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 .
Status of Action/Claims
Receipt of Remarks/Amendments filed on 12/15/2025 is acknowledged. Claims 1, 6-18, 20 and 22-26 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Rejection(s) not reiterated from the previous Office Action are hereby withdrawn.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Withdrawn Rejections/Objections
The rejections of claims 22-24 and 27-30 under 112(b) has been withdrawn due to appropriate claim amendments.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 1, 6-13, 15-18, 20 and 22-26 are rejected under 35 U.S.C. 103 as being unpatentable over Malhotra et al. (US 2015/0250713 A1; Sep. 10, 2015) in view of Noakes (WO 2012/156711 A1; Nov. 22, 2012), DuPont (“1,1-Difluoroethane (HFC-152a)”, SIDS Initial Assessment Report For SIAM 22, UNEP Publications, Jun. 29, 2006) (previously cited) and Amighi et al. (US2011/0311618A1; Dec. 22, 2011) as evidenced by Watson et al. (US 2010/0008997 A1; Jan. 14, 2010).
Malhotra throughout the reference teaches pharmaceutical composition comprising tiotropium, a hydrofluoroalkane (HFA) propellant, and optionally one or more pharmaceutically acceptable excipient. It also teaches a process for preparing such a composition, and the use thereof in medicine, in particular for prophylaxis and treatment of respiratory disorder. (see: Abstract).
Malhotra in example 3 discloses a composition comprising tiotropium bromide and the adding HFA-227 propellant in the composition. Example 3 also discloses the composition comprising Polyvinylpyrrolidone (PVP) and polyethylene glycol (PEG). Example 3 also teaches the composition in the form of a suspension. While example 3 discloses the composition comprising HFA-227 propellant, Malhotra teaches other examples of suitable HFA propellants are HFA-32, HFA-143(a) and HFA-152a (Para 0051). Malhotra also teaches the composition preferably comprises tiotropium bromide monohydrate or tiotropium bromide anhydrate (Para 0065). The reference also teaches the composition comprising tiotropium bromide is an aerosol composition formulated for delivery using a pressurized metered dose inhaler (Para 0065 and 0041). A 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 and this reads on the claimed limitation wherein the sealed and pressurized container is operatively coupled with a metered dose inhaler. Example 3 of Malhotra does not include any acid stabilizers and thus reads on the claimed recitation wherein the composition is free of acid stabilizers. Further, example 3 of the reference does not disclose any perforated microstructures or salts of cromoglycic acid and nedocromil in the composition and thus reads on instant claim 15. Example 3 of the reference also does not teach adding ethanol in the composition and thus reads on wherein the composition is free of polar excipient.
The teachings of Malhotra have been set forth above.
Malhotra does not expressly teach including further active ingredients in example 3. However, Malhotra does teach the composition can comprise further one or more active agents which include formoterol, salmeterol, olodaterol and beclomethasone (see: claim 7).
As discussed supra, Malhotra in example 3 discloses the composition comprising HFA-227 propellant. Malhotra teaches other examples of suitable HFA propellants are HFA-32, HFA-143(a) and HFA-152a (Para 0051). While Malhotra teaches HFA-152a propellant as a suitable propellant in the composition, it does not explicitly exemplify using the HFA-152a propellant. However, this deficiency is 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 (HFA-152a) (Abstract; Claims; Page 3, lines 21-31). 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) and 1,1,1,2,3,3,3-heptafluoropropane (i.e., HFA-227) have high global warming potentials (GWP), 1430 and 3220 respectively, 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 and HFA 227, 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). Noakes discloses the HFA-152a propellant which fulfills these needs and 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).
Malhotra does not teach the amount of water and oxygen content in the metered dose inhalers. However, this deficiency is cured by DuPont, Watson et al. and Amighi et al.
The DuPont reference teaches that the HFA-152a propellant include low level (ppm) of water. (pg. 5 and pg. 24). As evidenced by Watson, naturally occurring levels of oxygen in water are typically no more than 10 ppm (see: Para 0200 of Watson et al.). Thus, the presence of water would include oxygen in water of no more than 10 ppm.
Amighi throughout the reference teaches inhalable compositions comprising tiotropium. Amighi discloses that tiotropium is oxidation sensitive wherein tiotropium undergoes chemical degradation due oxidation. (see: Abstract; Para 0031).
