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 .
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 (i.e., changing from AIA to pre-AIA ) 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.
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.
Claim(s) 2, 5, 7, 12, 21-23, 25-27, 39-40, 46 is/are rejected under 35 U.S.C. 103 as being unpatentable over HUANG (HUANG et al., WO2021252586A1, 2021-12-16).
The reference Huang teaches “ A liquid, propellant-free pharmaceutical formulation comprising:
(a) glycopyrrolate and indacaterol maleate;
(b) a solvent;
(c) a pharmacologically acceptable solubilizing agent; and
(d) a pharmacologically acceptable preservative, wherein the pharmaceutical formulation has a pH ranging from about 2.0 to about 6.0” (reference claim 1).
The reference HUANG teaches the structures of glycopyrrolate and indacaterol maleate:
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The reference Huang teaches “The pharmaceutical formulation according to claim 1, wherein the solvent is a water substantially free of other solvents” (reference claim 4) and “The pharmaceutical formulation according to claim 1, wherein the solubilizing agent is selected from the group consisting of tween-80, poloxamer, polyoxy ethylated castor oil, polyethylene glycol, solutol HS 15, polyvinylpyrrolidone, cyclodextrin derivatives, sulfobutylether b-cyclodextrin, and combinations thereof”(reference claim 5).
The reference Huang teaches “The pharmaceutical formulation according to claim 1, wherein glycopyrrolate is present in an amount ranging from about 0.2 mg/100 ml to about 550 mg/100 ml”(reference claim 2) and “The pharmaceutical formulation according to claim 1, wherein the indacaterol maleate is present in an amount ranging from about 0.34 mg/100 ml to about 1000 mg/100 ml”(reference claim 3). "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955.)
The reference also teaches (table 1 page 17) example 1 wherein the glycopyrrolate = .71 mg/mL and indacaterol =1.61mg/mL, and the water is about 95 weight %.
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The reference also teaches “The pH is of the formulation is selected so as to assure suitable stability of the formulation. In one embodiment, the pH of the formulation ranges from about 2.0 to about 6.0. In one embodiment, the pH of the formulation ranges from about 3.0 to about 5.0. In one embodiment, the pH of the formulation ranges from about 3.0 to about 4.0” [0046].
This helps to teach claims 2, 5, 7, 21, 25-27.
The reference also teaches “In one embodiment, the formulations include sodium chloride. In one embodiment, the concentration of sodium chloride ranges from about 0.1 g/100 ml to about 0.9 g/100 ml. [0061] In one embodiment, the concentration of glycopyrrolate in the formulation for nebulization inhalation ranges from about 1 mcg/ml to about 100 mcg/ml”[0060]. The instant specification defines tonicity modifiers to include NaCl [0007].
This helps to teach claims 12.
The reference HUANG teaches “In one embodiment, the formulations according to the invention include an acid or a base, as a pH adjusting agent. Suitable pH adjusting agents include, but are not limited to, hydrochloric acid, citric acid or its buffer and/or the salts thereof”[0044]. This helps to teach claims 22-23.
The reference HUANG teaches “A method of treating asthma or COPD in a patient, comprising administering to the patient the pharmaceutical formulation according to claim 1”(reference claim 1).
This helps to teach claims 39-40.
The reference Huang teaches “The present invention relates to a propellant-free inhalable formulation of glycopyrrolate or a solvate thereof and indacaterol or a salt or solvate thereof dissolved in water, in conjunction with inactive ingredients, preferably for administration using a soft mist or nebulization inhalation device, and the propellant-free inhalable aerosols resulting therefrom” [0008].
This helps to teach claim 46.
The reference also teaches “One aspect of the present invention is to provide an aqueous pharmaceutical formulation containing glycopyrrolate and indacaterol as a solution, which meets the high standards required to achieve optimal nebulization of the formulation using the inhalers mentioned hereinbefore. The pharmaceutical formulation has a storage time of some years, preferably at least about one year and more preferably at least about three years”[0011].
The reference Huang does not teach a specific composition with all the required correct variables but requires picking and choosing from among several suggested variables(all claims).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant invention to have modified HUANG to produce the compositions, methods and kit of the instant invention because HUANG teaches a device for inhaling a composition comprising glycopyrrolate and indacaterol maleate (with example 1 giving amounts in the correct composition range and pH=3), with a solubilizing agent including poloxamer and NaCl for the purpose of treating COPD. One would have a reasonable expectation of success because these variables are all suggested alternatives for the same formula with the same purpose of treating COPD. One would be motivated to explore these alternatives to find the optimal nebulization of the formulation [0011] that has a reasonable stability. It must be remembered that “[w]hen a patent simply arranges old elements with each performing the same function it had been known to perform and yields no more than one would expect from such an arrangement, the combination is obvious”. KSR v. Teleflex, 127 S,Ct. 1727, 1740 (2007) (quoting Sakraida v. A.G. Pro, 425 U.S. 273, 282 (1976)). “[W]hen the question is whether a patent claiming the combination of elements of prior art is obvious”, the relevant question is “whether the improvement is more than the predictable use of prior art elements according to their established functions.” (Id.). Addressing the issue of obviousness, the Supreme Court noted that the analysis under 35 USC 103 “need not seek out precise teachings directed to the specific subject matter of the challenged claim, for a court can take account of the inferences and creative steps that a person of ordinary skill in the art would employ.” KSR v. Teleflex, 127 S.Ct. 1727, 1741 (2007). The Court emphasized that “[a] person of ordinary skill is… a person of ordinary creativity, not an automaton.” Id. at 1742.
