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 .
Receipt is acknowledged of Amendments, Remarks and an IDS filed on 08/21/25. Claims 1, 4 and 16 have been amended, claims 12 and 17 have ben canceled and no new claims have been added. Accordingly, claims 1-11, 13-16 and 18-20 remain pending and under examination on the merits.
Rejections and/or objections not reiterated from the previous Office Action are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set of rejections and/or objections presently being applied to the instant application.
Claim interpretation:
Independent Claims 1 and 16 are directed to a dry powder formulation. The recitation of “for use in a dry powder inhaler” in the preamble is an intended use limitation and not given patentable weight.
Claim Rejections - 35 USC § 103
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.
Applicant’s claims:
Claim 1 is directed to a powder formulation for use in a dry powder inhaler, the powder formulation comprising a carboxamide compound of formula I
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or a pharmaceutically acceptable salt thereof and an excipient, wherein the powder formulation comprises from about 0.25% by weight to about 10% by weight of the carboxamide compound of formula 1 based on a total weight of the powder formulation.
Claim 16 is directed to a powder formulation for use in a dry powder inhaler, the powder comprising a carboxamide compound of formula I
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or a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable excipient, and a long acting β2 adrenoceptor agonist, and optionally a corticosteroid, wherein the powder formulation comprises from about 0.25% by weight to about 10% by weight of the carboxamide compound of formula I and the carboxamide compound is a compound of formula II, and the β2 adrenoceptor agonist comprises salmeterol xinafoate, and the corticosteroid comprises fluticasone propionate.
Other claims add limitations such as specific excipients, other active agents, doses, particle size, etc.
Claims 1-11, 13-16 and 18-19 are rejected under 35 U.S.C. 103 as being unpatentable over Glossop et al (US 20100113409), Kim et al (US 20150157566) and Staniforth et al (US 20170216202).
Glossop et al teach hydrochloride salt of 5-[3-{3-hydroxyphenoxy)azetidin-1-yl]-5-methyl-2,2-diphenyl-hexanamide or derived form thereof and its use as a medicament (See abstract and claim 1).
It is disclosed that the compound is a cholinergic muscarinic agent is known for treating asthma and COPD (See [0002]-[003], [0018] and claim 9).
The said hydrochloride salt is particularly suitable for an administration by the inhalation route. In particular, the said hydrochloride salt can be formulated for an administration using a dry powder inhaler (See [0011]).
Glossop et al further teach that the said hydrochloride salt may be administered alone or in combination with other drugs and will generally be administered as a formulation in association with one or more pharmaceutically acceptable excipients (See [0021]).
Disclosed is the combination of the compounds of formula (I) with: glucocorticosteroids such as fluticasone propionate, β2 agonists including salmeterol, and their salts are further preferred (See [0090]).
Glossop et al also disclose a method making 5-3-(3-Hydroxy-phenoxy)-azetidin-1-yl-5-methyl 2,2-diphenyl-hexanoic acid amide hydrochloride,
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or
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(See [0104]-[0105] and [0118]).
It is disclosed that the said dry powder inhalers and aerosols deliver a metered dose or “puff” containing from 0.001 mg to 10 mg of the said hydrochloride salt (See [0035]). For administration to human patients, the total daily dose of the said hydrochloride salt is typically in the range 0.001 mg to 5000 mg (See [0044]).
Glossop et al further disclose that capsules, blisters and cartridges for use in an inhaler may be formulated to contain a powder mix of the said hydrochloride salt, a suitable powder base such as lactose or starch and a performance modifier such as l-leucine, mannitol, or magnesium stearate, preferably lactose monohydrate. Other suitable excipients include dextran, glucose, maltose, sorbitol, xylitol, fructose, sucrose and trehalose (See [0028], [0031], [0035] and [0042]).
It is further disclosed that two or more pharmaceutical compositions, at least one of which contains the said hydrochloride salt, may conveniently be combined in the form of a kit suitable for coadministration of the compositions. The said kit comprises two or more separate pharmaceutical compositions, at least one of which contains the hydrochloride salt, and means for separately retaining said compositions, such as a container, divided bottle, or divided foil packet. An example of such a kit is the familiar blister pack used for the packaging of tablets, capsules and the like (See [0041]-[0042]).
Glossop et al lack a disclosure on some particle specifics such as fine and coarse particle size, FPF values, the salt of salmeterol and its amounts. These are known in the art as taught by Kim et al and Staniforth et al.
