromide, oxitropium bromide, tiotropium bromide and glycopyrronium bromide (i.e. salt of glycopyrrolate) (claims 9-10). Gaetano does not include or require a surfactant in the formulation and therefore reads on the claimed limitations wherein the formulation is free of surfactants. Regarding the claimed limitations wherein the composition is free of acid stabilizers, Gaetano teaches that the formulation of the invention may further contain small amounts of a mineral acid (pg. 9, line 15-17) and that adding a pre-determined amount of a strong mineral acid is optional (pg. 10, line 20-28). Further, Gaetano in the claimed embodiments, which are exemplified embodiments, does not teach inclusion of acid stabilizers. Therefore, Gaetano teaches the formulation being free of acid stabilizers. Further, the formulation of Gaetano does not comprise perforated microstructures or polymers having amide and/or carboxylic acid ester repeating structural units.
Furthermore, as stated above, Gaetano teaches solution formulations for pressurized metered dose inhaler and the reference further states that the pressurized solution formulations are filled in a device, such as an aerosol inhaler (i.e., pressurized aerosol container) (Page 10, lines 20-22). The pressurized aerosol inhalers are necessarily sealed as they are well known in the art before the effective filing date of the instant invention. Further, Gaetano teaches the metered dose inhaler filled with the pressurized solution is used to deliver the active drug substances to the lungs upon actuation of the metered dose inhaler (see: summary of invention). This reads on the claimed limitation wherein the sealed and pressurized container is operatively coupled with a metered dose inhaler.
Gaetano does not teach that the propellant component is 1,1-difluoroethane (HFA-152a) or the amount of 1,1-difluoroethane in the propellant component as recited in instant claims. Gaetano also does not teach the composition is in the form of a suspension. However, these deficiencies are cured by Noakes.
Noakes teaches pharmaceutical metered dose inhaler fitted with a sealed and pressurized aerosol container comprising a propellant component consisting essentially of 1,1-difluoroethane, ethanol, and beclomethasone dipropionate and fluticasone propionate as the drug component (Abstract; Claims). The reference teaches that at least 99 weight % of the propellant component is 1,1-difluoroethane based on the total weight of the propellant component or the propellant component is entirely 1,1-difluoroethane (see Claims 4 and 5). Furthermore, the reference teaches that 1,1,1,2-tetrafluoroethane (i.e. HFA 134a) has high global warming potentials (GWP), 1430, and most pharmaceutical actives for treating respiratory disorders, such as asthma, tend not to dissolve well (see: Page 2, line 23-26 and Page 3, line 9-19). Noakes states that there is a need for a metered dose inhaler formulation that has a reduced GWP in comparison with HFA-134, has acceptable flammability and toxicity performance and which forms stable suspensions or solutions with a range of pharmaceutical actives with reduced irritancy (see: Page 3, line 33-34 and Page 4, line 1-2). The reference discloses that the pharmaceutical composition of the invention have global warming potential of, preferably, less than 250 (see Page 6, line 4-6) and that the composition consisting entirely of 1,1-difluoroethane as the propellant reduces the amount of ethanol required to dissolve the drug in the composition (see Page 4, line 12-19).
Gaetano does not expressly teach the drug component comprises from 0.01 to 2.5 weight% of the total weight of the composition. However, this deficiency is also addressed by Noakes.
Noakes teaches the metered dose inhaler formulation comprises the drug component in an amount which ranges from 0.01 to 2 weight % of the composition (Pg. 6, line 13-17).
The above references do not expressly teach the formulation comprising less than 500 ppm but greater than 0.5 ppm of water and the formulation comprising less than 1000 ppm but greater 0.5 ppm of dissolved oxygen. However, Gaetano does teach metering valves fitted with gaskets made of chloroprene-based rubbers can be used to reduce the ingress of moisture which can adversely affect the stability of the drug (page 11, line 2-7). These deficiencies are further addressed by Jager et al. and Keller et al. as evidenced by Watson et al.
Jagger teaches stabilized medicinal aerosol solution formulations comprising ipratropium bromide and 1,1,1,2-tetrafluoroethane(Abstract). It teaches other propellants that can be used include 1,1-difluoroethane (Col. 2, line 52-67). It also teaches formoterol as a medicament that can be included in the formulation (Col. 4, line 20-26). With regards to the amount of water in the formulation Jagger teaches that in propellant/cosolvent systems, the medicament may interact with the cosolvent and/or water present in the system to produce decomposition or degradation products (Col. 2, line 8-11). The reference further goes on to teach that small amounts of water may be added (up to about 5% by weight) to the propellant system to aid in manufacturing (Col. 3, line 13-20). This amount taught by Jagger overlaps with the instantly claimed amount of water. As evidenced by Watson, Naturally occurring levels of oxygen in water are typically no more than 10 ppm, which is considered to be a level of 100% dissolved oxygen (see: Para 0200 of Watson et al.). The presence of water of up to about 5% and dissolved oxygen in water of no more than 10 ppm overlap the amount of water and dissolved oxygen recited in the instant claims.
