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 . Claims included in the prosecution are claims 1, 3, 5, 97, 102 and 105-109.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 12/16/2025 has been entered.
Applicants' arguments, filed 12/16/2025, have been fully considered. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
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.
Claims 1, 3, 5, 97, 102 and 105-109 are rejected under 35 U.S.C. 103 as being unpatentable over Igarashi (EP 0501056 A1, Sep. 2, 1992) in view of Okada et al. (US 4,211,769, Jul. 8, 1980), Mura et al. (US 2011/0195944, Aug. 11, 2011), Silberstein (US 2013/0295204, Nov. 7, 2013), and Ron (US 2015/0004213, Jan. 1, 2015), as evidenced by Cayman Chemical (Product Information: Danazol, Nov. 16, 2022) and O’Sullivan et al. (Edible oleogels for the oral delivery of lipid soluble molecules: Composition and structural design considerations, 2016).
Igarashi discloses a therapeutic agent of endometriosis for vaginal administration, which comprises 0.5-100 mg of danazol as a unit dose in a form of a solution (claim 1). The preparation for vaginal administration is administered in its unit dose everyday or every 2-4 days (col. 5, lines 11-13).
Igarashi differs from the instant claims insofar as not disclosing wherein the solution is a two-phase liquid emulsion comprising an aqueous gel comprising a bioadhesive and an organic phase comprising at least one oily agent.
However, Okada et al. disclose preparations for vaginal administration (col. 1, lines 5-6). The preparation may be in any form that can be administered into the vagina. Thus, it may be used in any of such dosage forms such as aqueous solutions (col. 2, lines 3-6). The aqueous solution may be administered after it has been made into an oil-in-water or water-oil-water emulsion (col. 6, lines 14-16).
Mura et al disclose an oil-in-water emulsion topically applied into the vaginal cavity by a suitable applicator (¶ [0014]). The internal hydrophobic phase contains hydrophobic excipients, such as peanut oil (i.e., claimed oily agent) (¶ [0015]). The emulsion contains an external hydrophilic phase in amounts ranging between 60 to 99% by weight. The hydrophilic phase contains not more than 80% by weight of purified water (¶ [0016]). The emulsion may contain jellifying agents (¶ [0020]). Example 1 discloses a jellified oil-in-water emulsion comprising 1.00% polycarbophil (¶ [0024]). Polycarbophil was added after Phase A (oil phase) was added to Phase B (aqueous phase) and was mixed. Afterwards, the formulation was gently mixed until a homogenous jellified emulsion was obtained (¶ [0025]).
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art to have incorporated the danazol of Igarashi into the oil-in-water emulsion (i.e., two-phase liquid emulsion) of Mura et al. since Igarashi discloses wherein danazol is suitable in a solution for vaginal administration, solutions for vaginal administration may be administered as emulsions as taught by Okada et al., and the emulsion of Mura et al. is a known and effective emulsion for vaginal administration as taught by Mura et al.
Regarding claim 1 reciting wherein the aqueous gel comprises a bioadhesive, the aqueous phase of the emulsion of Mura et al. comprises polycarbophil (i.e., claimed bioadhesive) since the emulsion is an oil-in-water emulsion and polycarbophil was added after the phases have been mixed. The aqueous phase of the emulsion of Mura et al. is an aqueous gel since it comprises polycarbophil, which is a jellifying agent.
Regarding claim 1 reciting an organic phase, the oil phase of Mura et al. is an organic phase since it comprises peanut oil, which is an organic compound.
Regarding claim 1 reciting wherein the danazol is dissolved in the organic phase, as evidenced by Cayman Chemical, danazol is soluble in organic solvents. Therefore, since the oil phase of Mura et al. comprises peanut oil (i.e., organic solvent), it would have been obvious to one of ordinary skill in the art to have incorporated danazol in the oil phase (i.e., claimed organic phase) of Mura et al.
The combined teachings of Igarashi, Okada et al., and Mura et al. do not teach wherein the oil phase comprises oleogel.
However, Silberstein discloses a pharmaceutical composition that may be vaginally administered (¶ [0113]). The composition may comprise a gelling agent such as oleogels (¶ [0077]).
As discussed above, Mura et al. disclose wherein the emulsion comprises jellifying agents. Accordingly, it would have been prima facie obvious to one of ordinary skill in the art to have incorporated oleogel into the emulsion of Mura et al. since oleogel is a known and effective gelling agent for vaginal administration as taught by Silberstein.
Regarding the composition comprising both polycarbophil and oleogel as jellifying agents, it is prima facie obvious to combine two compositions, each of which is taught by the prior art to be useful for same purpose, in order to form a third composition to be used for the very same purpose. The idea for combining them flows logically from their having been individually taught in the prior art. See MPEP 2144.06. Thus, since polycarbophil and oleogel are both known jellifying agents, combining oleogel with polycarbophil as the jellifying agent would have been obvious.
Regarding claim 1 reciting oleogel being present in the organic phase, as evidenced by O’Sullivan et al., oleogelators are soluble in oil (page 60, first full paragraph). As discussed above, Mura et al. disclose wherein the oil phase comprises hydrophobic excipients. As such, it would have been obvious to one of ordinary skill in the art to have incorporated oleogel into the oil phase (i.e., claimed organic phase) since it is hydrophobic.