Kim et al teach a dry powder for inhalation formulation comprising salmeterol xinafoate, fluticasone propionate and tiotropium bromide, as pharmaceutically active ingredients, and a carrier, and an inhalation formulation comprising same. The said dry powder inhalation formulation having good content uniformity and showing small changes in the aerodynamic size distribution in accordance with the flow rate changes can effectively deliver said pharmaceutically active ingredients to a target site upon administration, and thus can be useful in the prevention or treatment of respiratory diseases, particularly asthma and COPD (See abstract).
Kim et al disclose a dry powder for inhalation formulation comprising salmeterol xinafoate, fluticasone propionate, tiotropium bromide, and a carrier, having an average particle size in a range of 30 to 120 μm, preferably in a range of 55 to 65 μm (See [0016], [0034] and claims 1-2).
The said powder formulations comprising an excipient/carrier which may be glucose, arabinose, lactose, maltose, sucrose, starch, dextrin or dextran; sorbitol, mannitol, etc, and preferably lactose monohydrate (See [0030] and claim 4).
Kim et al further disclose that the said powder formulations may be filled into capsules or blister packages (See [0031]).
Disclosed is that in the said dry powder inhalation formulation, salmeterol xinafoate, fluticasone propionate and tiotropium bromide may be employed in amounts of 25 to 100 μg, 25 to 500 μg, and 5 to 50 μg, respectively, per dosage unit. However, employable amounts are not limited thereto, and may be adjusted depending on the various factors, e.g., the patient and disease condition being treated (See [0041]).
Staniforth et al teach a method of making a composition for inhalation which includes the step of mixing particles of additive material and active particles for delivery via a dry powder inhaler (See abstract).
It is disclosed that the said dry powder composition is suitable for use in a dry powder inhaler and may comprise or consist essentially of only the active particles, the additive particles and carrier particles. The said carrier particles may be lactose (See [0047]).
Advantageously, substantially all (by weight) of the carrier particles have a diameter which lies between 20 μm and 250 μm. Preferably at least 90% by weight of the carrier particles have a diameter between from 60 μm and 180 µm (See [0048]).
It is further disclosed that the said carrier particles are preferably present in an amount of at least 50%, more preferably 70%, advantageously 90% and most preferably 95% based on the combined weight of the particles of active substance, particles of additive material and the carrier particles. The said dry powder composition may preferably also includes small particles comprised of the same or another excipient material as the carrier particles having a particle size between 5 to 20 μm. Preferably the small excipient particles are present in an amount of from 1% to 40%, more preferably 5% to 20% based on the weight of the carrier particles (See [0049]-[0050]).
The active agents include salmeterol, fluticasone, etc, (See [0052[ and [0054]).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date to have combined the teachings of Staniforth et al and Kim et al with that of Glossop et al to arrive at the instant invention. It would have been obvious to do so because Glossop et al teach a dry powder formulation for inhalation comprising a compound of formula I or its hydrochloride salt and an excipient preferably lactose monohydrate. Glossop et al also disclose that other active agents including salmeterol and fluticasone may be added and that such formulations may be filled into a plurality of containers such as capsules or blisters. One of ordinary skill in the art is motivated to have looked in the art for dry powder specifics to prepare an effective formulation for delivery. These specifics are taught by Kim et al and Staniforth et al.
Kim et al, also directed to a dry powder formulation for inhalation comprising salmeterol xinafoate, fluticasone propionate and a third active agent, an anticholinergic agent and a carrier including lactose monohydrate and provide guidance on the amount of such active agents. Kim et al additionally provide guidance on the particle size. Staniforth et al is directed to a powder formulation comprising one or more active agents and a carrier including lactose and wherein the carrier particles being a mix of coarse particles and fine particles.
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 7-11, 13-16 and 18-20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 7-20 of copending Application No. 18/011,770 (US 20230225973) (Issued but not yet published). An obviousness-type double patenting rejection is appropriate because while the conflicting claims are not identical, the examined claims are not patentably distinct from the reference claims because the examined claims would have been obvious over the reference claims.
The examined claims are drawn to a powder formulation comprising an amount of compound 5-3-(3-Hydroxy-phenoxy)-azetidin-1-yl-5-methyl 2,2-diphenyl-hexanoic acid amide hydrochloride, in one or more pockets for inhalation to a subject.
The reference claims are similarly drawn to medicament for inhalation comprising two or more layers of powders each layer comprising an active agent and optionally an excipient, wherein one of the active agents is 5-3-(3-Hydroxy-phenoxy)-azetidin-1-yl-5-methyl 2,2-diphenyl-hexanoic acid amide hydrochloride. The powder is placed in a container comprising one or more pockets.
While the arrangement and/or order of limitations between the two sets of claims is slightly different, the two sets of claims are drawn to the same formulation placed in the same container.
Thus, the examined claims are not patentably distinguished from the reference claims.
