Warner Chilcott Company v. Lupin Atlantis Holdings Et. Al.

IN THE UNITED STATES DISTRICT COURT
FOR THE DISTRICT OF MARYLAND

WARNER CHILCOTT COMPANY, LLC,
Union St., Road 195, Km. 1.1
Fajardo, Puerto Rico

Plaintiff,

v.

LUPIN ATLANTIS HOLDINGS SA
Mhlentalstrasse 2
8200 Schaffhausen
Schaffhausen, Switzerland

LUPIN LTD.
B/4 Laxmi Towers,
Bandra Kurla Complex, Bandra (E),
Mumbai 400 051 India

LUPIN PHARMACEUTICALS, INC.
111 S. Calvert Street,
21st Floor,
Baltimore, MD 21202
Baltimore City

Defendants.

C.A. No. _________________

COMPLAINT FOR PATENT INFRINGEMENT
Plaintiff Warner Chilcott Company, LLC, by its undersigned attorneys, brings this
action against Defendants Lupin Atlantis Holdings SA; Lupin Ltd.; and Lupin
Pharmaceuticals, Inc. (collectively Lupin), and hereby alleges as follows:
THE PARTIES
1. Plaintiff Warner Chilcott Company, LLC (Warner Chilcott) is a limited
liability company organized and existing under the laws of Puerto Rico, having offices at
Union St., Road 195, Km 1.1, Fajardo, Puerto Rico.
2. Upon information and belief, Defendant Lupin Limited (Lupin Ltd.) is a
corporation organized and existing under the laws of India.
3. Upon information and belief, Defendant Lupin Atlantis Holdings SA (Lupin
Atlantis) is a wholly-owned subsidiary of Lupin Ltd., and is a corporation organized and
existing under the laws of Switzerland.
4. Upon information and belief, Defendant Lupin Pharmaceuticals, Inc. (Lupin
Pharmaceuticals) is a wholly-owned subsidiary of Lupin Ltd. and is a corporation
organized and existing under the laws of the Commonwealth of Virginia. Lupin
Pharmaceuticals has a principal place of business located at 111 S. Calvert Street, 21st
Floor, Baltimore, MD 21202.
5. Upon information and belief, Lupin Ltd. has engaged in continuous and
systemic contacts with the United States by, among other things, filing with the United
States Food and Drug Administration (FDA) Abbreviated New Drug Applications
(ANDAs) to sell various products in the United States. Upon information and belief,
2

Lupin Ltd. manufactures generic drug products for sale and use in the United States,
including in this judicial district.
6. Upon information and belief, Lupin Ltd., Lupin Atlantis, and Lupin
Pharmaceuticals are agents of each other with respect to the development, regulatory
approval, marketing, sale and/or distribution of generic pharmaceutical products. Upon
information and belief, Lupin Ltd. and Lupin Pharmaceuticals, through their affiliate,
agent, and alter-ego Lupin Atlantis, filed the ANDA with FDA that is at issue in this
patent infringement suit. Upon information and belief, the acts of Lupin Atlantis
complained of herein were done and are being done with the cooperation, participation,
and assistance of, and at least in part for the benefit of, Lupin Ltd. and Lupin
Pharmaceuticals.
JURISDICTION AND VENUE
7. This is an action for patent infringement arising under the patent laws of the
United States, 35 U.S.C. 271(e)(2) and 21 U.S.C. 355. This Court has subject matter
jurisdiction over this action based on 28 U.S.C. 1331 and 1338(a).
8. This Court has personal jurisdiction over Lupin Pharmaceuticals by virtue of,
at least, its principal place of business in Baltimore, MD.
9. This Court has personal jurisdiction over Lupin Atlantis at least under
Federal Rule of Civil Procedure 4(k)(2).
10. This Court has personal jurisdiction over Lupin Ltd. at least under Federal
Rule of Civil Procedure 4(k)(2).
3