The combined teachings of Igarashi, Okada et al., Mura et al., and Silberstein do not disclose wherein administering the composition produces a zero-order release rate profile of danazol into a peritoneal tissue of the human female subject at least about 8 hours after the administration of the composition.
However, Ron discloses drug delivery devices (e.g., polymeric vaginal rings) with a favorable release profile (abstract). In order to achieve constant levels of each of one or more active agents and avoid the inefficiencies of concentration peaks and valleys, active agents can be released from a delivery device at a rate that does not substantially change with time (so called zero-order release) (¶ [0060]). The drug delivery device can provide for substantially “zero order kinetic” active agent administration (¶ [0061]). Systemic administration using a vaginal device can result in a peak serum concentration of the active agent in a patient at about 12 to about 22 hours after insertion of the device (¶ [0059]). Generally, the agent can be present in an amount which will be released over controlled periods of time, according to predetermined desired rates, which rates are dependent, at least in part, upon the initial concentration of the active substance in the polymer (¶ [0066]). The polymer can be capable of being degraded by ultrasonic energy such that any incorporated agent is released at a rate within a desired release range, or, in the case of nondegradable polymers, release is enhanced (¶ [0073]). Different polymers have different release rates (¶ [0050]).
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art to have formulated the composition of the prior art to have a zero-order release rate profile of the active agent in order to achieve constant levels of active agent and avoid the inefficiencies of concentration peaks and valleys as taught by Ron. One of ordinary skill in the art would have had a reasonable expectation of success since amount of active agent and type of polymer affects release rate as taught by Ron.
In regards to instant claim 1 reciting a peritoneal tissue, since the composition of the prior art is substantially in the same form as the claimed invention and is administered vaginally like the claimed invention, the composition of the prior art would release active agent into a peritoneal tissue like the claimed invention.
It would have been prima facie obvious to one of ordinary skill in the art to have formulated the composition such that the active agent is present in the peritoneal tissue at about 12 to about 22 hours after administering of the pharmaceutical composition since this is a favorable release profile as taught by Ron.
In regards to instant claim 102 reciting wherein following the vaginal administration of the two-phase liquid emulsion, an amount of endometrial deposits in the peritoneal cavity of the human female subject is reduced as compared to the amount of endometrial deposits before the vaginal administration of the two-phase liquid emulsion, since the two-phase liquid emulsion of the prior art comprises danazol and danazol treats endometriosis, following the vaginal administration of the two-phase liquid emulsion of the prior art, an amount of endometrial deposits in the peritoneal cavity of the human female subject would be reduced as compared to the amount of endometrial deposits before the vaginal administration of the two-phase liquid emulsion.
In regards to instant claim 106 reciting wherein the two-phase liquid emulsion minimizes vaginal clumping or discharge in the human female subject relative to a two-phase liquid emulsion that does not comprise a bioadhesive, since the two-phase liquid emulsion of the prior art comprises polycarbophil (i.e. claimed bioadhesive), the two-phase liquid emulsion of the prior art would minimize vaginal clumping or discharge in a human female subject relative to a two-phase liquid emulsion that does not comprise a bioadhesive.
In regards to instant claim 109 reciting wherein the two-phase liquid emulsion is vaginally administered to the human female subject daily for 30 consecutive days, since Igarashi discloses wherein danazol treats endometriosis, it would have taken no more than the relative skills of one of ordinary skill in the art through routine experimentation to have arrived at the claimed duration depending on the duration needed to sufficiently treat endometriosis. Where 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. See MPEP 2144.05(II)(A).
Response to Arguments
Applicant argues that emulsions of Okada comprise peptides, whereas the embodiments claimed comprise danazol – a steroid, not a peptide. In view of this, the skilled artisan would not be motivated to incorporate danazol – a steroid – into the organic phase of a two-phase emulsion as claimed. Instead, according to Igarashi, danazol is placed in an oily phase when used for non-vaginal administration.
The Examiner does not find Applicant’s argument to be persuasive. The rejection does not state incorporating danazol into the emulsion of Okada. The rejection states to incorporate danazol into the emulsion of Mura since Igarashi discloses wherein danazol is suitable in a solution for vaginal administration, solutions for vaginal administration may be administered as emulsions as taught by Okada, and the emulsion of Mura is a known and effective emulsion for vaginal administration. Applicant has not argued why one of ordinary skill in the art would not incorporate danazol into the emulsion of Mura. Therefore, Applicant’s argument is unpersuasive. Also, one of ordinary skill in the art would have incorporated danazol into the oil phase (i.e., organic phase) of Mura’s vaginally applied emulsion since as evidenced by Cayman Chemical, danazol is soluble in organic solvents and the oil phase of Mura comprises peanut oil (i.e., organic solvent).
Conclusion
Claims 1, 3, 5, 97, 102 and 105-109 are rejected.
No claims are allowed.
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/TRACY LIU/Primary Examiner, Art Unit 1614