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 comprise further one or more active agents which include formoterol, salmeterol, olodaterol and beclomethasone as taught by Malhotra. One would have been motivated to do so because Malhotra clearly teaches further active agents such as formoterol, salmeterol, olodaterol and beclomethasone can be included. 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).
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 Malhotra to incorporate the teachings of Noakes and substitute HFA-227 propellant exemplified by Malhotra with HFA-152a propellant taught by Noakes. One would have been motivated to do so because, as discussed supra, Noakes states that there is a need for a metered dose inhaler formulation that has a reduced GWP in comparison with HFA-134 and HFA 227, has acceptable flammability and toxicity performance and which forms stable suspensions or solutions with a range of pharmaceutical actives and discloses the HFA-152a propellant which fulfills these needs. Further, one would have had a reasonable expectation of success because Malhotra already discloses HFA-152a as an example of a suitable propellant to be included in the composition and Noakes provides further motivation to replace HFA-227 with HFA-152a.
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 DuPont and Watson regarding water and oxygen content. Malhotra teaches that tiotropium is an extremely moisture sensitive drug and formulations containing tiotropium undergo hydrolytic degradation which results in an unstable formulation (para 0010). Malhotra and Noakes references already teach the 1,1-difluoroethane propellant and the DuPont reference teaches that the HFA-152a (1,1-difluoroethane) propellant include low level (ppm) of water (pg. 5 and pg. 24). It would have been obvious to one skilled in the art ensure that low level of water content is contained in the formulation because tiotropium is a moisture sensitive drug and since DuPont already teaches the water content in HFA-152a propellant is low level (ppm) of water, one skilled in the art would have been motivated to ensure that the water content is kept low, such as in the amount recited in the instant claims. Further, as evidenced by Watson, naturally occurring levels of oxygen in water are typically no more than 10 ppm (see: Para 0200 of Watson et al.). Further, as discussed supra, Amighi discloses that tiotropium is oxidation sensitive wherein tiotropium undergoes chemical degradation due oxidation. Thus, it would have been obvious to one skilled in the art to ensure that the oxygen content in the composition is kept low (such as less than 1000 ppm as recited in instant claims) to avoid chemical degradation of tiotropium due to oxidation.
With respect to the claimed drug component which comprises tiotropium bromide monohydrate, as discussed supra, Malhotra teaches the composition preferably comprises tiotropium bromide monohydrate or tiotropium bromide anhydrate. 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).
With respect to claims 16-18 and 20, the structure of the prior art composition is the same as 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 recited in claims 16 and 17. Further, the same amount of tiotropium bromide monohydrate would necessarily be present in the composition after storage under the conditions recited in claim 18. Also, the composition when delivered would necessarily yield the same amount of fine particle fraction of the tiotropium bromide monohydrate after storage under the conditions recited in claim 20.
With respect to claim 23, the structure of the prior art composition and method is the same as the composition and method recited in the instant claims. Therefore, the formulations comprising HFA-152a propellant along with other instantly claimed components would necessarily yield the same amount of fine particle fraction of the tiotropium bromide monohydrate after storage under the conditions recited in claim 23.
With respect to instant claim 12, the prior art (Malhotra et al. and Noakes et al.) teach 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.
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 14 is rejected under 35 U.S.C. 103 as being unpatentable over Malhotra et al. (US 2015/0250713 A1; Sep. 10, 2015) in view of Noakes (WO 2012/156711 A1; Nov. 22, 2012), DuPont (“1,1-Difluoroethane (HFC-152a)”, SIDS Initial Assessment Report For SIAM 22, UNEP Publications, Jun. 29, 2006) (previously cited) and Amighi et al. (US2011/0311618A1; Dec. 22, 2011) as evidenced by Watson et al. (US 2010/0008997 A1; Jan. 14, 2010) as applied to claims 1, 6-13, 15-18, 20 and 22-26 above.
The teachings of the above cited references have been set forth above.
Malhotra does not explicitly disclose the composition comprising a polar excipient which is ethanol as instantly claimed in claim 14. However, this deficiency is cured by Noakes.
As discussed supra, 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 (HFA-152a). Noakes further teaches wherein ethanol can be used as a solvent (Abstract; Claims; Page 3, lines 21-31). Noakes discloses the HFA-152a propellant and that the composition consisting entirely of 1,1-difluoroethane (HFA-152a) as the propellant reduces the amount of ethanol required to dissolve the drug in the composition (see Page 4, line 12-19).
