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 .
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
1. Claim 123 is rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Mantelle (US 2016/0015655 A1, Jan. 21, 2016) (hereinafter Mantelle).
Mantelle discloses a method for administering estradiol, comprising applying to the skin or mucosa of a subject in need thereof a transdermal drug delivery system comprising a drug-containing layer defining an active surface area and comprising a polymer matrix comprising estradiol, and is effective to deliver an amount of estradiol per day of about 0.025 mg/day (i.e., 25 mcg/day) ([0010]). The polymer matrix of Example 1 comprises acrylic adhesive, silicone adhesive, povidone, oleyl alcohol, dipropylene glycol, and estradiol (i.e., wherein the estrogen is the only active pharmaceutical ingredient in the transdermal system). The polymer matrix is applied to a release liner (i.e., backing) ([0089]).
Accordingly, Mantelle anticipates the instant claims insofar as disclosing a method for administering estradiol (i.e., an estrogen), comprising applying to the skin or mucosa of a subject in need thereof a transdermal drug delivery system comprising a drug-containing layer comprising a polymer matrix comprising estradiol, delivering an amount of estradiol per day of about 0.025 mg/day (i.e., 25 mcg/day) ([0010]) applied to a release liner (i.e., backing), wherein the estradiol (i.e., estrogen) is the only active pharmaceutical ingredient in the transdermal system ([0089]).
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
2. Claims 108-122 and 124-127 are rejected under 35 U.S.C. 103 as being unpatentable over Rubin et al., (US 2014/0256690 A1, Sept. 11, 2014) (cited by applicant on IDS 08/08/2025) (hereinafter Rubin).
Rubin discloses a method of using a transdermal hormone delivery system (“THDS”) comprising a progestin that comprises applying the THDS, i.e., the patch, to the skin of a woman who is overweight, e.g., excessively overweight ([0013]) and relates to a method of effecting contraception, i.e., reducing the risk of pregnancy (i.e., a condition responsive to an estrogen) ([0014]). The invention comprises a method for manufacturing a transdermal patch, said patch comprising a progestin and an estrogen ([0020]). The patch comprises levonorgestrel and ethinyl estradiol and delivers these hormones in such doses as to result in exposure to levonorgestrel to be at least about 20-fold greater than exposure to ethinyl estradiol ([0022]) but the progestin may be other than levonorgestrel and the ratio of exposure to the progestin to exposure to the estrogen is equivalent to a levonorgestrel:ethinyl estradiol ratio of at least 20, e.g., 30 to 50, based on the potency of the other progestin relative to the potency of levonorgestrel. The THDS comprises a backing layer and an adhesive polymer matrix affixed to the backing layer, wherein the adhesive matrix comprises: a) a pressure sensitive adhesive polymer; b) a humectant; c) a skin permeation enhancer; d) a progestin; e) an estrogen (Claim 24). The probability that the patch will be effective in the case of an excessively overweight or large woman is approximately equal to the probability that the patch would be effective in the case of a woman who is not excessively overweight or large ([0033]). “Excessively overweight” means “obese,” which will be used to describe a woman whose Body Mass Index (BMI) is equal to or greater than 30 Kg/m2([0042]). Skin permeation enhancers include oleyl alcohol ([0072]). Suitable progestins include norelgestromin present in a concentration based on weight of the transdermal composition (i.e., wt %) of 0.1 to 3% that varies based on various factors especially the skin permeation rate and the relative potency of the progestin ([0086]). Estrogens include ethinyl estradiol present in a concentration based on weight of the transdermal composition (i.e., wt %) of 0.1 to 3% ([0088]). A transdermal dosage unit designed for one-week therapy should deliver at least about 20 μg/day of levonorgestrel, e.g., about 50 to about 100 μg/day (or an equivalent effective amount of another progestin) and 10-50 μg/day of ethinyl estradiol. Those respective amounts of progestin and estrogen are believed to be necessary to inhibit ovulation and to maintain normal female physiology and characteristics ([0089]). Fig. 2 shows that during Cycle 1, Week 1, ethinyl estradiol concentrations peak around 48 hours and begin noticeably decreasing around 168 hours (i.e., constant estrogen release at about 48 hours to about 168 hours) (Fig. 2). The progestin compound and the estrogenic steroid are ordinarily dispersed or dissolved concurrently in fabricating the hormone-containing adhesive polymer matrix ([0092]). The adhesive polymer composition comprising the AI (active ingredient) and the volatile component(s) is applied to the backing layer material (i.e., mixing estrogen with an adhesive and applying it to the transdermal system) ([0147]). The AUC0-168(pg-hr/mL) (i.e., AUCtau), t1/2 mean AUC0-168(i.e., AUC∞) and Cmax for ethinyl estradiol over a period of one week (i.e., seven days) are disclosed in Tables 5 and 6. For levonorgestrel the AUC0-168(ng-hr/mL) (i.e., AUCtau) and t1/2 were between 120.0 – 378.0 and 38.2 to 40.5, respectively (Table 5). The EE exposure (AUC) from the Patch of Rubin is approximately 50% less than for Ortho Evra ([0174]).
