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 the Application
Claims 22-41 are pending and are examined herein.
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 22-31, 33-38, 40-41 are rejected under the judicially created doctrine of obviousness-type double patenting as being unpatentable over claims 1 and 46 of U.S. Patent No. 9,499,553 in view of Ohtani et al. (WO 2014142273, of record) and Dalvi et al. (WO 2019/060604).
Although the conflicting claims are not identical, they are not patentably distinct from each other because both sets of claims recite 7-[[2,3-difluoro-4-[2-[-2-methoxyethyl(methyl)amino]-ethoxy]phenyl]methyl]-10-hydroxy-6-methyl-8-oxo-N-[4-(trifluoromethyl)-2-[6-(trifluoromethyl)pyrimidin-4-yl]phenyl]-6,7-diazaspiro[4.5]dec-9-ene-9-carboxamide. However, the referenced claims fail to disclose a disintegrant, a lubricant, an excipient, p-toluenesulfonate salt, and a volume-based particle size.
Ohtake et al. teach a method for preventing or treating a disease, such as hyperphosphatemia (claim 29), by administering a compound of formula I (claim 1). A preferred compound of formula I is 7-[[2,3-difluoro-4-[2-[-2-methoxyethyl(methyl)amino]-ethoxy]phenyl]methyl]-10-hydroxy-6-methyl-8-oxo-N-[4-(trifluoromethyl)-2-[6-(trifluoromethyl)pyrimidin-4-yl]phenyl]-6,7-diazaspiro[4.5]dec-9-ene-9-carboxamide (same structure as the claimed compound of formula I) (claim 46) or a salt thereof (col. 88, lines 40-48). The compositions may be produced by a well-known method using additives such as excipients, lubricants, and disintegrants, such as croscarmellose sodium (col. 91, lines 8-26). The compositions may be administered as a powder via inhalation (col. 90, lines 61-66).
It would have been prima facie obvious to a person of ordinary skill in the art, prior to the effective filing date of the claimed invention, to have formulated a composition comprising 7-[[2,3-difluoro-4-[2-[-2-methoxyethyl(methyl)amino]-ethoxy]phenyl]methyl]-10-hydroxy-6-methyl-8-oxo-N-[4-(trifluoromethyl)-2-[6-(trifluoromethyl)pyrimidin-4-yl]phenyl]-6,7-diazaspiro[4.5]dec-9-ene-9-carboxamide (same structure as the claimed compound of formula I) (claim 46) or a salt thereof with 12 wt% or more for the disintegrant, 5.3 wt% or more for the lubricant, and 25 wt% or more of the excipient.
A person of ordinary skill in the art would have been motivated to formulate a composition comprising 7-[[2,3-difluoro-4-[2-[-2-methoxyethyl(methyl)amino]-ethoxy]phenyl]methyl]-10-hydroxy-6-methyl-8-oxo-N-[4-(trifluoromethyl)-2-[6-(trifluoromethyl)pyrimidin-4-yl]phenyl]-6,7-diazaspiro[4.5]dec-9-ene-9-carboxamide (same structure as the claimed compound of formula I) (claim 46) or a salt thereof with 12 wt% or more for the disintegrant, 5.3 wt% or more for the lubricant, and 25 wt% or more of the excipient because Ohtake et al. already teaches that disintegrants, lubricants, and excipients can be formulated into the compositions. Furthermore, one of ordinary skill in the art would know how to optimize the amounts of disintegrants, lubricants, and excipients based on how much the breakdown into smaller fragments is desired, or how much reduced friction is desired, or how much help towards manufacturing and stability is desired.
Generally, mere optimization of ranges will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “When the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimal or workable ranges by routine experimentation. In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955); “The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.” In re Peterson, 315 F. 3d at 1330, 65 USPQ 2d at 1382; lt has been held that it is within the skills in the art to select optimal parameters, such as amounts of ingredients, in a composition in order to achieve a beneficial effect. In re Boesch, 205 USPQ 215 (CCPA 1980) MPEP 2114.04
Dalvi et al. teach an inhalable dry powder medicament (title and abstract). A dry powder medicament typically contains a micronized active ingredient with a mass median aerodynamic diameter of 1-10 µm. The size of the particle is able to penetrate into the lung on inhalation (page 3, lines 15-21). Preferably, the particle size is d10 = 0.4-1.0 µm, d50 = 1.0-3.0 µm, d90 = 2.5-9.0 µm (page 11, lines 20-21).