Claim(s) 2-5, 7, 12, 14-16, 21-23, 25-29, 39-40 and 46 is/are rejected under 35 U.S.C. 103 as being unpatentable over ZHANG (ZHANG et al., WO 2021068961 A1, 2021-04-15).
The reference Zhang teaches “Measure 1000mL of water, add 0.699g of citric acid and 0.492g of sodium citrate, stir until completely dissolved, then add the prescribed amount of sodium chloride and stir until completely dissolved; add an appropriate amount of hydrochloric acid to adjust the pH to 4.00±0.05, then add 0.15g of indacaterol acetate or indacaterol and the prescribed amount of glycopyrronium bromide raw material, stir until completely dissolved, filter, and test the concentration separately” [0186] and “The experimental results show that indacaterol acetate or indacaterol can be combined with glycopyrronium bromide to prepare a compound inhalation solution”[0189]. The reference teaches “In one embodiment, each 1000 mL of the pharmaceutical composition comprises: 0.04 g to 0.23 g of indacaterol or a pharmaceutically acceptable salt thereof (calculated as indacaterol), 0.02 g to 0.2 g of glycopyrronium bromide, 0.04 g to 0.5 g of mometasone furoate, 3 g to 7 g of sodium chloride, a citrate-sodium citrate buffer pair obtained by reacting 0.5 g to 4 g of citric acid monohydrate and 0.1 g to 0.8 g of sodium hydroxide, a pH adjuster adjusted to 2.5 to 5.0 as needed, and water added to 1000 mL”[0038]. The instant specification defines tonicity modifiers to include NaCl [0007].
The reference Zhang teaches “In one embodiment, the pharmaceutical composition further comprises other excipients selected from at least one of solubilizers, osmotic pressure regulators, and buffer ion pairs” [0014] and “In one embodiment, the solubilizer is selected from at least one of polysorbate, polyethylene glycol castor oil, polyoxyethylene castor oil, and lecithin” [0015].
This helps to teach claims 2-5, 7, 12, 21-23, 25-27.
The reference Zhang teaches “In one embodiment, the osmotic pressure regulator is selected from at least one of sodium chloride or mannitol” [0016]. The phrase “at least one of” implies that more than one is also considered obvious. Paragraph [0191] teaches the use of about 3g per 1000mL of water of NaCl which is about 50mM and paragraph [0212] teaches 50 g or mannitol per 1000 ml of water which is about 274 mM.
This helps to teach claims 14-16.
The reference Zhang teaches “Experimental results show that indacaterol acetate and glycopyrronium bromide can be combined with different steroid hormones to prepare a ternary compound inhalation solution”[0205] and “Clinically, COPD treatment drugs mainly include long-acting β2-receptor agonists (LABA), long-acting anticholinergic drugs (LAMA), and corticosteroids”[029].
This helps to teach claim 28-29.
The reference Zhang teaches “As the world's first marketed LABA/LAMA drug, indacaterol glycopyrronium bromide can activate β2 receptors while blocking M3 receptors, exhibiting a strong synergistic effect. Compared with monotherapy, it can significantly improve lung function, bringing a better treatment option for COPD. However, this product is only available in one dosage form: inhaled powder. For some patients with severe COPD, due to their poor lung function, they may not be able to reach the required airflow for inhaling the powder, resulting in the drug not being effectively delivered to the lungs or the delivery dose being reduced, thus decreasing the drug's efficacy. With nebulized inhalation, patients do not need special training, especially those with severe COPD, who can inhale a sufficient dose of medication using normal breathing...To address the shortcomings of existing technologies, one objective of this invention is to provide an inhalation solution pharmaceutical composition containing indacaterol or its salts, wherein the drug concentration in the composition is sufficiently high to meet clinical requirements for the volume of the inhalation solution, and the contents are released in a mist form using pressure from a manual pump, ultrasonic spray, air compressor, or other means, and it is a formulation for pulmonary inhalation”[0005-0007].
This helps to teach claims 39-40 and 46.
