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 .
Priority
This application is a CON of U.S. Application No. 15/514,155, filed March 24, 2017 which is 371 of PCT/JP2015/077015, filed September 25, 2015, and claims foreign priority to JP2014-195279, filed September 25, 2014.
Claim Status
Claims 1-11 are currently pending and subject to examination.
Claim Rejections - 35 USC § 103 – Previously Presented
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.
The rejection of claims 1-4, 10 and 11 under 35 U.S.C. 103 as being unpatentable over Hidaka et al. (U.S. Patent Application Publication No. 2008/0064681 A1; 2008) (of record, IDS cite no. 7) in view of Hitoshi et al. (JP 09-024085 A; 1997, citing to the English translation submitted in the record by Applicant on 11/19/19) (of record, IDS cite no. 24) and Kimura et al. (U.S. Patent Application No. 2013/0281529 A1; Published October 24, 2013) (of record, IDS cite no. 18) is maintained.
The rejection of claims 5-9 under 35 U.S.C. 103 as being unpatentable over Hidaka et al. (U.S. Patent Application Publication No. 2008/0064681 A1; 2008) in view of Hitoshi et al. (JP 09-024085 A; 1997, citing to the English translation submitted in the record by Applicant on 11/19/19) and Kimura et al. (U.S. Patent Application No. 2013/0281529 A1; Published October 24, 2013), as applied above to claims 1, 3-5, 10 and 11, further in view of Danielson et al. (U.S. Patent No. 6,602,447 B2; 2003) (of record, IDS cite no. 19) and Ammala et al. (‘Degradation Studies of Polyolefins Incorporating Transparent Nanoparticulate Zinc Oxide UV Stabilizers”, Journal of Nanoparticle Research, 2002; 4:167-174) (of record, IDS cito no. 61) is maintained.
Response to Arguments
The Applicant amended the claims to recite that the light blocking member is on the inner surface rather than the outer surface of the container and argues that there is no suggestion or motivation to coat an inner surface of the primary package (Remarks, p. 6-7). These arguments were fully considered but are not persuasive. It is prima facie obvious to rearrange parts present in the prior art device as this is an obvious matter of design choice:
C. Rearrangement of Parts
In re Japikse, 181 F.2d 1019, 86 USPQ 70 (CCPA 1950) (Claims to a hydraulic power press which read on the prior art except with regard to the position of the starting switch were held unpatentable because shifting the position of the starting switch would not have modified the operation of the device.); In re Kuhle, 526 F.2d 553, 188 USPQ 7 (CCPA 1975) (the particular placement of a contact in a conductivity measuring device was held to be an obvious matter of design choice).
MPEP 2144.04.VI.
An ordinary artisan is well aware that the placement of a film opaque to a particular wavelength of light is immaterial to the operability of the film.
The Applicant argues that one of ordinary skill in the art would not have expected that aqueous ripsudil would be unstable (Remarks, p. 7). These arguments were fully considered but are not persuasive.
Hidaka teaches ripasudil, a compound of formula:
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(Ex.1, p.4, para.[0043]).. One of ordinary skill in the art would reasonably expect this compound to be unstable in aqueous solution because Hitoshi et al. teaches that aqueous solutions of fasudil hydrochloride, an analog of ripasudil, a compound which has the structure ,
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have poor light stability as evidenced by browning of the solution after exposure to sunlight and about 3000 lux light of a fluorescent lamp (para.[0004]; para.[0008}). One of ordinary skill in the art would therefore consider it necessary to block containers comprising aqueous solutions of ripasudil from light.
The Applicant argues that the subject matter of the present claims is associated with unexpected improvements in the storage and stability of ripasudil (Remarks, p. 7-8). These arguments were fully considered but are not persuasive. Hitoshi et al. exemplifies the use of a vinyl coating film for glass containers of fasudil hydrochloride, wherein the film was wrapped around the barrel of the container, and demonstrates that such coatings were effective to fully block light with wavelengths of 200 to nearly 400 nm, noting that the solutions inside such film- wrapped containers were found to be stable without decomposition (para.[0018]-[0019]; Table 1, para.[0022]; para.[0025]; Figs.3-4). Figs. 3-4 clearly show that Hitoshi’s films are completely opaque to light at this wavelength.
