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 Status
Claims 10, 12-15, and 18 are currently active and subject to examination.
Claim Rejections – Withdrawn – Overcome by Amendment
The rejection of claims 21-22 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention is withdrawn.
The rejection of claim(s) 10, 12, 13, 14, 15, 18 and 21-22 under 35 U.S.C. 103 as being unpatentable over Bell et al. (US7855190B2; Published 12/21/2010) is withdrawn.
The above rejections were overcome by Applicant’s amendments to the claims.
Claim Rejections – 35 USC § 103 – New Grounds of Rejection Necessitated by Amendment
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 10, 12-15, and 18 is/are rejected under 35 U.S.C. 103 as being unpatentable over Bell et al. (US7855190B2; Published Dec. 21, 2010) in view of Rubin et al. (US 2014/0256690 A1; Published Sept. 11, 2014).
Claim 10 recites:
PNG
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Bell teaches a method of providing contraception to a higher body weight female (>70 kg/ 154 lbs; >80 kg/ 176 lbs; >90 kg/ 198 lbs) the method comprising transdermally administering EE and LNG in amounts that encompass the claimed ranges (20-30 mcg EE; 154-516 mcg LNG), for a duration of at least about 20 days (bridged regimen) or at least about 50 days (bridged extended cycle regimen):
The invention is directed to a method of increasing the contraceptive effectiveness in a human female weighing about 70 kg or more, weighing about 80 kg or more, or weighing about 90 kg or more, by administering to the female the bridged regimen or the bridged extended cycle regimen.
Bell, Specification, column 20, lines 38-46 (emphasis added);
In accordance with the present invention, a female is administered an estrogen/progestin contraceptive regimen of a combined dosage form of estrogen and progestin (or progestogen) for a period of more than 20 consecutive days, followed by administration of estrogen for a period of about 2 to about 10 days, in which the daily dosage amounts of estrogen and progestin are equivalent to about 5 μg to about 50 μg of ethinyl estradiol and equivalent to about 0.02 mg to about 1.5 mg of levonorgestrel, respectively (“bridged regimen”).
In some aspects of the invention, the daily dosage amount of estrogen is equivalent to about 5 μg to about 25 μg of ethinyl estradiol. In other aspects of the invention, the daily dose of estrogen is equivalent to about 25 μg to about 40 μg of ethinyl estradiol. In yet other aspects of the invention, the daily dose of estrogen is equivalent to about 10 μg to about 30 μg of ethinyl estradiol. In some aspects of the invention, the daily dose of estrogen is equivalent to about 20 μg of ethinyl estradiol. In other aspects, it is equivalent to about 30 μg of ethinyl estradiol.
In some aspects of the invention, the daily dosage amount of progestin is equivalent to about 0.01 mg to about 0.25 mg of levonorgestrel. In other aspects of the invention, the daily dose of progestin is equivalent to about 0.05 mg to about 0.20 mg of levonorgestrel.
Bell, Specification, columns 6-7 (emphasis added);
The estrogen and progestin are administered in the conventional manner by any route where they are active. For example, administration can be by, but is not limited to, parenteral, subcutaneous, intravenous, intramuscular, intraperitoneal, transdermal, buccal, or ocular routes, or intravaginally, by inhalation, by depot injections, or by hormone implants. Thus, modes of administration for the estrogen and progestin (either alone or in combination with other pharmaceuticals) can be, but are not limited to, sublingual, injectable (including short-acting, depot, implant and pellet forms injected subcutaneously or intramuscularly), vaginal creams, suppositories, pessaries, rings, rectal suppositories, intrauterine devices, and transdermal forms such as patches and creams.
Bell, Specification, column 26, lines 48-61 (emphasis added);
The invention is directed to a method of increasing contraceptive effectiveness in a higher weight female in need thereof, the method comprising administering to the female a combination of estrogen and progestin for a period of more than 50 consecutive days, followed by administration of estrogen for a period of about 2 to about 10 consecutive days; wherein the higher weight female weighs about 70 kg or more.
Bell, column 4, lines 40-47.
Therefore, it is commonly known in the art that contraception can be effected in women having body weights greater than 154 pounds, greater than 176 pounds, and greater than 198 pounds by administering transdermally EE in amounts of 20 to 30 micrograms and LNG in amounts between 20 and 1500 micrograms, 10 to 250 micrograms, and 50 to 200 micrograms. The preferred amounts of EE (20 and 30 micrograms) are within the claimed range. The disclosed ranges of LNG encompass the claimed ranges and the preferred ranges overlap the claimed ranges. As stated in the MPEP, a prima facie case of obviousness exists when the claimed ranges overlap or lie inside those in the prior art:
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) (The prior art taught carbon monoxide concentrations of "about 1-5%" while the claim was limited to "more than 5%." The court held that "about 1-5%" allowed for concentrations slightly above 5% thus the ranges overlapped.); In re Geisler, 116 F.3d 1465, 1469-71, 43 USPQ2d 1362, 1365-66 (Fed. Cir. 1997) (Claim reciting thickness of a protective layer as falling within a range of "50 to 100 Angstroms" considered prima facie obvious in view of prior art reference teaching that "for suitable protection, the thickness of the protective layer should be not less than about 10 nm [i.e., 100 Angstroms]." The court stated that "by stating that ‘suitable protection’ is provided if the protective layer is ‘about’ 100 Angstroms thick, [the prior art reference] directly teaches the use of a thickness within [applicant’s] claimed range."). See also In re Bergen, 120 F.2d 329, 332, 49 USPQ 749, 751-52 (CCPA 1941) (The court found that the overlapping endpoint of the prior art and claimed range was sufficient to support an obviousness rejection, particularly when there was no showing of criticality of the claimed range)
MPEP § 2144.05 Obviousness of Similar and Overlapping Ranges, Amounts, and Proportions [R-01.2024].