The reference Zhang does not teach a specific composition with all the required correct variables but requires picking and choosing from among several suggested variables(all claims).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant invention to have modified Zhang to produce the compositions, methods and kit of the instant invention because Zhang teaches a device for inhaling a composition comprising glycopyrronium bromide and indacaterol acetate (with an example giving amounts in the correct composition range and pH=4), with a solubilizing agent including polysorbate and NaCl and mannitol as osmotic pressure regulators for the purpose of treating COPD. One would have a reasonable expectation of success because these variables are all suggested alternatives for the same formula with the same purpose of treating COPD. One would be motivated to explore these alternatives to find the optimal nebulization of the formulation that has a reasonable stability. It must be remembered that “[w]hen a patent simply arranges old elements with each performing the same function it had been known to perform and yields no more than one would expect from such an arrangement, the combination is obvious”. KSR v. Teleflex, 127 S,Ct. 1727, 1740 (2007) (quoting Sakraida v. A.G. Pro, 425 U.S. 273, 282 (1976)). “[W]hen the question is whether a patent claiming the combination of elements of prior art is obvious”, the relevant question is “whether the improvement is more than the predictable use of prior art elements according to their established functions.” (Id.). Addressing the issue of obviousness, the Supreme Court noted that the analysis under 35 USC 103 “need not seek out precise teachings directed to the specific subject matter of the challenged claim, for a court can take account of the inferences and creative steps that a person of ordinary skill in the art would employ.” KSR v. Teleflex, 127 S.Ct. 1727, 1741 (2007). The Court emphasized that “[a] person of ordinary skill is… a person of ordinary creativity, not an automaton.” Id. at 1742.
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 filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual 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/apply/applying-online/eterminal-disclaimer.
Claims 2-5, 7, 12, 14-16, 21-23, 25-29, 39-40 and 46 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-39 of U.S. Patent No. 12419883 B2 in view of ZHANG (ZHANG et al., WO 2021068961 A1, 2021-04-15).
The patent ‘883 claims:
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This helps to teach claims 2-5, 7, 12, 14-16, 21-23, 25-29, 39-40 and 46.
The patent ‘883 does not teach polyethylene glycol, a povidone, glycerin, propylene glycol, a polysorbate, and a poloxamer (all claims).
The reference Zhang teaches that all needed changes would be obvious as outlined in the 103 rejection (which is incorporated herein by reference).
It would have been prima facie obvious to one of ordinary skill in the art to have modified patent ‘883 with Zhang to produce the compositions, methods and kit of the instant invention because both patent ‘883 and Zhang teaches a device for inhaling a composition comprising glycopyrronium bromide and indacaterol, and NaCl for the purpose of treating COPD and so it would be obvious to include the other elements of Zhang such as a solubilizing agent including polysorbate. One would have a reasonable expectation of success because the compositions are so similar and one would be motivated to do so to help improve solubility. It must be remembered that “[w]hen a patent simply arranges old elements with each performing the same function it had been known to perform and yields no more than one would expect from such an arrangement, the combination is obvious”. KSR v. Teleflex, 127 S,Ct. 1727, 1740 (2007) (quoting Sakraida v. A.G. Pro, 425 U.S. 273, 282 (1976)). “[W]hen the question is whether a patent claiming the combination of elements of prior art is obvious”, the relevant question is “whether the improvement is more than the predictable use of prior art elements according to their established functions.” (Id.). Addressing the issue of obviousness, the Supreme Court noted that the analysis under 35 USC 103 “need not seek out precise teachings directed to the specific subject matter of the challenged claim, for a court can take account of the inferences and creative steps that a person of ordinary skill in the art would employ.” KSR v. Teleflex, 127 S.Ct. 1727, 1741 (2007). The Court emphasized that “[a] person of ordinary skill is… a person of ordinary creativity, not an automaton.” Id. at 1742.
Claims 2-5, 7, 12, 14-16, 21-23, 25-29, 39-40 and 46 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 11844793 B2 in view of ZHANG (ZHANG et al., WO 2021068961 A1, 2021-04-15).
The patent ‘793 claims:
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The abstract teaches “Aqueous formulations of indacaterol are disclosed. The formulations may find use in the treatment of respiratory disorders, inflammatory disorders, or obstructive airway diseases. Methods of using the formulations and kits comprising the formulations are also encompassed by the disclosure”. A compound claim can be used to reject a method claim if the utility is disclosed in the specification. See Sun Pharmaceutical Industries v. Eli Lilly and Co., 611 F. 3d 1381, 1385 (CAFC 2010). See also MPEP § 804(II)(B)(2)(a).
This helps to teach claims 2-5, 7, 12, 14-16, 21-23, 25-29, 39-40 and 46.
The patent ‘793 does not teach polyethylene glycol, a povidone, glycerin, propylene glycol, a polysorbate, and a poloxamer (all claims) or the concentration of claim 16, or the methods of claims 39-40.