Further, the Keller reference teaches that with the aid of dinitrogen oxide it is possible to displace oxygen from the hydrofluoroalkanes (i.e. HFA 134a and HFA 152a), as a result of which the storage stability of oxidation-sensitive active compounds is improved (Col. 6, line 40-43).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Gaetano to incorporate the teachings of Noakes and substitute HFA 134a propellant with 1,1-difluoroethane. One would have been motivated to do so because, as discussed supra, Noakes teaches that 1,1-difluoroethane has lower global warming potential of 250 when compared to HFA 134a which has global warming potential of 1430. Moreover, Noakes teaches that high levels of ethanol can have unacceptable irritancy to the mouth and throat (see Page 3, line 28-31) and that the composition consisting entirely of 1,1-difluoroethane as the propellant reduces the amount of ethanol required to dissolve the drug in the composition and forms stable suspensions or solutions. Therefore, one of ordinary skill in the art would have been motivated to incorporate the propellant taught by Noakes into the teachings of Gaetano.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Gaetano to incorporate the teachings of Noakes and make the composition in the form of a suspension. One would have been motivated to do so because Noakes discusses problems related to HFA-134a propellant in solutions and suspensions and as discussed supra, Noakes teaches that incorporation of 1,1-difluoroethane as the propellant allows for a metered dose inhaler with low GWP in comparison with HFA-134a, reduced irritancy and forms stable suspensions or solutions. Noakes teachings suggest that it was well known in the art that metered dosed inhalers can be made in the form of solution and suspension and it further provides motivation of achieving stable solution and suspension with the use of 1,1-difluoroethane as the propellant and therefore it would have been obvious to one of ordinary skill in the art to make the formulation in the form of a suspension.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Gaetano to incorporate the teachings of Noakes and include the drug component in the amount taught by Noakes. One would have been motivated to do so because Gaetano teaches the active drug component in a metered dose inhaler for prevention or treatment of broncho-pulmonary disease, but is silent on the total amount of the active in the composition and it would have been obvious to one skilled in the art to look towards the teachings of Noakes for the total amount drug components to add in the composition since such amounts were known in the art as shown in Noakes. Further, one skilled in the art would have found it obvious to manipulate the amount of the drug based on factors such as severity of disease, size or weight of patient and determine an amount which would be optimal for the patient. Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the above references to incorporate the teachings of Jagger and Keller and include water in small amount. One would have been motivated to do so because the reference teaches that though water present in the system interacts with medicament to produce decomposition or degradation products, a small amount of water can be added to aid in manufacturing. One of ordinary skill in the art would have had a reasonable expectation of success of incorporating the teachings of Jagger because both Gaetano and Jagger teach an aerosol propellant formulation with similar medicaments and propellants. Further, as discussed supra and as evidenced by Watson, Naturally occurring levels of oxygen in water are typically no more than 10 ppm, which is considered to be a level of 100% dissolved oxygen. Thus, the presence of water would include dissolved oxygen in water of no more than 10 ppm. In addition, as discussed above, Keller teaches that displacing oxygen from the hydrofluoroalkanes results in improved storage stability of oxidation-sensitive active compounds but is silent on how much oxygen can be left since it would be difficult to keep the composition completely oxygen-free, which is also acknowledged in the instant specification (see Page 5, line 18-25). It would have been obvious to one skilled in the art to manipulate the amount of oxygen and determine an amount which would be optimal for the storage stability of oxidation-sensitive active compounds such formoterol taught by the combination of the prior art references above. Further, as discussed supra, Gaetano teaches metering valves fitted with gaskets made of chloroprene-based rubbers can be used to reduce the ingress of moisture which can adversely affect the stability of the drug (page 11, line 2-7). Therefore, one skilled in the art would have been strongly motivated to formulate the composition having very little amount of water content (such as the amount recited in instant claims) because Gaetano teaches that presence of moisture can adversely affect the stability of the drug.
With regards to instantly claimed limitation wherein the drug component comprises beclomethasone, formoterol, and long acting muscarinic antagonist, while the Gaetano reference does not exemplify this drug combination in the formulation, Gaetano teaches the formulation can comprise two or more active drug substances which include beclomethasone, formoterol and anticholinergic atropine-like derivatives such as ipratropium bromide, oxitropium bromide, tiotropium bromide and glycopyrronium bromide (i.e. salt of glycopyrrolate) (see Page 7, line 11-25). Therefore, all of the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions and the combination would have yielded predictable results to one of ordinary skill in the art at the time of the invention. Note: MPEP 2141 KSR International CO. v. Teleflex Inc. 82 USPQ 2d 1385 (Supreme Court 2007). Further, the Gaetano reference teaches that long-acting beta agonist such as formoterol and antimuscarinic agents in combination with inhaled corticosteroids have been proposed for the prevention and/or treatment of diseases (see Page 2, line 4-7). Therefore, it would have been obvious to one of ordinary skill in the art to include the disclosed long-acting muscarinic antagonist and formoterol with the beclomethasone agent in the formulation.
Regarding claims 38-39, the Noakes reference provides the motivation for incorporating HFA-152a because of its lower global warming potential and other advantages discussed above. The structure of the prior art method and composition is the same as the method and the composition recited in the instant claims. Therefore, the formulations comprising HFA-152a propellant along with other instantly claimed components would necessarily yield the same level of impurities.
Furthermore, Table 6 and 7 of the instant specification show that the percentage of total impurities for both HFA-134a and HFA-152a at 1 month and 3 months is less than the claimed amount of 1.5% and 2.0%. These comparative examples in the disclosure of the instant invention do not show any criticality between HFA-152a and HFA-134a with regards to the total impurities as claimed in claims 38 and 39 because both of these examples read on the claimed percentage of total impurities. Therefore, even when the formulations use the HFA-134a propellant as taught in Gaetano, because there is no unexpected results between HFA-134a and HFA-152a with regards to the impurities, both HFA-134a and HFA-152a would produce compositions with levels of impurities that fall within the scope of the instant claims.
Regarding claim 40, Noakes provides the motivation for adding the 1,1-difluoroethane (R-152a) propellant to the composition and therefore the composition comprising the claimed propellant (1,1-difluoroethane) would necessarily be stabilized compared to HFA-134a or HFA-227ea. Further, as discussed above, the Noakes reference teaches that R-152a propellant reduces the amount of ethanol required to dissolve the drug and provides stable solution and suspension.
With regards to the method of improving the stability of a pharmaceutical composition recited in the instant claims, as discussed supra, the references cited above teach the instantly claimed method of adding a propellant (i.e. 1,1-difluoroethane) to the pharmaceutical composition and this would necessarily result in improved stability of the pharmaceutical composition because the combination of the references cited teach the same method and composition as instantly claimed. Moreover, as discussed supra, Noakes states that there is a need for a metered dose inhaler formulation that has a reduced GWP in comparison with R-134 and R-227ea, has acceptable flammability and toxicity performance and which forms stable suspensions or solutions with a range of pharmaceutical actives with reduced irritancy and discloses the 1,1-difluoroethane propellant to fulfill these needs, which include stable suspensions or solutions.
With regards to the claimed limitation wherein the drug component is the sole drug component in the pharmaceutical composition as recited in claim 28, claim 28 also recites the drug component comprising and the comprising language does not exclude other ingredients in the claimed drug component. Also, dependent claims 30-33 recite including additional active ingredients (i.e., long acting muscarinic antagonist) in the drug component. In light of these recitations in the claims, the examiner interprets that the recitation “the drug component is the sole drug component in the pharmaceutical composition” means there is a sole drug component in the composition which comprises beclomethasone, formoterol and long acting muscarinic antagonists, and since the claim recites the drug component comprising, the comprising language does not exclude further ingredients in the drug component.
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.