The affidavit under 37 CFR 1.132 filed Nov. 28, 2025 is insufficient to overcome the rejection of claims 1-11 based upon 35 U.S.C. 103 as set forth in the last Office action because: the Applicant does not show a comparison with the closest prior art. The Applicant merely selected generic bottles from a pharmaceutical catalog and tested their ability to block light at a wavelength of 300-335 nm. The Applicant did not compare their invention to e.g. the light blocking films of Hitoshi. The Applicant does not show that their invention outperforms products that an ordinary artisan would reasonably expect to block light and stabilize compounds similar to ripasudil or fasudil.
Reiterated Rejection
Claims 1-4, 10 and 11 are rejected under 35 U.S.C. 103 as being unpatentable over Hidaka et al. (U.S. Patent Application Publication No. 2008/0064681 A1; 2008) (of record, IDS cite no. 7) in view of Hitoshi et al. (JP 09-024085 A; 1997, citing to the English translation submitted in the record by Applicant on 11/19/19) (of record, IDS cite no. 24) and Kimura et al. (U.S. Patent Application No. 2013/0281529 A1; Published October 24, 2013) (of record, IDS cite no. 18).
Claim 1 is directed towards:
A pharmaceutical preparation, comprising:
an aqueous composition comprising 0.05 to 5 w/v% ripasudil, or a salt thereof, or a solvate of ripasudil or the salt thereof, calculated as the free form, based on a total volume of the aqueous composition; and
a primary package containing the aqueous composition, wherein the primary package is capable of blocking ultraviolet light having a wavelength of 300 to 335 nm, and the primary package is a polypropylene or polyethylene container comprising a substance that prevents transmission of ultraviolet light having a wavelength of 300 to 335 nm or the primary package is a polypropylene or polyethylene container including a member comprising a substance that prevents transmission of ultraviolet light having a wavelength of 300 to 335 nm, wherein
50% or more of a total area of an inner surface of the primary package blocks ultraviolet light having a wavelength of 300 to 335 nm so that an average value of transmittance of the light is 10% or less, and
the average value of transmittance of light is obtained by measuring light transmittance of the primary package in air per 0.5 nm in the range of a wavelength of 300 to 335 nm using a spectrophotometer, and then calculating an average value of the measured light transmittance.
Hidaka et al. teaches compounds of formula (1), which has the chemical structure
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in which ring A represents a 5- to 11-membered cyclic amino group, which may be further substituted, and X is a halogen atom, or more specifically compounds of the narrower structure
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of formula (4) in which X is a halogen atom, in particular, bromine, chlorine or fluorine, which are effective to reduce intraocular pressure when administered to a glaucoma patient (abstract; p.1, para.[0007]-[0008]; p.2-3, para.[0025]; p.3, para.[0026]). Hidaka et al. teaches that the compound may also be in the form of a salt or a solvate, such as a hydrate (p.3, para.[0027]). Hidaka et al. teaches that the efficacy of the compounds to reduce intraocular pressure and thereby treat glaucoma renders them particularly useful when formulated as eye drops using a pharmaceutically acceptable carrier therefor (p.4, para.[0039]-[0040]). Hidaka et al. exemplifies synthesis of the compound “F7”, also known as (S)-hexahydro-1 -(4-fluoroisoquinoline-5-sulfonyl)-2-methyl-1H-1,4-diazepine dihydrochloride, which has the
chemical structure
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and corresponds to Hidaka’s compounds of formula (4), in which X is fluorine (Ex.1, p.4, para.[0043]). Hidaka et al. teaches the compound F7 as having inhibitory activity on Rho-kinase, as evidenced by the ICso value reported in Table 1 (p.13, para.[0115]). Hidaka et al. teaches the preparation of compound F7 into an eye drop formulation, obtained by dissolving 1.0 g of the compound in a phosphate buffer solution (which was prepared by dissolving 0.8 g of sodium dihydrogen phosphate and 0.5 g of sodium chloride in purified water to a final weight of 100 g, after which the pH was adjusted to 7.0 using sodium hydroxide), for administration to rabbits to determine the effect of the compound on intraocular pressure (Ex.2, p.13, para.[01 1 7]-[0119]). Hidaka et al. teaches that instillation of the F7-containing eye drop was effective to reduce intraocular pressure 1.9x more than control Rho-kinase inhibitor compound M, and that the period of time in which the intraocular pressure-reducing effect was demonstrated was also about 3 h longer than that of control compound M (p.13, para.[0120]-[0121]).