While Bell teaches that the method is a bridged regimen, with an additional treatment step comprising administering estrogen only, one of ordinary skill in the art would have a reasonable expectation of success to effect contraception in a higher body weight woman with treatment step consisting of only transdermally administering LNG and EE in the claimed amounts because it is commonly known in the art that contraception can be effected in higher body weight women using only this single treatment step.
For example, Rubin teaches a method of effecting contraception in a higher body weight woman, comprising trasdermally administering LNG and EE for at least three weeks in amounts effective to effect contraception:
[0045] In an illustrative embodiment of the invention, if a woman seeking contraception is excessively overweight, i.e., has a BMI=>30 and/or has a body weight of =>90 Kg, she can utilize a transdermal hormone delivery device, e.g., a patch, that delivers levonorgestrel and she can be confident, based on statistical analyses of populations of women who have used such patch, that the probability that the patch will be effective in preventing her from becoming pregnant will be approximately, if not exactly, or if not even greater than, what it would be were she in a different weight category.
[0046] In illustrative embodiments, the patch comprises a progestin, e.g., levonorgestrel, and an estrogen, such as estradiol or ethinyl estradiol. A treatment cycle typically comprises 4 weeks, having a 3 week treatment interval and a 1 week rest interval. During the treatment interval, a new patch is applied at the start of each week. During the rest interval, no patch is worn or a patch can be worn that is a placebo or that provides only low doses of a progestin or an estrogen or both.
[0047] In such illustrative embodiments, the mean steady state plasma concentration of ethinyl estradiol in a population of subjects (overweight and non-overweight) is about (e.g., +/−10%) 30 to about 50 pg/mL, e.g., 35 to 45 pg/mL, by the second week of a second treatment cycle, i.e., by the second week of a second treatment cycle, and during each week on patch during subsequent cycles, in patients with detectable levels of hormone (ethinyl estradiol or levonorgestrel) during patch wear. In certain such embodiments, the mean steady state plasma concentration of ethinyl estradiol in a population of subjects does not exceed about 70 pg/mL during any week of any treatment cycle. In certain such embodiments, the mean steady state plasma concentration of ethinyl estradiol in a population of subjects does not exceed about 60 pg/mL during any week of any treatment cycle. In certain such embodiments, the mean steady state plasma concentration of ethinyl estradiol does not exceed about 50 pg/mL during any week of any treatment cycle.
[0048] In illustrative embodiments, the mean steady state plasma concentration of levonorgestrel in a population of subjects (overweight and non-overweight) is about (e.g., +/−10%) 800 to about 2500 pg/mL, e.g., 900 to 2400 pg/mL, by the second week of a second treatment cycle, i.e., by the second week of a second treatment cycle, and during each week on patch during subsequent cycles, in patients with detectable levels of hormone (ethinyl estradiol or levonorgestrel) during patch wear.
[0049] In illustrative embodiments, the ratio of the mean steady state plasma concentration of levonorgestrel to the mean steady state plasma concentrations of ethinyl estradiol in a population of subjects (overweight and non-overweight) is about 30 to about 60.
Rubin, Specification, paragraphs [0045-0049].
The claimed invention amounts to nothing more than a routine optimization of a result-effective variable commonly known in the art. It is known that estrogen and progesterone can be transdermally administered in amounts that encompass the claimed ranges (20-30 mcg EE; 154-516 mcg LNG) for contraception in higher body weight women. It is known in the art that the treatment step can consist of only administering EE and LNG in these amounts. It is also known in the art that the dose can be increased to maintain mean steady state plasma levels of LNG and EE in higher body weight women. The Applicant has demonstrated nothing inventive by applying known mathematical dose-response equations to estimate effective doses of LNG and EE in higher-body weight women.
Therefore, claim 10 was prima facie obvious at the time of filing.
Claim 12 recites:
The method of claim 10, wherein when the woman has a body weight of 200 pounds or more, the dose is:(i) 340 micrograms per day of levonorgestrel and 30 micrograms per day of ethinyl estradiol; (ii) 260 micrograms per day of levonorgestrel and 30 micrograms per day of ethinyl estradiol; or(iii) 200 micrograms per day of levonorgestrel and 30 micrograms per day of ethinyl estradiol.