Claim 41 is rejected under 35 U.S.C. 103 as being unpatentable over Gaetano (WO 2007/121913 A2; Nov. 1, 2007) in view of Noakes (WO 2012/156711 A1; Nov. 22, 2012), Keller et al. (US 6,585,958 B1; Jul. 1, 2003) and Jager et al. (US 5,676,930; Oct. 14, 1997) as evidenced by Watson et al. (US 2010/0008997 A1; Jan. 14, 2010) and PubChem (PubChem, Compound Summary, Formoterol Fumarate) as applied to claims 28, 30-40, 42 and 44 above and further in view of Malhotra et al. (US 2015/0250713 A1; Sep. 10, 2015).
The teachings of the above cited reference have been set forth above.
The above cited references do not teach the composition further comprises a surfactant. However, this deficiency is cured by Malhotra.
Malhotra also teach metered dose inhaler formulations for treating respiratory diseases wherein the formulations comprise the active drug and propellant component, including HFA-152a. (Abstract; Summary of Invention; Para 0051). Malhotra teaches that one or more surfactants may be employed to stabilize the composition and to also provide lubrication to the valve system of the metered dose inhaler (Para 0059).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to incorporate the teachings of Malhotra and further comprise a surfactant in the formulation of Gaetano. One would have been motivated to do so because Malhotra also teach metered dose inhaler formulations for treating respiratory diseases wherein the formulations comprise the active drug and propellant component, including HFA-152a and Malhotra provides the motivation that one or more surfactants may be employed to stabilize the composition and to also provide lubrication to the valve system of the metered dose inhaler.
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.
Response to Arguments
Applicant argued Gaetano teaches away from suspension form of its formulation because Gaetano teaches solution formulations offer the advantage of being homogenous with the active ingredient and solution formulations also obviate physical stability problems associated with suspension formulations so assuring more consistent uniform dosage administration. Thus, Gaetano discourages suspension form of the formulation taught by Gaetano. Applicant argued that each of Gaetano and Noakes does not disclose any examples of suspensions, and Noakes does not disclose any suspensions containing HFA-152a.
In response, while Gaetano teaches solution formulation of MDIs having certain advantages and exemplifies only solution formulation, Gaetano teaches that it is well known the formulations for aerosol administration via MDIs can be solutions or suspensions (e.g., pg. 1, line 18-19). As discussed supra, Noakes also teaches that MDI formulations can be in the form of either a suspension or a solution. Noakes teaches there is need for a MDI aerosol formulation that has reduced GWP in comparison with R-134 and R-227, that has acceptable flammability and toxicity performance and which forms stable suspensions or solutions with a range of pharmaceutical actives and with reduced irritancy and Noakes in the very next paragraph teaches the use of HFA-152a which would provide the reduced GWP and stable suspensions or solutions (page 3-4 of Noakes). While the examples disclosed in Noakes are MDIs in solution form, the examiner respectfully draws applicant’s attention to MPEP 2123 which states “Disclosed examples and preferred embodiments do not constitute a teaching away from the broader disclosure or non-preferred embodiment.” In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971). MPEP 2123. Therefore, while Noakes focuses on solution formulations, Noakes clearly teaches that MDI formulations can be in the form of a solution or suspension. Further, Noakes makes statements about solution formulations wherein Noakes discloses that pharmaceutical actives tend not to dissolve well in either R-134a or R-227ea and have to be handled as suspensions in the propellant. The problem of poorly dissolving drugs has been addressed by including a carrier solvent in the composition in which the drug is soluble, such as ethanol, and/or by adding a surfactant to the composition to produce a more stable suspension. However, neither of these solutions is ideal. (see page 3 of Noakes). Thus, the combination of Gaetano and Noakes suggests that both solution and suspension formulations have drawbacks with 134a and 227ea propellants and Noakes teaches using HFA-152a to address the problems disclosed in Noakes. Therefore, absence any unexpected results, it would have been obvious to one skilled in the art to make a suspension or solution formulation because both Gaetano and Noakes teach that solution and suspension formulations in MDIs are well known in the art and thus, one would have a reasonable expectation of success. Further, regarding the argument that Gaetano teaches solution formulations obviate physical stability problems associated with suspension formulations so assuring more consistent uniform dosage administration, Noakes teaches the use of HFA-152a which would provide reduced GWP and stable suspensions or solutions. Therefore, use of HFA-152a to provide stable suspension would obviate stability problems associated with suspension formulations so assuring more consistent uniform dosage administration. Thus, use of suspension formulation does not appear to go against the principal teachings of Gaetano.
Applicant argued that Gaetano does not teach any specific water amount as recited in the amended claims.
In response, applicant’s attention is respectfully drawn to the new 103 rejection in view of Keller, Jagger and Watson, which render obvious to specific amounts of the water and dissolved oxygen recited in the amended claims. Further, although the reference does not disclose all the characteristics and properties (e.g. water content) of the composition disclosed in the present claims, based on the substantially identical process using identical components, the Examiner has a reasonable basis to believe that the properties claimed in the present invention are necessarily present in the composition disclosed in the prior art. Because the PTO has no means to conduct analytical experiments, the burden of proof is shifted to the Applicant to prove that the properties are not necessarily present. ““[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art' s functioning, does not render the old composition patentably new to the discoverer.” Atlas Powder Co. v. Ireco Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus the claiming of a new use, new function or unknown property which is necessarily present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977).” MPEP § 2112, I.
Applicant reiterated the argument that the claimed formulation of beclomethasone and formoterol exhibit superior chemical stability when blended together with HFA-152a rather than HFA-134a.
In response, as discussed supra, Noakes discusses problems related to HFA-134a propellant in solutions and suspensions and as discussed supra, Noakes teaches that incorporation of 1,1-difluoroethane as the propellant allows for a metered dose inhaler with low GWP in comparison with HFA-134a, reduced irritancy and forms stable suspensions or solutions. Noakes suggests that the claimed HFA-152a propellant provide chemical stability to the composition with the active drug and the propellant (HFA-152a) would be capable of providing a stable suspension and solution. (see: page 1, lines 21-34; page 3, line 32 to page 4, line 10). Thus, appellant’s argument that the claimed propellant (HFA-152a) providing chemical stability is unexpected is not persuasive because the prior art already suggests the claimed HFA-152a propellant providing stable compositions. Therefore, the examiner concludes that the appellant have not shown that the claimed compositions are surprisingly and unexpectedly stable over what the prior art teaches.
