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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 6/15/2026 has been entered.
Status of Action/Claims
Receipt of Remarks filed on 6/15/2026 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Rejection(s) not reiterated from the previous Office Action are hereby withdrawn.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Withdrawn Rejections/Objections
Applicant’s argument regarding the 103 rejections have been fully considered and are persuasive. The 103 rejections have been withdrawn because the prior art does not teach or render obvious the composition contains dissolved oxygen and water in the amounts recited in the instant claims.
New/Maintained Claim Rejection(s)
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 of U.S. Patent No. 11,690,823; 11,179,366; 11,077,076; 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 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
Regarding the double patenting rejections over 16582710, 16334156, 16582964 applicant argued the cited references fail to teach any modification to replace beclomethasone and formoterol with tiotropium.
In response, as discussed supra, ‘710, ‘156, 964 already teaches beclomethasone, formoterol and tiotropium. ‘710, ‘156, 964 do not teach monohydrate bromide salt form of tiotropium and Banholzer provides the motivation to include this salt form of tiotropium. The instant claims recite the drug comprises which allows for additional drug components and the instant claims themselves further recite including formoterol and beclomethasone. Thus, there is not modification needed to replace beclomethasone and formoterol with tiotropium.
Regarding US11,826,349 and 11,826,348, Applicant argued that these references teach glycopyrrolate, budesonide and formoterol as 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.
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 rejection over ‘330 patent has been withdrawn since the ‘330 patent does not teach water and dissolved oxygen.
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 appear to argue that a double patenting rejection of an instant claim should be over a specific single reference claim and not over all the claims. Applicant pointed to MPEP 804 II.B.2.
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.
Further, regarding the argument that a double patenting rejection of an instant claim should be over a specific single reference claim and not over all the claims, the examiner argues that no where in the MPEP is it stated and required that an instant claim should be over a specific single reference claim. For example, claim A can be rejected over claims A and B (e.g. B depends from A) when the limitations of claim A are recited in the combined claims A and B. For example, in the double patenting rejections above, the instant claims are rejected over claims of US 11,690,823 where ‘823 recites claims 1-20 and claims 2-20 depend from claim 1. Thus, limitations of the instant claims taught in either claim 1 or any dependent claim 2-20 of ‘823 would constitute a proper rejection because the MPEP does not require that all the limitations of one instant claims should be taught in a single reference claim. Therefore, applicant’s arguments regarding the grouping together of reference claims are not found persuasive at this time.
Conclusion
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/ALI S SAEED/Examiner, Art Unit 1616
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