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 12/3/2025 is acknowledged. Claims 25-41 and 43-56 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Rejection(s) not reiterated from the previous Office Action are hereby withdrawn.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Withdrawn Rejections/Objections
The rejections of claim 42 and 57 under 112(b) has been withdrawn to cancellation of claims 42 and 57 in the presently amended claims.
Claim interpretation
Claims 40 and 55 recite the composition "consisting essentially of". The "consisting essentially of" language recited in the claims still allows for inclusion of other components not recited in the instant claims. The transitional phrase "consisting essentially of" limits the scope of a claim to the specified materials or steps "and those that do not materially affect the basic and novel characteristic(s)" of the claimed invention. In re Herz, 537 F.2d 549, 551-52, 190 USPQ 461, 463 (CCPA 1976). For the purposes of searching for and applying prior art under 35 U.S.C. 102 and 103, absent a clear indication in the specification or claims of what the basic and novel characteristics actually are, "consisting essentially of" will be construed as equivalent to "comprising." See, e.g., PPG, 156 F.3d at 1355, 48 USPQ2d at 1355. If an applicant contends that additional steps or materials in the prior art are excluded by the recitation of "consisting essentially of," applicant has the burden of showing that the introduction of additional steps or components would materially change the characteristics of applicant’s invention. In re De Lajarte, 337 F.2d 870, 143 USPQ 256 (CCPA 1964). See also Ex parte Hoffman, 12 USPQ2d 1061, 1063-64 (Bd. Pat. App. & Inter. 1989). See MPEP 2111. Thus, in the instant case, "consisting essentially of" is interpreted as "comprising of" which does not exclude ingredients not positively recited in the claims.
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 25, 26, 28-31 and 33-41, 43-44, 45, 47-50, 52-56 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 Lewis (EP1787639 B1; Mar. 23, 2011) and Watson et al. (US 2010/0008997 A1; Jan. 14, 2010).
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 (claims 2-4). 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 or acid stabilizers in the formulation and therefore reads on the claimed limitations wherein the formulation is free of surfactants, acid stabilizers or perforated microstructures. 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.
Regarding the claimed limitations wherein a metered dose inhaler is fitted with the sealed and pressurized container, as stated above, Gaetano teaches solution formulations for pressurized metered dose inhaler. 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.
The teachings of Gaetano have been set forth above.
Gaetano does not teach that the propellant component is 1,1-difluoroethane 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 and preferably consisting entirely of 1,1-difluoroethane, ethanol, and beclomethasone diproprionate 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-difluoroethan (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 also does not teach the total amount of the active drug components in the composition as required in the instant claims. 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 less than 1000 ppm but greater 0.5 ppm of dissolved oxygen as recited in instant claim 2. However, these deficiencies are cured by Keller et al. and Jager et al. as evidenced by Watson et al. and Lewis 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 1,1difluoroethane 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). As evidenced by Lewis, formoterol in HFA formulations suffer of chemical stability problems due to their susceptibility to oxidative conditions (see Para 0010). Formoterol is taught as the active substance by Gaetano and is recited in the instant claims. 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.
With regards to 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 (e.g., HFA 152a providing stable solution or suspension). The structure of the prior art compositions is the same as the instantly claimed composition. 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 2.5%. 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 16-17 and 38-39 because both of these examples read on the claimed percentage of total impurities. Therefore, even when the formulations of the prior art 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.
With respect to instant claim 36, the prior art (Noakes et al.) teaches the same propellant (i.e., HFA-152a) and thus this propellant would necessarily have the properties (i.e., similar amount of unsaturated impurities) recited in the instant claims.
With respect to claims 41 and 56 which recite the composition consisting of the drug component and the propellant component. Independent claims 25 and 43 recite a drug component “comprises” and the comprising language does not exclude additional components in the drug component. Gaetano and Noakes teach pharmaceutical active ingredients dissolved in ethanol and this combination of active ingredient and ethanol reads on the “drug component comprising” (which can comprise other components) and the composition consisting of the drug component and the propellant 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.
Claims 7, 32, 46, 51 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 Lewis (EP1787639 B1; Mar. 23, 2011) and Watson et al. (US 2010/0008997 A1; Jan. 14, 2010) as applied to claims 25, 26, 28-31 and 33-41, 43-44, 45, 47-50, 52-56 and further in view of Berry (Drug Development and Industrial Pharmacy, Vol. 30, No. 7, Pg. 705-714, Aug. 09, 2004).