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
Applicant's arguments filed 08/21/25 have been fully considered but they are not persuasive.
Applicant argues that claims 1 and 16 have been amended and that “The cited references do not disclose or make obvious these features. Regarding the Glossop reference, Glossop discloses the hydrochloride salt of 5-[3-{3- hydroxy phenoxy )azetidin-1-yl]-5-methy1-2,2-diphenyl-hexanamide or its derivative thereof. However, it does not disclose a specific percentage of the carboxamide compound as currently claimed. … Kim discloses a dry powder formulation for inhalation; however, Kim does not disclose Formula I. The Office emphasizes that Kim discloses salmeterol xinafoate, and fluticasone propionate. However, Applicant notes that Kim instead replaces Formula I with a different active that is tiotropium bromide. Even if there is some mention of similar actives, there is clearly no mention of Formula I or the percentage of the carboxamide of Formula I in the formulation as currently claimed” (See Remarks, pages 8-9).
The arguments have been fully considered and found not persuasive. While Applicant’s statement regarding the elements not disclosed in each of Glossop and Kim references, the rejection has shown that the combination of the two references would have rendered the claimed formulations obvious (in further view of Staniforth).
Specifically, Applicant’s argument regarding Glossop not teaching the recited concentration of the carboxamide compound of formula I is not found persuasive because Glossop provides adequate teachings on the suitable amounts of the carboxamide compound of formula I. the difference is that Glossop discloses these amounts in terms of mg while claims recite the amounts in terms of percentages. Instant claims 1 and 16 recite a dry powder formulation comprising from 0.25 to 10% by weight of the said compound and a nominal dose of from 0.018 to 7 mg. Glossop teach a dry powder formulation comprising from 0.001 mg to 10 mg of the said hydrochloride salt of the compound or a total daily dose in the range 0.001 mg to 5000 mg. thus, Glossop’s dose of 0.01 to 10 mg meets the claimed dose of 0.018 to 7 mg. additionally, one of ordinary skill in the art is more than capable of determining the concentration of the compound in percentages based on the dosage amounts of Glossop.
The argument that Kim does not teach the claimed compound is also not convincing because as the rejection clearly stated, Kim was relied upon for teaching a dry powder composition comprising salmeterol xinafoate, fluticasone propionate and an anticholinergic compound similar to the claimed compound. Kim’s disclosure would motivate one of ordinary skill in the art to prepare formulations comprising a combination of different active agents with different mechanism of action to treat respiratory diseases more effectively than by a single compound. Kim also teaches a carrier including lactose monohydrate and provide guidance on the amount of such active agents and provide guidance on the particle size ranges. Thus, one of ordinary skill in the art is motivated to combine the teachings of Glossop and Kim and arrive at a dry powder composition that comprises an effective amount of a compound of formula I plus other active agents suitable for a combination with an anticholinergic agent with a reasonable expectation of success.
Regarding the teachings of Staniforth et al, Applicant argues that “Staniforth discloses methods of making a composition for inhalation; however, there is no method in Staniforth directed to making the carboxamide of Formula I. The Office alleges that Staniforth teaches salmeterol, fluticasone and certain carrier particles in the 1- 20% range” (See Remarks, page 9).
This argument is also not convincing. Staniforth et al’s disclosure is in an analogous art, that is making of a dry powder composition comprising one or more active agents and carriers. Staniforth et al was relied upon for its disclosure of the compound of formula I or its percentages. Rather Staniforth et al teach a dry powder composition wherein, effectively the carrier particles comprise both coarse and fine particles of lactose monohydrate. This teaching of Staniforth et al has been shown to provide additional advantages to a dry powder formulation, which one of ordinary skill in the art is more than motivated to incorporate into other formulations.
It is noted that if Glossop, Kim or Staniforth references taught all limitations of the claims, they each would be applied as an anticipatory reference. That is, in response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Arguments regarding the teachings of Nilsson et al (both references) are persuasive and as such the rejections relying on these references were withdrawn.
Regarding the rejection of claims under grounds of nonstatutory double patenting over Co-pending Application No. 18/011,770, Applicant argues that the said rejection should be considered in view of the new amendments. Applicant also requests that the double patenting rejection be held in abeyance until the claims are otherwise allowable (See Remarks, page 10).
The amended claims have been considered and the rejection has been maintained. It is also noted that the claims in the co-pending Application have since been considered allowable, but not yet issued.
Claims 1-11, 13-16 and 18-20 are rejected.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Mina Haghighatian whose telephone number is (571)272-0615. The examiner can normally be reached M-F, 7-5 EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sue X. Liu can be reached on 571-272-5539. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Mina Haghighatian/
Mina Haghighatian
Primary Examiner
Art Unit 1616