The F7 compound identified in Hidaka et al. corresponds to Applicant’s instantly claimed ripasudil (Specification, p.1, para.[0002]-[0003}).
Hidaka et al. differs from the instant claims only insofar as it does not explicitly teach the ripasudil eye drop is contained in a polypropylene or polyethylene container comprising a substance, or member comprising a substance, that prevents transmission of UV light with wavelength of 300-335 nm (claims 1, 17, 19), or the effect of improving photostability of ripasudil or preservation of ripasudil when contained in this manner (claims 17, 19).
Hitoshi et al. teaches that aqueous solutions of fasudil hydrochloride, a compound which has the
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structure , have poor light stability as evidenced by browning of the solution after exposure to sunlight and about 3000 lux light of a fluorescent lamp (para.[0004]; para.[0008}). Hitoshi et al. teaches that the use of containers that restrict penetration of light with wavelengths of 350 nm to no more than 10% is effective to prevent decomposition of fasudil hydrochloride up to 1,200,000 lux-hr (equivalent to continuous 400-h exposure to light of about 3000 lux) and stabilizes the aqueous solution (para.[0006]). Hitoshi et al. teaches that coating films made of polyvinyl chloride or polypropylene may be applied to containers, such as an ampoule, vial, or syringe, by twisting it around the container to provide 10% or less transmission of UV light with wavelength of 350 nm (para.[0011]). Hitoshi et al. exemplifies the use of a vinyl coating film for glass containers of fasudil hydrochloride, wherein the film was wrapped around the barrel of the container, and demonstrates that such coatings were effective to fully block light with wavelengths of 200 to nearly 400 nm, noting that the solutions inside such film- wrapped containers were found to be stable without decomposition (para.[0018]-[0019]; Table 1, para.[0022]; para.[0025]; Figs.3-4).
Kimura et al. teaches the use of thermoplastic resin containers, e.g., those made of polyethylene, polypropylene, polyethylene terephthalate, etc., for packaging eye drop preparations of latanoprost, a ocular hypotensive compound known to easily degrade in aqueous solution (p.1, para.[0008]; p.5, para.[0081]). Kimura et al. teaches that the thermoplastic resin preferably has a transparency that allows the contained solution and insoluble contaminants to be seen from the outside (p.5, para.[0081]). Kimura et al. teaches that polyethylene and polypropylene are generally preferred materials that provide flexibility and balance between moisture permeation (water vapor barrier) and adsorption of the active ingredients (p.5, para.[0081]). Kimura et al. teaches that the container should be suitable to contain a liquid and generally has a cylindrical shape, have a capacity suitable for a multi-dose container, and may be further covered with a shrinkable film after packaging the eye drop preparation (p.5, para.[0082]).
A person of ordinary skill in the art before the effective filing date of the claimed invention would have reasonably expected that the aqueous ripasudil eye drop of Hidaka et al. exhibited poor light stability and decomposition when exposed to UV light with wavelength of 350 nm, because Hitoshi et al. teaches that structurally similar compounds exhibiting a seven-membered nitrogen-containing heterocycle bonded with sulfonyl isoquinoline (such as fasudil) were known to have poor light stability and increased degradation in aqueous solution at such UV wavelengths. Such teachings raise the reasonable expectation of success that structurally similar ripasudil also exhibited this property of photosensitivity at such UV wavelengths given the high degree of structural similarity between the two compounds and, therefore, would have been similarly effectively stabilized by formulating such aqueous ripasudil composition into a container wrapped with Hitoshi’s light-blocking films that block light of wavelength between 200 to nearly 400 nm, in light of Hitoshi’s teachings demonstrating that aqueous fasudil hydrochloride solutions were effectively stabilized from UV decomposition when prepared in packaging wrapped with Hitoshi’s light-blocking films effective to block light of wavelength from 200 to about 400 nm.