The teachings of the above references have been set forth above.
The above references do not expressly teach that the drug components are in micronized form. However, this deficiency is cured by Berry.
Berry discloses a study that was designed to investigate the impact of micronized active pharmaceutical ingredient (API) particle size on the aerodynamic particle size distribution (PSD) profile and the particle size stability of metered dose inhaler containing propellant HFA-227 and corticosteroid. The study showed that samples containing larger size API particles were less stable with respect to their aerodynamic PSD than those with smaller size API particles (Abstract). The reference further discloses that a metered dose inhaler used in the treatment of pulmonary diseases is often comprised of micronized active pharmaceutical ingredient (Introduction).
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 Berry because Berry teaches metered dose inhalers used in the treatment of pulmonary diseases are often comprised of micronized active pharmaceutical ingredient wherein the smaller size API particles were more stable than larger size API particles. This suggests that it was well known in the art before the effective filing date of the instant invention that metered dose inhalers comprise micronized active drug ingredient and therefore it would have been obvious to comprise the claimed drug components in micronized form.
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 in Jager medicinal aerosol solution formulations are stabilized by including acids in its formulations and that acids provide stability against degradation or decomposition of the medicament resulting largely from interaction of the medicament with the cosolvent and/or water present in the solution formulation. Applicant stated Jager teaches that small amounts of water may be added to aid in manufacturing since its formulation includes acids and water-triggered degradation or decomposition of the medicament would be prevented by the acids in the formulation. It was argued that the instant claims require the composition is free of acid stabilizers and Jager does not teach a formulation without acid, thus water contents in the Jager formulation which contains acid would not provide any guidance as to how much water should be included in a composition which is free of acid stabilizers.
In response, firstly the examiner argues that none of the instant claims require the composition is free of acid stabilizer. Further, it is argued that Jager includes acids in the formulation to provide stability of the medicament, as acknowledged by the applicant. As discussed supra, Noakes teaches the use of HFA-152a which would provide reduced GWP and stable suspensions or solutions, and Noakes does not require acid stabilizer. Since Noakes already addresses the stability issues of the medicament, one skilled in the art would have had a reasonable expectation of success in including water to aid in manufacturing without adding acid stabilizers because Noakes already addresses the issues related to stability of the medicament and teaches that the propellants taught in Noakes exhibit improved stability. Thus, one skilled in the art would have been motivated to include the amount of water taught by Jager to aid in manufacturing without having to add acid stabilizers to stabilize the formulation.
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 further argued that instant claims recite the composition contains less than 1000 ppm but greater than 0.5 ppm of dissolved oxygen and that Watson teaches oxygen level in water. It was argued that Watson fails to teach any dissolved oxygen level in a propellant and Keller and Lewis do not teach or cure this deficiency.
In response, as discussed supra, Watson teaches 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. Watson clearly teaches dissolved oxygen and thus, applicant’s arguments regarding the cited art not teaching dissolved oxygen are not found persuasive.
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 25-41 and 43-56 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 Berry (Drug Development and Industrial Pharmacy, Vol. 30, No. 7, Pg. 705-714, Aug. 09, 2004) as evidenced by Watson et al. (US 2010/0008997 A1; Jan. 14, 2010).
The ‘156 application recites a pharmaceutical composition comprising 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 all read on instant claims. 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.). ‘156 recite the drug component additionally comprises long acting muscarinic antagonists. ‘156 recite weight % of the propellant component that reads on instant claims. ‘156 recites propellant component contains 0.5 to 10 ppm of unsaturated impurities. ‘156 recite the composition is free of polar excipient. ‘156 recite the composition is free of surfactants, perforated microstructures and acid stabilizers. ‘156 claims the weight of total impurities which read on instant claims 16 and 17. ‘156 recite the composition in the form of suspension. ‘156 recites a metered dose inhaler.
The ‘156 application does not expressly teach that the drug components are in micronized form as recited in instant claims 3 and 8. However, this deficiency is cured by Berry.