Rubin discloses a transdermal hormone delivery system (“THDS”) ([0013]) effecting contraception ([0014]) containing a backing layer and an adhesive polymer matrix affixed to the backing layer ([0024]) delivering 10-50 μg/day of ethinyl estradiol (i.e., an estrogen) ([0089]). Together these would provide a composition as claimed instantly. The prior art is not anticipatory insofar as these combinations must be selected from various lists/locations in the reference. It would have been obvious, however, to make the combination since all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results to one of ordinary skill in the art. See MPEP 2143(I)(A).
Regarding the limitations of claims 111 and 122 reciting ethinyl estradiol is in the matrix in an amount of about 0.21 mg to about 0.48 mg per patch or film and about 0.21 mg to about 0.48 mg of estrogen, as discussed above, Rubin teaches ethinyl estradiol present in a concentration based on weight of the transdermal composition (i.e., wt %) of 0.1 to 3% and that a transdermal dosage unit designed for one-week therapy should deliver at least 10-50 μg/day of ethinyl estradiol. Accordingly, one of ordinary skill in the art would have arrived at an amount of ethinyl estradiol of about 0.21 mg to about 0.48 mg per patch through routine experimentation based on the desired daily dose of ethinyl estradiol as taught by Rubin. 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).
Regarding the claimed AUC∞, AUCtau, t1/2, and Cmax of ethinyl estradiol and norelgestromin in claims 113, 114, 119, and 120, as discussed above, Rubin discloses wherein the amount of progestin and estrogen are necessary to inhibit ovulation and to maintain normal female physiology and characteristics. Therefore, it would have been obvious to have optimized to the claimed amount of estrogen (i.e., ethinyl estradiol) and progestin (i.e., norelgestromin) depending on the level of ovulation inhibition and maintenance of female physiology and characteristics desired. After arriving at such amount, the claimed AUC∞, AUCtau, t1/2, and Cmax would have been obvious since these properties are dependent on the amount of estrogen (i.e., ethinyl estradiol) and progestin (i.e., norelgestromin) administered. 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).
Regarding the limitation of claim 118 reciting norelgestromin is released from the transdermal system in an amount from about 190 to about 210 mcg per day, as discussed above, Rubin discloses wherein the amount of progestin is necessary to inhibit ovulation and to maintain normal female physiology and characteristics. Therefore, it would have been obvious to have optimized to the release rate of norelgestromin (i.e., a progestin) depending on the level of ovulation inhibition and maintenance of female physiology and characteristics desired. 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).
Regarding the limitations of claim 124 reciting the human female patient has a body mass index (BMI) of less than 30 kg/m2, as discussed above, Rubin teaches that the probability that the patch will be effective in the case of an excessively overweight or large woman is approximately equal to the probability that the patch would be effective in the case of a woman who is not excessively overweight or large and “excessively overweight” means “obese,” which will be used to describe a woman whose Body Mass Index (BMI) is equal to or greater than 30 Kg/m2([0042]). Accordingly, it would have been obvious to one of ordinary skill in the art to administer the patch of Rubin to a human female patient having a body mass index (BMI) of less than 30 kg/m2 since the probability that the patch will be effective in the case of an excessively overweight or large woman is approximately equal to the probability that the patch would be effective in the case of a woman who is not excessively overweight (i.e., a body mass index (BMI) of less than 30 kg/m2) as taught by Rubin.
Regarding the limitation of claim 126 reciting wherein the patient has a lower risk of venous thromboembolism events as compared to a patient receiving more than 28 mcg per day of estrogen, as discussed above, the THDS of Rubin delivers 10 μg/day of ethinyl estradiol (i.e., estrogen), thus, it would be obvious that patients would have a lower risk of venous thromboembolism events as compared to a patient receiving more than 28 mcg per day of estrogen since 10 μg/day is less than 28 mcg per day.
Conclusion
Claims 108-127 are rejected.
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Samantha J Knight whose telephone number is (571)270-3760. The examiner can normally be reached Monday - Friday 8:30 am to 5:00 pm ET.
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.
/S.J.K./Examiner, Art Unit 1614
/TRACY LIU/Primary Examiner, Art Unit 1614