Though Hitoshi et al. exemplifies the use of his light-blocking polyvinyl chloride film applied to the barrel of a glass container (not a polyethylene or polypropylene container as instantly claimed), a person of ordinary skill in the art before the effective filing date of the claimed invention would have had a reasonable expectation of success in employing a polyethylene or polypropylene eye drop container for packaging the aqueous ripasudil eye drop of Hidaka et al. because Kimura et al. teaches thermoplastic resin eye drop containers made of polyethylene or polypropylene for packaging unstable aqueous eye drop solutions of glaucoma-treating agents. The skilled artisan would have found it prima facie obvious to employ a polyethylene or polypropylene eye drop container to package the aqueous ripasudil eye drop of Hidaka et al. because Kimura et al. teaches that such thermoplastic resins were known to be flexible and balance moisture permeation and adsorption of the active ingredients into the plastic, while also exhibiting a transparency permitting the contents of the container to be visible from the outside. The ordinarily skilled artisan would have also found it prima facie obvious to employ a polyethylene or polypropylene eye drop container to package the aqueous ripasudil eye drop of Hidaka et al. with Hitoshi’s light-blocking film to block light of wavelengths between 200 to about 400 nm because Kimura et al. teaches that such thermoplastic resin eye drop containers were suitable for covering with a shrinkable film after packaging the eye drop preparation.
As established above, the prior art teachings of Hitoshi et al. and Kimura et al. provide reason to formulate the aqueous ripasudil eye drop preparation of Hidaka et al. into a polyethylene or polypropylene eye drop container to which Hitoshi’s light-blocking film that blocks UV light of wavelengths between 200 to about 400 nm has been applied (equivalent to Applicant’s instantly claimed “substance”) for the purpose of preventing UV light-induced degradation of the aqueous solution.
As this light-blocking range of 200 to nearly 400 nm clearly circumscribes Applicant’s instantly claimed range of 300-335 nm, Hitoshi’s light-blocking film clearly meets Applicant’s recited “substance that prevents transmission of [UV] light having a wavelength of 300 to 335 nm”. As stated in MPEP §2144.05, “In the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990) ...” [A] prior art reference that discloses a range encompassing a somewhat narrower range is sufficient to establish a prima facie case of obviousness.” In re Peterson, 315 F.3d 1325, 1330, 65 USPQ2d 1379, 1382-83 (Fed. Cir. 2003). See also In re Harris, 409 F.3d 1339, 74 USPQ2d 1951 (Fed. Cir. 2005).”
While the Applicant has amended the claims to recite that the film is on the inner surface of the container rather than the outer surface as in Hitoshi, such a rearrangement of parts does not impart patentability. It is prima facie obvious to rearrange parts (MPEP 2144.04.VI.C).
Therefore, claim 1 was prima facie obvious at the time of filing.
Similar rationale applies also to claim 3, as well as claim 4, which recites that the “polypropylene or polyethylene container” includes “a member comprising a substance that prevents transmission of [UV] light”. As there is no specificity in claim 5 defining the “member” as a distinct entity from the “substance” itself, then the same reasoning as applied to claim 4 applies also to claim 5.
In claim 2, Applicant requires that “the inside of the package is visible’.
As established above, Kimura et al. clearly teaches the use of a polyethylene or polypropylene eye drop container, in which the container exhibits a transparency that permits the contained solution to be visible from the outside. This property would have been reasonably expected to be preserved even when modified as suggested above by Hitoshi’s light-blocking film applied to the outer surface of the container, as Hitoshi et al. specifically teaches such light-blocking film to be wrapped around the barrel of the container, thereby permitting visualization of the contents on the top and/or bottom surface of the container to which the film has not been wrapped.
In claim 10, Applicant recites “[a] method for improving photostability’ of ripasudil when the aqueous ripasudil composition is stored in the recited package.
In claim 11, Applicant recites “[a] method for preserving” ripasudil when the aqueous ripasudil composition is stored in the recited package.