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 Malhotra to incorporate the teachings of Noakes and include ethanol as taught by Noakes into the composition of Malhotra. One would have been motivated to do so because Malhotra teaches that its composition can optionally comprise one or more pharmaceutically acceptable excipient such as co-solvents and Noakes discloses ethanol as solvent to dissolve the drug in the composition (see: Page 4, line 12-19 of Noakes). Thus, it would have been obvious to one skilled in the art to include ethanol in the composition with a reasonable expectation of success because Malhotra allows the inclusion of further excipients such as co-solvents and Noakes discloses ethanol as a solvent used to dissolve the drug in metered dose inhaler formulations.
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 that the cited references do not teach the water and oxygen amount recited in the amended independent claims. Specifically, it is argued that HFA-152a may be manufactured by entities other than DuPont and whether the DuPont HFA-152a includes water or not is irrelevant unless the Examiner shows HFA-152a, regardless of manufacturers, inherently includes the claimed amount of water. The art of record does not show that all other HFA-152a contains the same water amount as DuPont HFA-152a. Applicant also argued that low level water is an impurity in the DuPont HFA-152a and an impurity would not have motivated one skilled in the art to keep the water amount in the composition low. Applicant argued the cited references do not teach the specific amount of water and oxygen as claimed.
In response, DuPont discloses the chemical/physical properties of the HFA-152a propellant and DuPont discloses that typical impurities in HFA-152a include low level (ppm) water (see e.g., page 5). Applicant have not provided any evidence that teaches or suggests that HFA-152a propellant have properties (e.g., water as an impurity in low level (ppm)) which are different than what is disclosed by the DuPont reference. The DuPont reference discloses what was known of the properties HFA-152a propellant possessed and applicant have not provided any evidence to the contrary. 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. Specifically, as DuPont disclose that HFA-152a has 99.9% purity and includes low level (ppm) water as an impurity (page 5), this amount of low moisture/water content would inherently be present in the propellant as it would not be possible to have a propellant with zero amount of moisture present. This is why DuPont also discloses low level of water in the propellant as an impurity where the propellant has 99.9% purity. Therefore, absence any show of evidence that not all HFA-152a propellant had the properties disclosed by Dupont, Applicant’s arguments are not found persuasive. Additionally, as discussed supra, Malhotra teaches that tiotropium is an extremely moisture sensitive drug and formulations containing tiotropium undergo hydrolytic degradation which results in an unstable formulation (para 0010). Malhotra and Noakes references already teach the 1,1-difluoroethane propellant and the DuPont reference teaches that the HFA-152a (1,1-difluoroethane) propellant include low level (ppm) of water (pg. 5 and pg. 24). It would have been obvious to one skilled in the art ensure that low level of water content (impurity) is contained in the formulation because tiotropium is a moisture sensitive drug and since DuPont already teaches the water content in HFA-152a propellant is low level (ppm) of water, one skilled in the art would have been motivated to ensure that the water content is kept low, such as in the amount recited in the instant claims.
Applicant also argued that Watson teaches levels of oxygen in water are typically no more than 10 ppm but Watson does not teach any oxygen content in a propellant. It was argued that the amount of dissolved oxygen based on the total weight of the composition will be in ppb level. Applicant argued the cited references do not teach the specific amount of oxygen as claimed.
In response, as discussed supra, Amighi discloses that tiotropium is oxidation sensitive wherein tiotropium undergoes chemical degradation due oxidation. Thus, it would have been obvious to one skilled in the art to ensure that the oxygen content in the composition is kept low (such as less than 1000 ppm as recited in instant claims) to avoid chemical degradation of tiotropium due to oxidation. The prior art recognizes that oxidation sensitive drug (e.g., tiotropium) undergoes chemical degradation due oxidation and absence any evidence of criticality of the specific claimed amount of oxygen content present, it would have been obvious to one skilled in the art to have only a low amount of oxygen present and determine an amount which would be least detrimental to the oxidation sensitive drug.
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 1, 6-12, 14-18, 20 and 22-26 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 Banholzer et al. (US 6,777,423 B2; Aug. 17, 2004).