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 § 2146 et seq. 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 28, 30-42 and 44 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 25-57 of copending Application No. 16/582,710 (USPGPUB No. 20200016174) in view of Malhotra et al. (US 2015/0250713 A1; Sep. 10, 2015).
The ‘710 application recites a pharmaceutical composition comprising beclomethasone dipropionate and formoterol fumarate dehydrate as the drug component and 1,1- difluoroethane as the propellant component. The chemically stable pharmaceutical composition is within a sealed and pressurized container that is operatively coupled with a metered dose inhaler. The drug component comprises from 0.01 to 2.5 weight%. The composition is in the form of suspension. ‘710 recites the composition contains less 500 ppm of water and also oxygen in the amount instantly claimed. ‘710 recite the drug component additionally comprises long-acting muscarinic antagonists including tiotropium and glycopyrronium bromide which the salt of glycopyrrolate. ‘710 recite that at least 90, 95 and 99 weight % of the propellant component is 1,1-difluoroethane which read on instant claims. ‘710 recites propellant component contains from 0.5 to 10 ppm of unsaturated impurities. ‘710 recites the composition is free of surfactants and perforated microstructures which read on instant claims. ‘710 recite the weight of total impurities which read on instant claims. ‘710 recite the composition in the form of suspension. ‘710 recites the composition is free of acid stabilizers.
Regarding claim 40, ‘710 application teaches the 1,1-difluoroethan (R-152a) propellant added to the composition and therefore it would necessarily be stabilized compared to HFA-134a or HFA-227ea.
The ‘710 application does not teach the composition further comprises a surfactant. However, this deficiency is cured by Malhotra.
Malhotra also teach metered dose inhaler formulations for treating respiratory diseases wherein the formulations comprise the active drug and propellant component, including HFA-152a. (Abstract; Summary of Invention; Para 0051). Malhotra teaches that one or more surfactants may be employed to stabilize the composition and to also provide lubrication to the valve system of the metered dose inhaler (Para 0059).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to incorporate the teachings of Malhotra and further comprise a surfactant in the formulation of ‘710. One would have been motivated to do so because Malhotra also teach metered dose inhaler formulations for treating respiratory diseases wherein the formulations comprise the active drug and propellant component, including HFA-152a and Malhotra provides the motivation that one or more surfactants may be employed to stabilize the composition and to also provide lubrication to the valve system of the metered dose inhaler.
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.
Even though the claims in the instant invention are directed towards a method and ‘710 application is directed towards a composition, the instant claims still read on ‘710 application claims because the instant claims recite the same composition.
This is a provisional nonstatutory double patenting rejection.
Claims 28, 30-42 and 44 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 4, 7-9, 13-16, 20, 22-23, 26 and 39-40 of copending Application No. 16/334,156 (USPGPUB No. 20190388436) in view of Malhotra et al. (US 2015/0250713 A1; Sep. 10, 2015).
The ‘156 application in claim 1 recites a pharmaceutical composition comprising glycerol, beclomethasone dipropionate and formoterol fumarate dihydrate as the drug component and 1,1- difluoroethane as the propellant component. ‘156 recite amounts of water and oxygen which read on instant claims. Claims 7-9 of ‘156 recite the drug component additionally comprises long acting muscarinic antagonists including tiotropium and salt of glycopyrrolate. Claims 13 and 14 of ‘156 recite weight % of the propellant component that reads on instant claims. Claim 15 of ‘156 recites propellant component contains 0.5 to 10 ppm of unsaturated impurities which reads on instant claims. Claims 20 and 26 of ‘156 recite the composition is free of surfactants, perforated microstructures and acid stabilizers which read on instant claims. Claims 22 and 23 recite the weight of total impurities which read on instant claims. Claims 24 and 25 of ‘156 recite the composition in the form of suspension and solution which reads on instant claims.
Regarding claim 20 and 40, ‘156 application teaches the 1,1-difluoroethane (R-152a) propellant added to the composition and therefore it would necessarily be stabilized compared to HFA-134a or HFA-227ea.
The ‘156 application does not teach the composition further comprises a surfactant. However, this deficiency is cured by Malhotra.
Malhotra also teach metered dose inhaler formulations for treating respiratory diseases wherein the formulations comprise the active drug and propellant component, including HFA-152a. (Abstract; Summary of Invention; Para 0051). Malhotra teaches that one or more surfactants may be employed to stabilize the composition and to also provide lubrication to the valve system of the metered dose inhaler (Para 0059).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to incorporate the teachings of Malhotra and further comprise a surfactant in the formulation of ‘156. One would have been motivated to do so because Malhotra also teach metered dose inhaler formulations for treating respiratory diseases wherein the formulations comprise the active drug and propellant component, including HFA-152a and Malhotra provides the motivation that one or more surfactants may be employed to stabilize the composition and to also provide lubrication to the valve system of the metered dose inhaler.
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.
Even though the claims in the instant invention are directed towards a method and ‘156 application is directed towards a composition, the instant claims still read on ‘156 application claims because the instant claims recite the same composition.
This is a provisional nonstatutory double patenting rejection.
Claims 28, 30-42 and 44 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4-18, 20, 22-30 of copending Application No. 17/460,585 (USPGPUB No. 20210386717) in view of Gaetano (WO 2007/121913 A2; Nov. 1, 2007).
The ‘585 application claims a pharmaceutical composition comprising a propellant component at least 90 weight % of which is 1,1-difluoroethane, a drug component comprising tiotropium bromide and the composition is free of acid stabilizers. The composition is in the form of suspension. The composition is within a sealed and pressurized container that is operatively coupled with a metered dose inhaler (claim 1, 13, 22, 24, 25, 26). ‘585 claims the composition further comprises formoterol fumarate dihydrate or beclomethasone dipropionate along with tiotropium (claims 6-9). ‘585 claims the composition comprising water and oxygen in the amount recited in instant claims. ‘585 claims the weight percent of the propellant component (claim 10, 11, 24) in the amount that reads on instant claims. ‘585 recites propellant contains 0.5 to 10 ppm of unsaturated impurities (claims 12 and 14). ‘585 recites the composition is free of perforated microstructures and other components (claim 15). ‘585 also teach the composition in a metered dose inhaler. (claims 1, 13, 22, 24, 25, 26).