The above teachings clearly establish the prima facie obviousness of storing the aqueous ripasudil eye drop formulation of Hidaka et al. in the polyethylene or polypropylene container of Kimura et al. to which has been applied Hitoshi’s light-blocking film that blocks UV light with wavelength from 200 to nearly 400 nm (thereby circumscribing Applicant’s instantly claimed range of 300-335 nm) for the purpose of improving photostability of the aqueous ripasudil eye drop formulation when exposed to light, given the reasonable expectation of poor light stability of aqueous ripasudil in view of Hitoshi’s teachings.
The improvement in photostability also necessarily constitutes preservation of the aqueous ripasudil composition by minimizing decomposition and degradation of photosensitive aqueous ripasudil.
Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Claims 5-9 are rejected under 35 U.S.C. 103 as being unpatentable over Hidaka et al. (U.S. Patent Application Publication No. 2008/0064681 A1; 2008) in view of Hitoshi et al. (JP 09-024085 A; 1997, citing to the English translation submitted in the record by Applicant on 11/19/19) and Kimura et al. (U.S. Patent Application No. 2013/0281529 A1; Published October 24, 2013),
as applied above to claims 1, 3-5, 10 and 11,
further in view of Danielson et al. (U.S. Patent No. 6,602,447 B2; 2003) (of record, IDS cite no. 19) and Ammala et al. (‘Degradation Studies of Polyolefins Incorporating Transparent Nanoparticulate Zinc Oxide UV Stabilizers”, Journal of Nanoparticle Research, 2002; 4:167-174) (of record, IDS cito no. 61).
Hidaka in view of Hitoshi and Kimura differ from the instant claims only insofar as they do not explicitly teach that the polyethylene or polypropylene container contains an UV scattering agent or UV absorber (claim 5), particularly zinc oxide (claims 6-7), titanium oxide (claims 6,8), or a benzotriazole-based absorber (claims 6,9).
Danielson et al. teaches that UV absorber compounds are used in a number of protective applications, such as within transparent plastic containers, to combat the harmful and degradable effects of certain wavelengths of light in the UV spectrum (col.1, I.33-38). Danielson et al. teaches that commonly used UV absorbers include benzotriazoles (e.g., TINUVIN) and benzophenones (e.g., CYASORB), and that such compounds are highly effective in their UV absorber capacity (col.1, |.38-43).
Ammala et al. teaches that nanoparticulate metal oxides, such as titanium oxide (TiOz) and zinc oxide (ZnO), are known additives that protect against the damaging effects of UV radiation and do not affect product transparency (col.1, para.1, p.167). Ammala et al. teaches that nanoparticulate ZnO improves UV stability of polypropylene and high-density polyethylene (abstract).
A person of ordinary skill in the art before the effective filing date of the claimed invention would have had a reasonable expectation of success in further incorporating a UV absorbing agent into the polyethylene or polypropylene container of Kimura et al. because Danielson et al. teaches the use of UV absorber compounds in transparent plastic containers to minimize the harmful and degradable effects of UV light. The skilled artisan would have been motivated to incorporate such a UV absorbing agent into Kimura’s polyethylene or polypropylene container for the purpose of further reducing transmittance of UV light within the range of 200 to about 400 nm — the wavelength range disclosed by Hitoshi et al. to be relevant to the effective stabilization of poorly light stable and structurally similar fasudil. The skilled artisan would have recognized that such UV absorbing agent would have been suitably selected from those UV light absorbing agents known in the art before the effective filing date of the claimed invention - such as benzotriazoles, as taught by Danielson, or metal oxides, e.g., titanium oxide (TiOz) and/or zinc oxide (ZnO), as taught by Ammala — for this purpose with a reasonable expectation of successfully mitigating the detrimental effects of UV light on a transparent plastic container (such as Kimura’s transparent polyethylene or polypropylene container) containing an aqueous solution of a poorly light stable compound — in this case, ripasudil. It would, therefore, have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the polyethylene or polypropylene container of Kimura et al. to further incorporate a UV absorbing agent, such as a benzotriazole or metal (titanium or zinc) oxide, to further minimize the detrimental effects of UV light transmission of 200 to about 400 nm on the aqueous ripasudil formulation contained therein.
Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Conclusion
No claim is found to be allowable.
THIS ACTION IS MADE FINAL. 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 extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/HEATHER DAHLIN/Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/Supervisory Patent Examiner, Art Unit 1629