The ‘710 application in claim 1 recites a pharmaceutical composition comprising beclomethasone dipropionate and formoterol fumarate dehydrate as the drug component and 1,1- difluoroethane as the propellant component. ‘710 recite the drug component additionally comprises long acting muscarinic antagonists including tiotropium. ‘710 recites the composition contains less than 500 ppm of water and less than 1000 ppm of oxygen which reads on instant claims. ‘710 recite that at least 90, 95 and 99 weight % of the propellant component is 1,1-difluoroethane. ‘710 recites propellant component contains from 0.5 to 10 ppm of unsaturated impurities. ‘710 recite the composition is free of a polar excipient. ‘710 recites the composition is free of acid stabilizers and perforated microstructures. ‘710 recites a metered dose inhaler fitted with a sealed and pressurized aerosol container that contains a pharmaceutical composition.
The ‘710 application recites the composition comprises tiotropium, however, it does not specifically teach monohydrate bromide salt form of tiotropium as recited in instant claim 1. However, this deficiency is cured by Banholzer.
Banholzer teaches crystalline tiotropium bromide monohydrate, process for the preparation thereof, pharmaceutical compositions thereof, and their use (Abstract). The reference discloses that tiotropium bromide is administered by use of inhalable aerosol which contain propellant such as HFA-134a or HFA-227. Banholzer teaches that the correct manufacture of these compositions is based on various parameters and requirements which include pharmaceutically active substance used for preparing the composition should be as pure as possible and its stability in long term storage must be guaranteed under various environmental conditions (Col. 1, line 43 to Col. 2 line 63). It further teaches that monohydrate of tiotropium bromide, which can be obtained in crystalline form by choosing specific reaction conditions, meets these requirements (Col. 3 line 7-13).
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 ‘710 to incorporate the teachings of Banholzer and incorporate monohydrate bromide salt form of tiotropium. One would have been motivated to do so because, as discussed above, Banholzer teaches that monohydrate of tiotropium bromide meets the stringent requirements such as the pharmaceutically active substance having stability in long term storage under various conditions and therefore one would have been motivated to comprise the monohydrate bromide salt form of tiotropium.
Regarding claims 16-18, 20, and 23, the structure of the ‘710 application composition is the same as 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 recited in instant claims. Further, the same amount of tiotropium bromide monohydrate would necessarily be present in the composition after storage under the conditions recited in instant claims. Also, the composition when delivered would necessarily yield the same amount of fine particle fraction of the tiotropium bromide monohydrate after storage under the conditions recited in 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.
This is a provisional nonstatutory double patenting rejection.
Claims 1, 6-12, 14-18, 20 and 22-26 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 4, 7-8, 13-15, 24-26, 33 and 39-40 of copending Application No. 16/334,156 (USPGPUB No. 20190388436) in view of Banholzer et al. (US 6,777,423 B2; Aug. 17, 2004).
The ‘156 application in claim 1 recites a pharmaceutical composition comprising beclomethasone dipropionate and formoterol fumarate dihydrate as the drug component and 1,1- difluoroethane as the propellant component. Claims 7-8 of ‘156 recite the drug component additionally comprises long acting muscarinic antagonists including tiotropium. Claims 2-5 of ‘156 recite amounts of water and oxygen which read on instant claim 2-5. Claims 13 and 14 of ‘156 recite weight % of the propellant component that reads on weight % recited in instant claims. Claim 15 of ‘156 recites propellant component contains 0.5 to 10 ppm of unsaturated impurities. ‘156 recite the composition is free of a polar excipient. ‘156 recite the composition in the form of suspension. Claim 26 of ‘156 recites the composition is free of perforated microstructures and acid stabilizers. Claim 33 of ‘156 recites a metered dose inhaler fitted with a sealed and pressurized aerosol container containing the composition. Claim 39 of ‘156 recites the composition is adapted to deliver the compounds making up the drug component in the same proportions that they occur in the pharmaceutical composition.
The ‘156 application recites the composition comprises tiotropium, however, it does not specifically teach monohydrate bromide salt form of tiotropium as recited in instant claim 1. However, this deficiency is cured by Banholzer.
Banholzer teaches crystalline tiotropium bromide monohydrate, process for the preparation thereof, pharmaceutical compositions thereof, and their use (Abstract). The reference discloses that tiotropium bromide is administered by use of inhalable aerosol which contain propellant such as HFA-134a or HFA-227. Banholzer teaches that the correct manufacture of these compositions is based on various parameters and requirements which include pharmaceutically active substance used for preparing the composition should be as pure as possible and its stability in long term storage must be guaranteed under various environmental conditions (Col. 1, line 43 to Col. 2 line 63). It further teaches that monohydrate of tiotropium bromide, which can be obtained in crystalline form by choosing specific reaction conditions, meets these requirements (Col. 3 line 7-13).