While ‘585 teaches the composition comprises formoterol fumarate dihydrate or beclomethasone dipropionate along with tiotropium, ‘585 does not teach wherein the composition comprising glycopyrrolate and specifically glycopyrronium bromide. However, this deficiency is cured by Gaetano.
As discussed supra, Gaetano teaches the composition can comprise anticholinergic atropine-like derivatives which include ipratropium bromide, oxitropium bromide, tiotropium bromide and glycopyrronium bromide (i.e. salt of glycopyrrolate) (see Page 7, line 11-25). Further, the reference teaches that long acting beta agonist such as formoterol and antimuscarinic agents in combination with inhaled corticosteroids have been proposed for the prevention and/or treatment of diseases (see Page 2, line 4-7). Therefore, it would have been obvious to one of ordinary skill in the art to comprise the salt of glycopyrrolate in the formulation because the combination of the different drugs was known to be beneficial in preventing or treating disease. Further, it would have been obvious to one of ordinary skill in the art to try and substitute one antimuscarinic agent already taught by ‘585 application for another as a person with ordinary skill has good reason to pursue known options within his or her technical grasp. see MPEP 2141 KSR International CO. v. Teleflex Inc. 82 USPQ 2d 1385 (Supreme Court 2007).
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.
Even though the claims in the instant invention are directed towards a method and ‘585 application is directed towards a composition, the instant claims still read on ‘585 application claims because the instant claims recite the same composition.
This is a provisional nonstatutory double patenting rejection.
Claims 28, 30-42 and 44 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of US11826349B2 in view of Gaetano (WO 2007/121913 A2; Nov. 1, 2007).
The ‘349 patent claims a pharmaceutical composition comprising a propellant component at least 90 weight % of which is 1,1-difluoroethane, a drug component comprising glycopyrrolate, budesonide and formoterol and the composition is free of acid stabilizers (claims 1-9, 11). ‘349 claims the composition comprising water and oxygen (claim 2) in the amount recited in instant claims. ‘349 claims the weight percent of the propellant component (claim 7-8) in the amount that reads on instant claims. ‘349 recites propellant contains 0.5 to 10 ppm of unsaturated impurities (claim 8). ‘349 recites the composition is free of perforated microstructures and other components (claim 11). ‘349 also teaches the composition in a metered dose inhaler and in the form of suspension (claim 1-2, 16).
While ‘349 teaches the composition comprises formoterol fumarate dihydrate, budesonide and glycopyrrolate, ‘349 does not teach wherein the composition comprising beclomethasone and tiotropium. However, this deficiency is cured by Gaetano.
As discussed supra, Gaetano teaches the composition can comprise anticholinergic atropine-like derivatives which include ipratropium bromide, oxitropium bromide, tiotropium bromide and glycopyrronium bromide (i.e. salt of glycopyrrolate) (see Page 7, line 11-25). Further, the reference teaches that long acting beta agonist such as formoterol and antimuscarinic agents in combination with inhaled corticosteroids (e.g., beclomethasone) have been proposed for the prevention and/or treatment of diseases (see Page 2, line 4-7). Therefore, it would have been obvious to one of ordinary skill in the art to comprise beclomethasone and/or tiotropium in the formulation because the combination of the different drugs was known to be beneficial in preventing or treating disease. Further, it would have been obvious to one of ordinary skill in the art to try and substitute one antimuscarinic agent/inhaled corticosteroid for another as a person with ordinary skill has good reason to pursue known options within his or her technical grasp. see MPEP 2141 KSR International CO. v. Teleflex Inc. 82 USPQ 2d 1385 (Supreme Court 2007).
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.
Even though the claims in the instant invention are directed towards a method and ‘349 application is directed towards a composition, the instant claims still read on ‘349 application claims because the instant claims recite the same composition.
Claims 28, 30-42 and 44 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of US11826348B2 in view of Gaetano (WO 2007/121913 A2; Nov. 1, 2007) and Noakes (WO 2012/156711 A1; Nov. 22, 2012).
The ‘348 claims a pharmaceutical composition comprising a propellant component at least 90 weight % of which is 1,1-difluoroethane, a drug component comprising glycopyrrolate, beclomethasone and formoterol and the composition is free of acid stabilizers (claim 1, 2, 8). ‘348 claims the composition comprising water and oxygen in the amount (claim 2) recited in instant claims. ‘348 claims the weight percent of the propellant component in the amount (claim 6, 7) that reads on instant claims. ‘348 recites propellant contains 0.5 to 10 ppm of unsaturated impurities (claim 8). ‘348 recites the composition is free of perforated microstructures and other components (claim 11). ‘348 also teach the composition in the form of solution and a metered dose inhaler (claim 1, 2, 8, 16).
The ‘348 does not claim the composition is in the form of suspension as recited in instant claims. However, Noakes cures this deficiency.
As discussed supra, Noakes teaches that incorporation of 1,1-difluoroethane as the propellant allows for a metered dose inhaler with low GWP in comparison with HFA-134a, reduced irritancy and forms stable suspensions or solutions.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified ‘348 to incorporate the teachings of Noakes and make the composition in the form of a suspension. One would have been motivated to do so because Noakes discusses problems related to HFA-134a propellant in solutions and suspensions and as discussed above, Noakes teaches that incorporation of 1,1-difluoroethane as the propellant allows for a metered dose inhaler with low GWP in comparison with HFA-134a, reduced irritancy and forms stable suspensions or solutions. Noakes teachings suggest that it was well known in the art that metered dosed inhalers can be made in the form of solution and suspension and it further provides motivation of achieving stable solution and suspension with the use of 1,1-difluoroethane as the propellant and therefore it would have been obvious to one of ordinary skill in the art to make the formulation in the form of a suspension.
‘348 does not teach wherein the composition comprises tiotropium. However, this deficiency is cured by Gaetano.
As discussed supra, Gaetano teaches the composition can comprise anticholinergic atropine-like derivatives which include ipratropium bromide, oxitropium bromide, tiotropium bromide and glycopyrronium bromide (i.e. salt of glycopyrrolate) (see Page 7, line 11-25). Further, the reference teaches that long acting beta agonist such as formoterol and antimuscarinic agents in combination with inhaled corticosteroids (e.g., beclomethasone) have been proposed for the prevention and/or treatment of diseases (see Page 2, line 4-7). Therefore, it would have been obvious to one of ordinary skill in the art to comprise tiotropium in the formulation because the combination of the different drugs was known to be beneficial in preventing or treating disease. Further, it would have been obvious to one of ordinary skill in the art to try and substitute one antimuscarinic agent for another as a person with ordinary skill has good reason to pursue known options within his or her technical grasp. see MPEP 2141 KSR International CO. v. Teleflex Inc. 82 USPQ 2d 1385 (Supreme Court 2007).