Therefore, it would have been prima facie obvious to a person of ordinary skill in the art, prior to the effective filing date of the claimed invention, to have modified the composition comprising 7-[[2,3-difluoro-4-[2-[-2-methoxyethyl(methyl)amino]-ethoxy]phenyl]methyl]-10-hydroxy-6-methyl-8-oxo-N-[4-(trifluoromethyl)-2-[6-(trifluoromethyl)pyrimidin-4-yl]phenyl]-6,7-diazaspiro[4.5]dec-9-ene-9-carboxamide, as taught by Ohtake et al., into a dry powder having a particle size of d10 = 0.4-1.0 µm, d50 = 1.0-3.0 µm, and d90 = 2.5-9.0 µm, as taught by Dalvi et al.
A person of ordinary skill in the art would have been motivated to formulate the composition comprising 7-[[2,3-difluoro-4-[2-[-2-methoxyethyl(methyl)amino]-ethoxy]phenyl]methyl]-10-hydroxy-6-methyl-8-oxo-N-[4-(trifluoromethyl)-2-[6-(trifluoromethyl)pyrimidin-4-yl]phenyl]-6,7-diazaspiro[4.5]dec-9-ene-9-carboxamide, as taught by Ohtake et al., into a dry powder having a particle size of d10 = 0.4-1.0 µm, d50 = 1.0-3.0 µm, and d90 = 2.5-9.0 µm because both Ohtake and Dalvi et al. teach an inhalable powder formulation, and Dalvi et al. teach the claimed particle size is well-suited for penetration into the lung on inhalation. Therefore, the skilled artisan would have had a reasonable expectation of success in formulating a composition comprising 7-[[2,3-difluoro-4-[2-[-2-methoxyethyl(methyl)amino]-ethoxy]phenyl]methyl]-10-hydroxy-6-methyl-8-oxo-N-[4-(trifluoromethyl)-2-[6-(trifluoromethyl)pyrimidin-4-yl]phenyl]-6,7-diazaspiro[4.5]dec-9-ene-9-carboxamide, as taught by Ohtake et al., into a dry powder having a particle size of d10 = 0.4-1.0 µm, d50 = 1.0-3.0 µm, and d90 = 2.5-9.0 µm.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 29 is rejected under 35 U.S.C. 112(d) or 112, fourth paragraph, for failing to limit a claim from which it depends. Claim 29 recites “wherein a content of the disintegrant is 12 wt% or more based on the total of the pharmaceutical composition,” which does not further limit claim 22, from which it depends.
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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
Claims 22, 25-31, 34-35 are rejected under 35 U.S.C. 103 as being unpatentable over Ohtake et al. (US Patent 9,499,553).
The instant claims are directed to a pharmaceutical composition and methods of making a pharmaceutical composition comprising a compound of formula I.
Ohtake et al. teach a method for preventing or treating a disease, such as hyperphosphatemia (claim 29), by administering a compound of formula I (claim 1). A preferred compound of formula I is 7-[[2,3-difluoro-4-[2-[-2-methoxyethyl(methyl)amino]-ethoxy]phenyl]methyl]-10-hydroxy-6-methyl-8-oxo-N-[4-(trifluoromethyl)-2-[6-(trifluoromethyl)pyrimidin-4-yl]phenyl]-6,7-diazaspiro[4.5]dec-9-ene-9-carboxamide (same structure as the claimed compound of formula I) (claim 46) or a salt thereof (col. 88, lines 40-48). The compositions may be produced by a well-known method using additives such as excipients, lubricants, and disintegrants, such as croscarmellose sodium (col. 91, lines 8-26). The compositions may be administered as a powder via inhalation (col. 90, lines 61-66).
However, Ohtake et al. fail to disclose 12 wt% or more for the disintegrant, 5.3 wt% or more for the lubricant, and 25 wt% or more of the excipient.
It would have been prima facie obvious to a person of ordinary skill in the art, prior to the effective filing date of the claimed invention, to have formulated a composition comprising 7-[[2,3-difluoro-4-[2-[-2-methoxyethyl(methyl)amino]-ethoxy]phenyl]methyl]-10-hydroxy-6-methyl-8-oxo-N-[4-(trifluoromethyl)-2-[6-(trifluoromethyl)pyrimidin-4-yl]phenyl]-6,7-diazaspiro[4.5]dec-9-ene-9-carboxamide (same structure as the claimed compound of formula I) (claim 46) or a salt thereof with 12 wt% or more for the disintegrant, 5.3 wt% or more for the lubricant, and 25 wt% or more of the excipient.