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 Banholzer and incorporate monohydrate bromide salt form of tiotropium. One would have been motivated to do so because, as discussed above, Banholzer teaches that monohydrate of tiotropium bromide meets the stringent requirements such as the pharmaceutically active substance having stability in long term storage under various conditions and therefore one would have been motivated to comprise the monohydrate bromide salt form of tiotropium.
Regarding claims 16-18, 20, and 23, the structure of the ‘710 application composition is the same as 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 recited in instant claims. Further, the same amount of tiotropium bromide monohydrate would necessarily be present in the composition after storage under the conditions recited in instant claims. Also, the composition when delivered would necessarily yield the same amount of fine particle fraction of the tiotropium bromide monohydrate after storage under the conditions recited in 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.
This is a provisional nonstatutory double patenting rejection.
Claims 1, 6-12, 14-18, 20 and 22-26 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 28-43 of copending Application No. 16/582,964 (USPGPUB No. 20200016175) in view of Banholzer et al. (US 6,777,423 B2; Aug. 17, 2004).
The ‘964 application recites adding a propellant component comprising 1,1-difluoroethane to the pharmaceutical composition, wherein the composition comprises beclomethasone compound and is free of polar excipient. ‘964 further recite the composition comprises beclomethasone dipropionate, long acting beta-2 agonist such as formoterol fumarate dihydrate, and long acting muscarinic antagonist such as tiotropium. ‘964 recites the pharmaceutical composition’s water content is below 500 ppm. ‘964 recite weight % of the propellant component that reads on weight % recited in instant claims. ‘964 recites propellant component contains from 0.5 to 10 ppm of unsaturated impurities. ‘964 recites the composition is free of perforated microstructures and acid stabilizers. ‘964 recite the composition in the form of suspension.
The ‘964 application recites the composition comprises tiotropium, however, it does not specifically teach monohydrate bromide salt form of tiotropium as recited in instant claim 1. However, this deficiency is cured by Banholzer.
Banholzer teaches crystalline tiotropium bromide monohydrate, process for the preparation thereof, pharmaceutical compositions thereof, and their use (Abstract). The reference discloses that tiotropium bromide is administered by use of inhalable aerosol which contain propellant such as HFA-134a or HFA-227. Banholzer teaches that the correct manufacture of these compositions is based on various parameters and requirements which include pharmaceutically active substance used for preparing the composition should be as pure as possible and its stability in long term storage must be guaranteed under various environmental conditions (Col. 1, line 43 to Col. 2 line 63). It further teaches that monohydrate of tiotropium bromide, which can be obtained in crystalline form by choosing specific reaction conditions, meets these requirements (Col. 3 line 7-13).
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 ‘964 to incorporate the teachings of Banholzer and incorporate monohydrate bromide salt form of tiotropium. One would have been motivated to do so because, as discussed above, Banholzer teaches that monohydrate of tiotropium bromide meets the stringent requirements such as the pharmaceutically active substance having stability in long term storage under various conditions and therefore one would have been motivated to comprise the monohydrate bromide salt form of tiotropium.
Regarding claims 16-18, 20, and 23, the structure of the ‘710 application composition is the same as 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 recited in instant claims. Further, the same amount of tiotropium bromide monohydrate would necessarily be present in the composition after storage under the conditions recited in instant claims. Also, the composition when delivered would necessarily yield the same amount of fine particle fraction of the tiotropium bromide monohydrate after storage under the conditions recited in 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.
This is a provisional nonstatutory double patenting rejection.
Claims 1, 6-12, 14-18, 20 and 22-26 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of U.S. Patent No. 11826349B2 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 in the amount (claim 2) recited in instant claims. ‘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 and composition optionally comprises ethanol but does not require it. ‘349 recites the composition is free of perforated microstructures and other components (claim 11). ‘349 also teach the composition in the form of suspension, solution and a metered dose inhaler (claim 1-2, 16). Composition is free of polar excipients.
‘349 does not teach wherein the composition comprises tiotropium bromide monohydrate and beclomethasone as the corticosteroid drug component. However, this deficiency is cured by Gaetano.