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.
Even though the claims in the instant invention are directed towards a method and ‘348 application is directed towards a composition, the instant claims still read on ‘348 application claims because the instant claims recite the same composition.
Claims 28, 30-42 and 44 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-21 of US11642330B2 in view of Gaetano (WO 2007/121913 A2; Nov. 1, 2007), Keller et al. (US 6,585,958 B1; Jul. 1, 2003) and Jager et al. (US 5,676,930; Oct. 14, 1997) as evidenced by Watson et al. (US 2010/0008997 A1; Jan. 14, 2010).
The ‘330 patent claims a pharmaceutical composition comprising a propellant component at least 90 weight % of which is 1,1-difluoroethane, a drug component comprising glycopyrrolate and formoterol (claim 1-7). ‘330 claims the weight percent of the propellant component in the amount that reads on instant claims (claim 4-7). ‘330 also teach the composition in the form of suspension, solution and a metered dose inhaler (claim 17, 19, 20). The drug component comprises from 0.01 to 2.5 weight % of the total weight of the pharmaceutical composition (claim 4). The claims of ‘330 do not require acid stabilizers in the formulation.
The ‘330 does not claim the composition comprises beclomethasone. However, this deficiency is cured by Gaetano.
Gaetano teaches the formulation can comprise two or more active drug substances which include corticosteroid such as beclomethasone, long acting beta agonist such as formoterol and long acting muscarinic antagonist. (see Page 7, line 11-22). Gaetano teaches that long acting beta agonist such as formoterol and antimuscarinic agents in combination with inhaled corticosteroids have been proposed for the prevention and/or treatment of diseases (see Page 2, line 4-7).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified ‘330 to incorporate the teachings of Gaetano and include beclomethasone because Gaetano teaches that long acting beta agonist such as formoterol and antimuscarinic agents in combination with inhaled corticosteroids have been proposed for the prevention and/or treatment of diseases (see Page 2, line 4-7). Therefore, it would have been obvious to one of ordinary skill in the art to include long acting muscarinic antagonist or formoterol with the beclomethasone agent in the formulation of ‘330 since these combinations were known in the art for treating respiratory diseases.
Regarding the amounts of water and oxygen, it would have been prima facie obvious to one of ordinary skill in the art to incorporate the teachings of Jagger and Keller and include water in small amount because Jagger teaches that though water present in the system interacts with medicament to produce decomposition or degradation products, a small amount of water can be added to aid in manufacturing. Further, as discussed supra and as evidenced by Watson, Naturally occurring levels of oxygen in water are typically no more than 10 ppm, which is considered to be a level of 100% dissolved oxygen. Thus, the presence of water would include dissolved oxygen in water of no more than 10 ppm. In addition, as discussed above, Keller teaches that displacing oxygen from the hydrofluoroalkanes results in improved storage stability of oxidation-sensitive active compounds but is silent on how much oxygen can be left since it would be difficult to keep the composition completely oxygen-free, which is also acknowledged in the instant specification (see Page 5, line 18-25). It would have been obvious to one skilled in the art to manipulate the amount of oxygen and determine an amount which would be optimal for the storage stability of oxidation-sensitive active compounds such formoterol taught by the combination of the prior art references above. Further, as discussed supra, Gaetano teaches metering valves fitted with gaskets made of chloroprene-based rubbers can be used to reduce the ingress of moisture which can adversely affect the stability of the drug (page 11, line 2-7). Therefore, one skilled in the art would have been strongly motivated to formulate the composition having very little amount of water content (such as the amount recited in instant claims) because Gaetano teaches that presence of moisture can adversely affect the stability of the drug.
With respect to the impurities recited in the instant claims, as discussed supra, the prior art teaches the same propellant and thus, it would necessarily be comprised of the similar amounts of impurities recited in the instant claims.
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.
Even though the claims in the instant invention are directed towards a method and ‘330 application is directed towards a composition, the instant claims still read on ‘330 application claims because the instant claims recite the same composition.
Claims 28, 30-42 and 44 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; 11,077,076; 11,311,502; 11,103,480; 11,260,052; 11,559,507; 11,559,505; 10,792,256; 10,888,546 in view of Gaetano (WO 2007/121913 A2; Nov. 1, 2007), Keller et al. (US 6,585,958 B1; Jul. 1, 2003) and Jager et al. (US 5,676,930; Oct. 14, 1997) as evidenced by Watson et al. (US 2010/0008997 A1; Jan. 14, 2010).
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 in view of Gaetano as evidenced by Watson et al.
Examined claims are drawn to a method of improving chemical stability of composition, composition comprising beclomethasone and formoterol compound and adding a propellant comprising 1,1-difluoroethane (R-152a) to the composition in the form of suspension.
Reference claims are drawn to a composition comprising at least one active agent, adding to the composition a propellant R-152a in the form of suspension wherein ethanol is optional and composition is free of polar excipient.
Specifically, the difference is that the examined claims require beclomethasone and formoterol, while reference claims require other active agents. The examined claims recite an amount of water and oxygen which isn’t recited in reference claims. This however is obvious in view of Gaetano and Keller and Jagger as evidenced by Watson et al.
As discussed supra, Gaetano teaches that long-acting beta agonist such as formoterol and antimuscarinic agents in combination with inhaled corticosteroids such as beclomethasone have been proposed for the prevention and/or treatment of diseases (see: Page 2, line 4-7; Claim 7). As taught by Gaetano 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.