A person of ordinary skill in the art would have been motivated to formulate a composition comprising 7-[[2,3-difluoro-4-[2-[-2-methoxyethyl(methyl)amino]-ethoxy]phenyl]methyl]-10-hydroxy-6-methyl-8-oxo-N-[4-(trifluoromethyl)-2-[6-(trifluoromethyl)pyrimidin-4-yl]phenyl]-6,7-diazaspiro[4.5]dec-9-ene-9-carboxamide (same structure as the claimed compound of formula I) (claim 46) or a salt thereof with 12 wt% or more for the disintegrant, 5.3 wt% or more for the lubricant, and 25 wt% or more of the excipient because Ohtake et al. already teaches that disintegrants, lubricants, and excipients can be formulated into the compositions. Furthermore, one of ordinary skill in the art would know how to optimize the amounts of disintegrants, lubricants, and excipients based on how much the breakdown into smaller fragments is desired, or how much reduced friction is desired, or how much help towards manufacturing and stability is desired.
Generally, mere optimization of ranges will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “When the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimal or workable ranges by routine experimentation. In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955); “The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.” In re Peterson, 315 F. 3d at 1330, 65 USPQ 2d at 1382; lt has been held that it is within the skills in the art to select optimal parameters, such as amounts of ingredients, in a composition in order to achieve a beneficial effect. In re Boesch, 205 USPQ 215 (CCPA 1980) MPEP 2114.04
Claims 23-24, 33, 36-38, 40-41 are rejected under 35 U.S.C. 103 as being unpatentable over Ohtake et al. (US Patent 9,499,553), as applied to claims 22, 25-31, 34-35, in view of Dalvi et al. (WO 2019/060604).
The instant claims are directed to a pharmaceutical composition and methods of making a pharmaceutical composition comprising a compound of formula I.
Ohtake et al. teach as discussed above, however, fail to disclose a volume-based particle size.
Dalvi et al. teach an inhalable dry powder medicament (title and abstract). A dry powder medicament typically contains a micronized active ingredient with a mass median aerodynamic diameter of 1-10 µm. The size of the particle is able to penetrate into the lung on inhalation (page 3, lines 15-21). Preferably, the particle size is d10 = 0.4-1.0 µm, d50 = 1.0-3.0 µm, d90 = 2.5-9.0 µm (page 11, lines 20-21).
Therefore, it would have been prima facie obvious to a person of ordinary skill in the art, prior to the effective filing date of the claimed invention, to have modified the composition comprising 7-[[2,3-difluoro-4-[2-[-2-methoxyethyl(methyl)amino]-ethoxy]phenyl]methyl]-10-hydroxy-6-methyl-8-oxo-N-[4-(trifluoromethyl)-2-[6-(trifluoromethyl)pyrimidin-4-yl]phenyl]-6,7-diazaspiro[4.5]dec-9-ene-9-carboxamide, as taught by Ohtake et al., into a dry powder having a particle size of d10 = 0.4-1.0 µm, d50 = 1.0-3.0 µm, and d90 = 2.5-9.0 µm, as taught by Dalvi et al.
A person of ordinary skill in the art would have been motivated to formulate the composition comprising 7-[[2,3-difluoro-4-[2-[-2-methoxyethyl(methyl)amino]-ethoxy]phenyl]methyl]-10-hydroxy-6-methyl-8-oxo-N-[4-(trifluoromethyl)-2-[6-(trifluoromethyl)pyrimidin-4-yl]phenyl]-6,7-diazaspiro[4.5]dec-9-ene-9-carboxamide, as taught by Ohtake et al., into a dry powder having a particle size of d10 = 0.4-1.0 µm, d50 = 1.0-3.0 µm, and d90 = 2.5-9.0 µm because both Ohtake and Dalvi et al. teach an inhalable powder formulation, and Dalvi et al. teach the claimed particle size is well-suited for penetration into the lung on inhalation. Therefore, the skilled artisan would have had a reasonable expectation of success in formulating a composition comprising 7-[[2,3-difluoro-4-[2-[-2-methoxyethyl(methyl)amino]-ethoxy]phenyl]methyl]-10-hydroxy-6-methyl-8-oxo-N-[4-(trifluoromethyl)-2-[6-(trifluoromethyl)pyrimidin-4-yl]phenyl]-6,7-diazaspiro[4.5]dec-9-ene-9-carboxamide, as taught by Ohtake et al., into a dry powder having a particle size of d10 = 0.4-1.0 µm, d50 = 1.0-3.0 µm, and d90 = 2.5-9.0 µm.
Claim Objections
Claims 32 and 39 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Conclusion
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/Yong S. Chong/Primary Examiner, Art Unit 1623