As discussed supra, Berry discloses a study that was designed to investigate the impact of micronized active pharmaceutical ingredient (API) particle size on the aerodynamic particle size distribution (PSD) profile and the particle size stability of a suspension metered dose inhaler containing propellant HFA-227 and corticosteroid. The study showed that samples containing larger size API particles were less stable with respect to their aerodynamic PSD than those with smaller size API particles (Abstract). The reference further discloses that a metered dose inhaler used in the treatment of pulmonary diseases is often comprised of micronized active pharmaceutical ingredient suspended in a propellant (Introduction).
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 ‘156 to incorporate the teachings of Berry because Berry teaches metered dose inhalers used in the treatment of pulmonary diseases are often comprised of micronized active pharmaceutical ingredient suspended in a propellant. This suggests that it was well known in the art before the effective filing date of the instant invention that metered dose inhalers in suspension form comprise micronized active drug ingredient and therefore it would have been obvious to comprise the claimed drug components in micronized form.
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.
This is a provisional nonstatutory double patenting rejection.
Claims 25-41 and 43-56 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) and Berry (Drug Development and Industrial Pharmacy, Vol. 30, No. 7, Pg. 705-714, Aug. 09, 2004) as evidenced by Watson et al. (US 2010/0008997 A1; Jan. 14, 2010).
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 and beclomethasone dipropionate (claims 6-9). ‘585 claims the composition comprising water and oxygen (claims 4-5) in the amount recited in instant claims. 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.). ‘585 claims the weight percent of the propellant component in the amount (claim 10, 11, 24) that reads on instant claims. ‘585 recites propellant contains 0.5 to 10 ppm of unsaturated impurities. ‘585 recites the composition is free of perforated microstructures and other components (claim 15). ‘585 also teach the composition in a metered dose inhaler (claim 1, 13, 22, 24, 25, 26). ‘585 teaches the composition delivers the drug component in the same proportion as they occur in the composition. ‘585 recites the composition is free of polar excipient.
The ‘585 application does not expressly teach that the drug components are in micronized form as recited in instant claims. However, this deficiency is cured by Berry.
As discussed supra, Berry discloses a study that was designed to investigate the impact of micronized active pharmaceutical ingredient (API) particle size on the aerodynamic particle size distribution (PSD) profile and the particle size stability of a suspension metered dose inhaler containing propellant HFA-227 and corticosteroid. The study showed that samples containing larger size API particles were less stable with respect to their aerodynamic PSD than those with smaller size API particles (Abstract). The reference further discloses that a metered dose inhaler used in the treatment of pulmonary diseases is often comprised of micronized active pharmaceutical ingredient suspended in a propellant (Introduction).
The ‘585 application does not claim the composition comprises a salt of glycopyrrolate as the long acting muscarinic antagonist recited in instant claims. 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).
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 ‘585 to incorporate the teachings of Berry because Berry teaches metered dose inhalers used in the treatment of pulmonary diseases are often comprised of micronized active pharmaceutical ingredient suspended in a propellant. This suggests that it was well known in the art before the effective filing date of the instant invention that metered dose inhalers in suspension form comprise micronized active drug ingredient and therefore it would have been obvious to comprise the claimed drug components in micronized form.
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.
This is a provisional nonstatutory double patenting rejection.
Claims 25-41 and 43-56 are provisionally 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) as evidenced by Watson et al. (US 2010/0008997 A1; Jan. 14, 2010).
The ‘349 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 and polar excipients (claims 1-9, 11). ‘349 claims the composition comprising water and oxygen in the amount (claim 2) recited in instant claims. 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.). ‘349 claims the weight percent of the propellant component in the amount (claim 7-8) 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 teach the composition in the form of suspension and a metered dose inhaler (claim 1-2, 16). ‘349 also teaches the drug components in a micronized form (claim 5).
The ‘349 does not claim the composition comprises beclomethasone. However, this deficiency is cured by Gaetano.
Gaetano teaches corticosteroid selected for the formulation include beclomethasone dipropionate and budesonide (Claim 7). 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 beclomethasone in place of budesonide in the formulation because the combination of these 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 corticosteroid agent already taught by ‘349 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.
Claims 25-41 and 43-56 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of US11826348B2 in view of Noakes (WO 2012/156711 A1; Nov. 22, 2012) as evidenced by Watson et al. (US 2010/0008997 A1; Jan. 14, 2010).