The reference Zhang teaches that all needed changes would be obvious as outlined in the 103 rejection (which is incorporated herein by reference).
It would have been prima facie obvious to one of ordinary skill in the art to have modified patent ‘793 with Zhang to produce the compositions, methods and kit of the instant invention because both patent ‘793 and Zhang teaches a device for inhaling a composition comprising glycopyrronium bromide and indacaterol, and NaCl for the purpose of treating COPD and so it would be obvious to include the other elements of Zhang such as a solubilizing agent including polysorbate. One would have a reasonable expectation of success because the compositions are so similar and one would be motivated to do so to help improve solubility. It must be remembered that “[w]hen a patent simply arranges old elements with each performing the same function it had been known to perform and yields no more than one would expect from such an arrangement, the combination is obvious”. KSR v. Teleflex, 127 S,Ct. 1727, 1740 (2007) (quoting Sakraida v. A.G. Pro, 425 U.S. 273, 282 (1976)). “[W]hen the question is whether a patent claiming the combination of elements of prior art is obvious”, the relevant question is “whether the improvement is more than the predictable use of prior art elements according to their established functions.” (Id.). Addressing the issue of obviousness, the Supreme Court noted that the analysis under 35 USC 103 “need not seek out precise teachings directed to the specific subject matter of the challenged claim, for a court can take account of the inferences and creative steps that a person of ordinary skill in the art would employ.” KSR v. Teleflex, 127 S.Ct. 1727, 1741 (2007). The Court emphasized that “[a] person of ordinary skill is… a person of ordinary creativity, not an automaton.” Id. at 1742.
Claims 2-5, 7, 12, 14-16, 21-23, 25-29, 39-40 and 46 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 21-40 of copending Application No. 19/315,294 and over claims 1-3, 9, 15, 29-38, 59-60, 64-65 of copending Application No. 19/470,557 in view of ZHANG (ZHANG et al., WO 2021068961 A1, 2021-04-15).
The application ‘294 claims:
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This is a provisional nonstatutory double patenting rejection.
The abstract teaches:
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A compound claim can be used to reject a method claim if the utility is disclosed in the specification. See Sun Pharmaceutical Industries v. Eli Lilly and Co., 611 F. 3d 1381, 1385 (CAFC 2010). See also MPEP § 804(II)(B)(2)(a).
This helps to teach claims 2-5, 7, 12, 14-16, 21-23, 25-29, 39-40 and 46.
The application ‘557 claims:
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The applications ‘294 and ‘557 do not teach polyethylene glycol, a povidone, glycerin, propylene glycol, a polysorbate, and a poloxamer (all claims) or the concentration of claim 16, or the composition of claims 14-16 or 25-29 or the methods of claims 39-40.
The reference Zhang teaches that all needed changes would be obvious as outlined in the 103 rejection (which is incorporated herein by reference).
It would have been prima facie obvious to one of ordinary skill in the art to have modified application ‘294 and ‘557 with Zhang to produce the compositions, methods and kit of the instant invention because both application ‘294 and Zhang teaches a device for inhaling a composition comprising glycopyrronium bromide and indacaterol, and NaCl for the purpose of treating COPD and so it would be obvious to include the other elements of Zhang such as a solubilizing agent including polysorbate. One would have a reasonable expectation of success because the compositions are so similar and one would be motivated to do so to help improve solubility. It must be remembered that “[w]hen a patent simply arranges old elements with each performing the same function it had been known to perform and yields no more than one would expect from such an arrangement, the combination is obvious”. KSR v. Teleflex, 127 S,Ct. 1727, 1740 (2007) (quoting Sakraida v. A.G. Pro, 425 U.S. 273, 282 (1976)). “[W]hen the question is whether a patent claiming the combination of elements of prior art is obvious”, the relevant question is “whether the improvement is more than the predictable use of prior art elements according to their established functions.” (Id.). Addressing the issue of obviousness, the Supreme Court noted that the analysis under 35 USC 103 “need not seek out precise teachings directed to the specific subject matter of the challenged claim, for a court can take account of the inferences and creative steps that a person of ordinary skill in the art would employ.” KSR v. Teleflex, 127 S.Ct. 1727, 1741 (2007). The Court emphasized that “[a] person of ordinary skill is… a person of ordinary creativity, not an automaton.” Id. at 1742.
Conclusion
Claims 2-5, 7, 12, 14-16, 21-23, 25-29, 39-40 and 46 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALISON AZAR HASTINGS whose telephone number is (703)756-4584. The examiner can normally be reached Mon-Thurs 7:30am-5pm EST Friday 7:30-4pm EST (every other Friday off).
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/A.A.H./ Examiner, Art Unit 1627
/Kortney L. Klinkel/ Supervisory Patent Examiner, Art Unit 1627