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. 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 amounts of water and oxygen, it would have been prima facie obvious to one of ordinary skill in the art to incorporate the teachings of Jagger and Keller and include water in small amount because Jagger teaches that though water present in the system interacts with medicament to produce decomposition or degradation products, a small amount of water can be added to aid in manufacturing. Further, as discussed supra and as evidenced by Watson, Naturally occurring levels of oxygen in water are typically no more than 10 ppm, which is considered to be a level of 100% dissolved oxygen. Thus, the presence of water would include dissolved oxygen in water of no more than 10 ppm. In addition, as discussed above, Keller teaches that displacing oxygen from the hydrofluoroalkanes results in improved storage stability of oxidation-sensitive active compounds but is silent on how much oxygen can be left since it would be difficult to keep the composition completely oxygen-free, which is also acknowledged in the instant specification (see Page 5, line 18-25). It would have been obvious to one skilled in the art to manipulate the amount of oxygen and determine an amount which would be optimal for the storage stability of oxidation-sensitive active compounds such formoterol taught by the combination of the prior art references above. Further, as discussed supra, Gaetano teaches metering valves fitted with gaskets made of chloroprene-based rubbers can be used to reduce the ingress of moisture which can adversely affect the stability of the drug (page 11, line 2-7). Therefore, one skilled in the art would have been strongly motivated to formulate the composition having very little amount of water content (such as the amount recited in instant claims) because Gaetano teaches that presence of moisture can adversely affect the stability of the drug.
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 28, 30-42 and 44 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims of U.S. Patent No. 10,258,568; 10,258,569; 10,668,018 in view of Gaetano (WO 2007/121913 A2; Nov. 1, 2007) and Keller et al. (US 6,585,958 B1; Jul. 1, 2003) and Jager et al. (US 5,676,930; Oct. 14, 1997) as evidenced by Watson et al. (US 2010/0008997 A1; Jan. 14, 2010).
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 in view of Gaetano and Keller et al. as evidenced by Watson et al.
Examined claims are drawn to a method of improving chemical stability of composition, composition comprising beclomethasone and formoterol compound and adding a propellant comprising 1,1-difluoroethane (R-152a) to the composition in the form of suspension.
Reference claims are drawn to a composition comprising at least one active agent, adding to the composition a propellant R-152a and ethanol.
Specifically, the difference is that the examined claims require beclomethasone and formoterol, while reference claims require other active agents and ethanol. The examined claims recite an amount of water and oxygen which isn’t recited in reference claims. This however is obvious in view of Gaetano and Keller and Jagger as evidenced by Watson et al.
As discussed supra, Gaetano teaches that long-acting beta agonist such as formoterol and antimuscarinic agents in combination with inhaled corticosteroids such as beclomethasone have been proposed for the prevention and/or treatment of diseases (see: Page 2, line 4-7; Claim 7). As taught by Gaetano 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.
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. 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 discussed supra, Keller teaches that glycerol can also be added in place of ethanol in metered dose aerosols . Keller also provides a motivation that by addition of glycerol, suspension or solution aerosols having improved properties can often be obtained. Therefore, it would have been obvious to one of ordinary skill in the art to try and substitute the different cosolvents as a person with ordinary skill has good reason to pursue known options within his or her technical grasp. see MPEP 2141 KSR International CO. v. Teleflex Inc. 82 USPQ 2d 1385 (Supreme Court 2007).
The other difference is that the reference claims do not teach that the formulation is a suspension. However, as discussed supra, Keller provides a motivation that by addition of glycerol, suspension or solution aerosols having improved properties can often be obtained. Thus, it would have been obvious to formulate the composition in the form of a suspension or solution as both types of forms are taught to be used in metered dose inhalers.
Regarding the amounts of water and oxygen, it would have been prima facie obvious to one of ordinary skill in the art to incorporate the teachings of Jagger and Keller and include water in small amount because Jagger teaches that though water present in the system interacts with medicament to produce decomposition or degradation products, a small amount of water can be added to aid in manufacturing. Further, as discussed supra and as evidenced by Watson, Naturally occurring levels of oxygen in water are typically no more than 10 ppm, which is considered to be a level of 100% dissolved oxygen. Thus, the presence of water would include dissolved oxygen in water of no more than 10 ppm. In addition, as discussed above, Keller teaches that displacing oxygen from the hydrofluoroalkanes results in improved storage stability of oxidation-sensitive active compounds but is silent on how much oxygen can be left since it would be difficult to keep the composition completely oxygen-free, which is also acknowledged in the instant specification (see Page 5, line 18-25). It would have been obvious to one skilled in the art to manipulate the amount of oxygen and determine an amount which would be optimal for the storage stability of oxidation-sensitive active compounds such formoterol taught by the combination of the prior art references above. Further, as discussed supra, Gaetano teaches metering valves fitted with gaskets made of chloroprene-based rubbers can be used to reduce the ingress of moisture which can adversely affect the stability of the drug (page 11, line 2-7). Therefore, one skilled in the art would have been strongly motivated to formulate the composition having very little amount of water content (such as the amount recited in instant claims) because Gaetano teaches that presence of moisture can adversely affect the stability of the drug.
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 28, 30-42 and 44 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims of copending Application No. 17/944,637; 17/944,666; 17/969,250 in view of Gaetano (WO 2007/121913 A2; Nov. 1, 2007) and Keller et al. (US 6,585,958 B1; Jul. 1, 2003) as evidenced by Watson et al. (US 2010/0008997 A1; Jan. 14, 2010).
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 in view of Gaetano and Keller et al. as evidenced by Watson et al.
Examined claims are drawn to a method of improving chemical stability of composition, composition comprising beclomethasone and formoterol compound and adding a propellant comprising 1,1-difluoroethane (R-152a) to the composition in the form of suspension.
Reference claims are drawn to a composition comprising at least one active agent, adding to the composition a propellant R-152a and ethanol.
Specifically, the difference is that the examined claims require beclomethasone and formoterol, while reference claims require other active agents and ethanol. This however is obvious in view of Gaetano and Keller et al. as evidenced by Watson et al.
As discussed supra, Gaetano teaches that long-acting beta agonist such as formoterol and antimuscarinic agents in combination with inhaled corticosteroids such as beclomethasone have been proposed for the prevention and/or treatment of diseases (see: Page 2, line 4-7; Claim 7). As taught by Gaetano 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.
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. 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).
Also, reference claims recite less than 500 ppm water in the composition and, as discussed supra and as evidenced by Watson, Naturally occurring levels of oxygen in water are typically no more than 10 ppm, which is considered to be a level of 100% dissolved oxygen. Thus, the presence of water would include dissolved oxygen in water of no more than 10 ppm.
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.
Claims 28, 30-42 and 44 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims of copending Application No. 18/489,133 in view of Gaetano (WO 2007/121913 A2; Nov. 1, 2007) and Keller et al. (US 6,585,958 B1; Jul. 1, 2003) as evidenced by Watson et al. (US 2010/0008997 A1; Jan. 14, 2010).
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 in view of Gaetano and Keller et al. as evidenced by Watson et al.