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 and polar excipients (claim 1, 2, 8). ‘348 claims the composition comprising water and oxygen in the amount (claim 2) recited in instant claims. 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.). ‘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). ‘348 also teaches the drug components in a micronized form (claim 5).
The ’348 is silent on the drug component concentration. However, Noakes cures this deficiency.
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 ‘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.
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 include the drug component in the amount taught by Noakes. It would have been obvious to one skilled in the art to look towards the teachings of Noakes for the total amount drug componentsl to add in the composition since such amounts were known in the art as shown in Noakes. Particularly, it would have been obvious to manipulate the amount of the active drug component based on parameters such as severity of disease or size/weight of subject. 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).
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 25-41 and 43-56 are provisionally 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) and Berry (Drug Development and Industrial Pharmacy, Vol. 30, No. 7, Pg. 705-714, Aug. 09, 2004).
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). Composition does not require a polar excipient. The claims of ‘330 also do not require acid stabilizers in the formulation.
The ‘330 does not expressly teach that the drug components are in micronized form as recited in instant claims 3 and 8. However, this deficiency is cured by Berry.
As discussed supra, Berry discloses a study that was designed to investigate the impact of micronized active pharmaceutical ingredient (API) particle size on the aerodynamic particle size distribution (PSD) profile and the particle size stability of a suspension metered dose inhaler containing propellant HFA-227 and corticosteroid. The study showed that samples containing larger size API particles were less stable with respect to their aerodynamic PSD than those with smaller size API particles (Abstract). The reference further discloses that a metered dose inhaler used in the treatment of pulmonary diseases is often comprised of micronized active pharmaceutical ingredient suspended in a propellant (Introduction).
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 Berry because Berry teaches metered dose inhalers used in the treatment of pulmonary diseases are often comprised of micronized active pharmaceutical ingredient suspended in a propellant. This suggests that it was well known in the art before the effective filing date of the instant invention that metered dose inhalers in suspension form comprise micronized active drug ingredient and therefore it would have been obvious to comprise the claimed drug components in micronized form.
The ‘330 does not claim the composition comprises beclomethasone. However, this deficiency is cured 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). Therefore, it would have been obvious to one of ordinary skill in the art to comprise beclomethasone in the formulation because the combination of these different drugs was known to be beneficial in preventing or treating disease.
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 amount 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.
Claims 25-41 and 43-56 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) 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 composition comprising beclomethasone and formoterol compound and a propellant comprising 1,1-difluoroethane (R-152a) in the form of suspension.
Reference claims are drawn to a composition comprising at least one active agent, 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. This however is obvious in view of Gaetano 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 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 25-41 and 43-56 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) 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 composition comprising beclomethasone and formoterol compound and a propellant comprising 1,1-difluoroethane (R-152a) in the form of suspension.
Reference claims are drawn to a composition comprising at least one active agent, 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, 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).
As discussed supra, the examiner interprets free of polar excipient to be free of ethanol and thus glycerol can be included in the composition. Thus, replacing ethanol with glycerol per the teachings of Keller reads on wherein the composition is free of polar excipients.
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.
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 25-41 and 43-56 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 composition comprising beclomethasone and formoterol compound, and a propellant comprising 1,1-difluoroethane (R-152a) in suspension form.
Reference claims are drawn to a composition comprising at least one active agent, 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, 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).
As discussed supra, the examiner interprets free of polar excipient to be free of ethanol and thus glycerol can be included in the composition. Thus, replacing ethanol with glycerol per the teachings of Keller reads on wherein the composition is free of polar excipients.
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 25-41 and 43-56 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 composition comprising beclomethasone and formoterol compound, and a propellant comprising 1,1-difluoroethane (R-152a) in suspension form.
Reference claims are drawn to a composition comprising at least one active agent, 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 25-41 and 43-56 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) 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 composition comprising beclomethasone and formoterol compound, and a propellant comprising 1,1-difluoroethane (R-152a) in suspension form.
Reference claims are drawn to a composition comprising at least one active agent, 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. Also, the examined claims require glycerol, while reference claims do not teach this. 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).
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.
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/A.S/Examiner, Art Unit 1616
/SUE X LIU/Supervisory Patent Examiner, Art Unit 1616