As shown above, Bell teaches a method of effecting contraception in a woman with a body weight greater than 90 kg/ 198 pounds comprising administering 5 μg to about 50 μg of ethinyl estradiol, specifically 20 or 30 μg if EE, and about 20 μg to about 1500 μg of levonorgestrel, specifically, 10 to 250 μg, and 50 to 200 μg. These ranges encompass, overlap, or are close to the claimed amounts. Therefore, one of ordinary skill in the art would have a reasonable expectation of success to effect contraception in a woman having a body weight greater than 200 pounds comprising administering 30 μg of EE with 200, 260 or 340 μg of LNG. Therefore, claim 12 was prima facie obvious at the time of filing.
Claim 13 is directed towards: “The method of claim 12, wherein dose (i) is initially administered to the woman and if side effects develop then dose (ii) is administered instead and if side effects develop then dose (iii) is administered instead.” It is commonly known in the art that administration of synthetic estrogens and progestins can produce side effects/ adverse events. For example, Bell teaches that adverse events occurred when LNG and EE were administered to patients:
Adverse events reported by patients during the course of the clinical studies of Example 7 were recorded. An “adverse event” was defined as any reaction, side effect, or other undesirable event that occurred in conjunction with the use of the drug, biological product or diagnostic agent during the study, whether or not the event was considered to be related to the study drug (see the protocol in Example 5). The percentage of patients in the first and second clinical studies reporting certain adverse events are presented in Tables 14 through 20. Each table also includes similar data from the third clinical study.
Bell, Specification, column 49, lines 29-40.
As shown above Bell also teaches ranges of LNG and EE that encompass the claimed amounts. Bell specifically teaches that the treatment should produce a clinically significant response without excessive levels of side effects (Bell, Specification, column 10, lines 10-11) Accordingly, one of ordinary skill in the art would have a reasonable expectation of success to optimize the amount of LNG for the appearance of side effects and deliver 340, 260 or 200 mcg of LNG to the patient.
Therefore, claim 13 was prima facie obvious at the time of filing.
Claim 14 is directed towards:
“The method of claim 10, wherein the woman has a body weight of 200 pounds or more, comprising administering to the woman:
420 micrograms per day of levonorgestrel and 20 micrograms per day of ethinyl estradiol;
330 micrograms per day of levonorgestrel and 20 micrograms per day of ethinyl estradiol; or
220 micrograms per day of levonorgestrel and 20 micrograms per day of ethinyl estradiol.”
Claim 14.
As shown above, Bell teaches a method of effecting contraception in a woman with a body weight greater than 90 kg/ 198 pounds comprising administering 5 μg to about 50 μg of ethinyl estradiol, specifically 20 or 30 μg if EE, and about 20 μg to about 1500 μg of levonorgestrel, specifically, 10 to 250 μg, and 50 to 200 μg. These ranges encompass, overlap, or are close to the claimed amounts. Therefore, one of ordinary skill in the art would have a reasonable expectation of success to effect contraception in a woman having a body weight greater than 200 pounds comprising administering 30 μg of EE with 220, 330 or 420 μg of LNG. Therefore, claim 14 was prima facie obvious at the time of filing.
Claim 15 is directed towards: “The method of claim 14, wherein dose (i) is initially administered to the woman and if side effects develop then dose (ii) is administered instead and if side effects develop then dose (iii) is administered instead.”
The rejection of claim 13 is incorporated herein by reference and as such claim 15 was prima facie obvious at the time of filing.
Claim 18 is directed towards: “The method of claim 10, wherein the dose of the ethinyl estradiol is varied during a treatment cycle or the dose of the levonorgestrel is varied during a treatment cycle, or both”.
One of ordinary skill in the art would have a reasonable expectation of success to vary the amounts of LNG and/or EE in the treatment cycle because these regimens are commonly known in the art. For example, Bell teaches that the estrogen and progestin can be administered monophasically, biphasically, triphasically, or multiphasically:
In the disclosed bridged regimen, the combined dosage form of estrogen and progestin can be administered monophasically, biphasically, triphasically, or multiphasically. As used herein, “monophasic” refers to the continuous use of one particular dose of estrogen and progestin during the period of administration of the combined dosage form of estrogen and progestin. “Biphasic” refers to administration of a first continuous dose of estrogen and progestin during a first portion of the period of administration of the combined dosage form of estrogen and progestin, with administration of a second continuous dose of estrogen and progestin during the second portion of the period of administration of the combined dosage form. “Triphasic” refers to administration of first, second, and third continuous doses of estrogen and progestin during the first, second, and third portions, respectively, of the period of administration of the combined dosage form of estrogen and progestin. “Multiphasic” refers to administration of four or more continuous doses of estrogen and progestin during the first, second, third, and fourth or more portions, respectively, of the period of administration of the combined dosage form of estrogen and progestin.
Bell, Specification, col. 7-8.
Therefore, claim 21 was prima facie obvious at the time of filing.
Given the above teachings, the invention as a whole was prima facie obvious at the time of filing.
Conclusion
No claim is found to be allowable.
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/HEATHER DAHLIN/Examiner, Art Unit 1629