Gaetano teaches metered dose inhaler formulations wherein the formulations can comprise anticholinergic atropine-like derivatives which include ipratropium bromide, oxitropium bromide, tiotropium bromide and glycopyrronium bromide (i.e., salt of glycopyrrolate) and inhaled corticosteroid which include beclomethasone and budesonide (see Page 7, line 11-25). Further, the reference teaches that long acting beta agonist such as formoterol and antimuscarinic agents (tiotropium bromide) in combination with inhaled corticosteroids (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 include the antimuscarinic agent tiotropium bromide and beclomethasone as the corticosteroid in the formulation because the combination of the different classes of these drugs was known to be beneficial in preventing or treating disease.
Regarding claims 16-18, 20, and 23, the structure of the ‘349 patent composition is the same as 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 recited in instant claims. Further, the same amount of tiotropium bromide monohydrate would necessarily be present in the composition after storage under the conditions recited in instant claims. Also, the composition when delivered would necessarily yield the same amount of fine particle fraction of the tiotropium bromide monohydrate after storage under the conditions recited in 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 1, 6-12, 14-18, 20 and 22-26 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).
The ‘348 patent 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 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) and composition comprises optionally comprises ethanol (claim 10). ‘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). Composition is free of polar excipients.
‘348 does not teach wherein the composition comprises tiotropium bromide. However, this deficiency is cured by Gaetano.
Gaetano teaches metered dose inhaler formulations wherein the formulations 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 (tiotropium bromide) in combination with inhaled corticosteroids (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 include the antimuscarinic agent tiotropium bromide along with beclomethasone and formoterol in the formulation because the combination of the different classes of these drugs was known to be beneficial in preventing or treating disease.
Regarding claims 16-18, 20, and 23, the structure of the ‘348 composition is the same as 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 recited in instant claims. Further, the same amount of tiotropium bromide monohydrate would necessarily be present in the composition after storage under the conditions recited in instant claims. Also, the composition when delivered would necessarily yield the same amount of fine particle fraction of the tiotropium bromide monohydrate after storage under the conditions recited in 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 1, 6-18, 20 and 22-26 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-21 of U.S. Patent No. 11642330 B2 in view of Gaetano (WO 2007/121913 A2; Nov. 1, 2007).
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 (claims 4-7). ‘330 recites the composition can comprises ethanol but is not required, thus the composition can be free of polar excipient. ‘330 also teach the composition in the form of suspension, solution and a metered dose inhaler (claim 17, 19, 20). ‘330 claims the composition comprising surfactant such as polyethylene glycol surfactants (claim 11). ‘330 does not require acid stabilizers or perforated microstructures.
‘330 does not teach wherein the composition comprises tiotropium bromide monohydrate and beclomethasone as the corticosteroid drug component. However, this deficiency is cured by Gaetano.
Gaetano teaches metered dose inhaler formulations wherein the formulations 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 (tiotropium bromide) in combination with inhaled corticosteroids (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 include the antimuscarinic agent tiotropium bromide and beclomethasone as the corticosteroid in the formulation because the combination of the different classes of these drugs was known to be beneficial in preventing or treating disease.
Regarding claims 16-18, 20, and 23, the structure of the ‘330 patent composition is the same as 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 recited in instant claims. Further, the same amount of tiotropium bromide monohydrate would necessarily be present in the composition after storage under the conditions recited in instant claims. Also, the composition when delivered would necessarily yield the same amount of fine particle fraction of the tiotropium bromide monohydrate after storage under the conditions recited in 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 1, 6-18, 20 and 22-26 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).
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.
Examined claims are drawn to a composition, composition comprising tiotropium, 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 tiotropium, 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 such as tiotropium 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 1, 6-18, 20 and 22-26 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).
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.
Examined claims are drawn to a composition, composition comprising tiotropoium, 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 tiotropium, 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 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 such as tiotropium 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.
As the number of patents applied under obviousness type double patenting is very large, they are rejected collectively and based on similar analysis as stated above.
Claims 1, 6-18, 20 and 22-26 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).
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.
Examined claims are drawn to a composition, composition comprising tiotropium, 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 tiotropium, 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 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 such as tiotropium 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.
Claims 1, 6-18, 20 and 22-26 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).
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.
Examined claims are drawn to a composition, composition comprising tiotropium, 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 tiotropium, beclomethasone and formoterol, while reference claims require other active agents. This however is obvious in view of Gaetano and Keller 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 such as tiotropium 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 1, 6-18, 20 and 22-26 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.
Examined claims are drawn to a composition, composition comprising tiotropium, 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 tiotropium, 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 such as tiotropium 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 and tiotropium.
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 (e.g., tiotropium) 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 tiotropium, beclomethasone and formoterol, while reference claims require other active agents.
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.
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