Examined claims are drawn to a method of improving chemical stability of composition, composition comprising beclomethasone and formoterol compound and adding a propellant comprising 1,1-difluoroethane (R-152a) to the composition in the form of suspension.
Reference claims are drawn to a composition comprising at least one active agent, adding to the composition a propellant R-152a and optionally ethanol.
Specifically, the difference is that the examined claims require beclomethasone and formoterol, while reference claims require other active agents. This however is obvious in view of Gaetano and Keller et al. as evidenced by Watson et al.
As discussed supra, Keller teaches that glycerol can also be added in place of ethanol in metered dose aerosols . Keller also provides a motivation that by addition of glycerol, suspension or solution aerosols having improved properties can often be obtained. Therefore, it would have been obvious to one of ordinary skill in the art to try and substitute the different cosolvents as a person with ordinary skill has good reason to pursue known options within his or her technical grasp. see MPEP 2141 KSR International CO. v. Teleflex Inc. 82 USPQ 2d 1385 (Supreme Court 2007).
As discussed supra, Gaetano teaches that long-acting beta agonist such as formoterol and antimuscarinic agents in combination with inhaled corticosteroids such as beclomethasone have been proposed for the prevention and/or treatment of diseases (see: Page 2, line 4-7; Claim 7). As taught by Gaetano 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.
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. 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 other difference is that the reference claims do not teach that the formulation is a suspension. However, as discussed supra, Keller provides a motivation that by addition of glycerol, suspension or solution aerosols having improved properties can often be obtained. Thus, it would have been obvious to formulate the composition in the form of a suspension or solution as both types of forms are taught to be used in metered dose inhalers.
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.
Claims 28, 30-42 and 44 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims of copending Application No. 18/489,150 in view of Gaetano (WO 2007/121913 A2; Nov. 1, 2007).
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 in view of Gaetano and Keller et al. as evidenced by Watson et al.
Examined claims are drawn to a method of improving chemical stability of composition, composition comprising beclomethasone and formoterol compound and adding a propellant comprising 1,1-difluoroethane (R-152a) to the composition in the form of suspension.
Reference claims are drawn to a composition comprising at least one active agent, adding to the composition a propellant R-152a and optionally ethanol.
Specifically, the difference is that the examined claims require beclomethasone and formoterol, while reference claims require other active agents. This however is obvious in view of Gaetano.
As discussed supra, Gaetano teaches that long-acting beta agonist such as formoterol and antimuscarinic agents in combination with inhaled corticosteroids such as beclomethasone have been proposed for the prevention and/or treatment of diseases (see: Page 2, line 4-7; Claim 7). As taught by Gaetano 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.
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. 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).
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.
Response to Arguments
Applicant requested the rejections be reconsidered in view of the amended claims. Also argued that the rejections be held in abeyance until there is indication of allowably subject matter.
In response, the amended claims do not overcome the double patenting rejections discussed above. Since applicant’s arguments regarding the double patenting rejections are not found persuasive, the rejections are maintained at this time.
Regarding US11,642,330, Applicant argued that ‘330 teaches glycopyrrolate and formoterol is the sole drug component and teach away from including beclomethasone.
In response, the examiner argues that use of long acting beta agonists such as formoterol, antimuscarinic agents such as glycopyrrolate and inhaled corticosteroids such as beclomethasone, alone or in combination in inhaled metered dose inhalers for pulmonary disorders was known in the art as suggested by Gaetano. Gaetano teaches that long-acting beta agonist such as formoterol and antimuscarinic agents in combination with inhaled corticosteroids such as beclomethasone have been proposed for the prevention and/or treatment of diseases (see: Page 2, line 4-7; Claim 7). Thus, one skilled in the art would have found it obvious to change the combination of the active drug ingredients and utilize a combination that would be optimal in treating the pulmonary disorders. Specifically, because these drug classes and the different combinations of these drug classes were known in the art for treating pulmonary disorders.
Regarding the collective double patenting rejections because the number of patents applied under obviousness type double patenting being very large and based on similar analysis, Applicant argued that examiner’s collective rejection of all examination claims over the unspecified reference claims constitutes legal error. Applicant pointed to MPEP 804 II.B.2. (see: page 15-16 of Remarks filed on 12/15/2025).
In response, as disclosed in the remarks by applicants, the MPEP states: Any nonstatutory double patenting rejection made under the obviousness analysis should make clear:
(A) The differences between the inventions defined by the conflicting claims — a claim in the patent compared to a claim in the application; and
(B) The reasons why a person of ordinary skill in the art would conclude that the invention defined in the claim at issue would have been an obvious variation of the invention defined in a claim in the patent.
In the collective rejections made above (for example over claims of U.S. Patent No. 11,690,823; 11,179,366; 11,077,076; 11,311,502; 11,103,480; 11,260,052; 11,559,507; 10,792,256; 10,888,546), the examiner states that the examined claims are drawn to a composition comprising beclomethasone and formoterol compound, glycerol and a propellant comprising 1,1-difluoroethane (R-152a).
Then the examiner states that the reference claims are drawn to a composition comprising at least one active agent, propellant R-152a and ethanol.
Then the examiner states the differences between the inventions defined by the conflicting claims, specifically, the difference is that the examined claims require beclomethasone and formoterol, while reference claims require other active agents. Also, the examined claims require glycerol, while reference claims do not teach this.
The reasons why a person of ordinary skill in the art would conclude that the invention defined in the claim at issue would have been an obvious variation of the invention defined in a claim in the patent is also discussed in the rejection. Specifically, the examiner discusses how the difference is obvious in view of Gaetano and Keller et al. as evidenced by Watson et al.
Further, the rejections state “over the claims of” which include all the claims of the patents/copending applications. Applicant also argued that the examiner does not specify the active ingredients in the reference claims. In response, it is argued that the examiner points out the reference claims are drawn to a composition comprising at least one active ingredient and the difference between the actives of the examined claims verses the reference claims. The applicant have not pointed out what exactly is unclear regarding the rejection or how the rejection is nonobvious. Therefore, applicant’s arguments regarding the grouping together of reference claims are not found persuasive at this time.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALI SAEED whose telephone number is (571)272-2371. The examiner can normally be reached M-F 8-5 EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, SUE X LIU can be reached at 5712725539. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/A.S/Examiner, Art Unit 1616
/SUE X LIU/Supervisory Patent Examiner, Art Unit 1616