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.
Applicants' arguments, filed 06/29/2026, 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 Rejections and/or objections not reiterated from previous office actions are hereby withdrawn.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.
Regarding claim 1 reciting wherein the oleogel comprises at least one oily agent, the oleogel would comprise at least one oily agent when incorporated into the oil phase, which comprises peanut oil (i.e., oily agent).
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 when Igarashi teaches treating endometriosis with danazol in an oily solvent, it only does so when the composition is for non-vaginal administration.
The Examiner does not find Applicant’s argument to be persuasive. Igarashi discloses use of danazol for vaginal administration in a form of a liquid (abstract). Igarashi further discloses in the section on preparation for vaginal administration wherein for the solvent of the solution (i.e., liquid), see the paragraph of the preparation of non-vaginal administration (col. 1, lines 5-7). The paragraph on the preparation of non-vaginal administration discloses wherein examples of solvents include a lipiodol oily solution (col. 4, lines 47-48). Thus, Igarashi does teach wherein an oily solvent may be used for vaginal administration and wherein danazol may be in the oily solvent. As such, Igarashi does teach treating endometriosis with danazol in an oily solvent for vaginal administration and Applicant’s argument is unpersuasive.
Applicant argues that the office’s sole motivation for placing danazol in an organic phase (oily phase) is a post-filing-date reference.
The Examiner does not find Applicant’s argument to be persuasive. As discussed in the rejection, Mura et al. disclose wherein the internal hydrophobic phase contains hydrophobic excipients. Therefore, one of ordinary skill in the art would incorporate danazol into the phase that matches its hydrophobicity. Cayman Chemical was used as evidence to show that danazol is inherently hydrophobic since it is soluble in organic solvents, which are hydrophobic since peanut oil is an organic solvent. Thus, the motivation for placing danazol in an organic phase (oily phase) is from Mura et al. with Cayman Chemical providing evidence of an inherent property. As such, Applicant’s argument is unpersuasive.
Conclusion
Claims 1, 3, 5, 97, 102 and 105-109 are rejected.
No claims are allowed.
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 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 TRACY LIU whose telephone number is (571)270-5115. The examiner can normally be reached Mon-Fri 9 am - 5 pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Ali Soroush can be reached at 571-272-9925. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/TRACY LIU/Primary Examiner, Art Unit 1614
Prosecution Insights