11. Venue is proper in this Court under 28 U.S.C. 1391 and 1400(b).
COUNT I: CLAIM FOR INFRINGEMENT OF THE 050 PATENT
12. Warner Chilcott LLC is the holder of New Drug Application (NDA) No.
203667 for Minastrin
24 Fe, which contains the active ingredients ethinyl estradiol and

norethindrone acetate. Minastrin
24 Fe was approved by FDA on May 8, 2013, and is

indicated for use by women to prevent pregnancy. Minastrin
24 Fe is sold as a 28-day
oral contraceptive regimen that includes 24 chewable tablets comprising 1.0 mg
norethindrone acetate and 0.020 mg ethinyl estradiol, and 4 chewable ferrous fumarate
tablets (placebo).
13. U.S. Patent No. 6,667,050 (the 050 Patent) entitled Chewable Oral
Contraceptive was lawfully issued by the United States Patent and Trademark Office on
December 23, 2003. A copy of the 050 Patent is attached as Exhibit A.
14. Warner Chilcott is the sole owner of the 050 Patent.
15. The 050 Patent claims, among other things, chewable, palatable oral
contraceptive tablets; methods of administering said tablets to a human female; and
methods of enhancing compliance with the oral contraception regimen.
16. Minastrin
24 Fe and its use in accordance with the FDA-approved labeling

are covered by the claims of the 050 Patent. The 050 Patent is listed in FDAs Approved
Drug Products with Therapeutic Equivalence Evaluations (the Orange Book) for
Minastrin
24 Fe.
4

17. Upon information and belief, Lupin Ltd. and Lupin Pharmaceuticals, through
their affiliate, agent, and alter-ego Lupin Atlantis, submitted ANDA No. 206287 to FDA
seeking approval to engage in the commercial manufacture, use, offer for sale, and sale of
a generic version of Minastrin
24 Fe before the expiration of the 050 Patent. Defendants

manufacture, use, offer for sale, or sale in the United States, or importation into the
United States, of such product would infringe the claims of the 050 Patent under 35
U.S.C. 271(a), (b), and/or (c).
18. Defendants manufacture, use, offer for sale, or sale in the United States, or
importation into the United States, of the generic Minastrin
24 Fe product for which

approval is sought in ANDA No. 206287 would actively induce and contribute to
infringement of the 050 Patent, and Defendants would be liable under 35 U.S.C. 271(b)
and/or (c).
19. As part of their ANDA filing, Lupin Ltd. and Lupin Pharmaceuticals, through
their affiliate, agent, and alter-ego Lupin Atlantis, have purportedly provided written
certification (Paragraph IV certification) to FDA that the claims of the 050 Patent are
invalid and/or will not be infringed by the manufacture, use, or sale of Defendants generic
version of Minastrin
24 Fe.
20. By letter dated April 24, 2014, Defendants counsel gave written notice of the
certification of invalidity and/or noninfringement of the 050 Patent, alleging that the
claims of the 050 Patent are invalid due to obviousness, indefiniteness, and lack of
enablement, and that claims 18, 36, and 54 are not infringed by Defendants generic
5

Minastrin
24 Fe product. The letter additionally informed Warner Chilcott that

Defendants seek to engage in the commercial manufacture, use, and sale of a product
bioequivalent to Minastrin
24 Fe prior to the expiration of the 050 Patent.

21. Lupin Atlantis has infringed the 050 Patent under 35 U.S.C. 271(e)(2)(A)
by virtue of submitting ANDA No. 206287 with a Paragraph IV certification and seeking
FDA approval of ANDA No. 206287 prior to the expiration of the 050 Patent. Moreover, if
Lupin Atlantis commercially manufactures, uses, offers for sale, or sells in the United
States, or imports into the United States, Defendants generic version of Minastrin
24 Fe,
it would further infringe the 050 Patent under 35 U.S.C. 271(a), (b), and/or (c). Upon
approval of ANDA No. 206287, Lupin Atlantis will actively induce and/or contribute to
infringement of the 050 Patent under 35 U.S.C. 271(b) and/or (c).
22. Lupin Pharmaceuticals and Lupin Ltd. are jointly and severally liable for any
infringement of the 050 Patent by virtue of submitting ANDA No. 206287 through their
agent, affiliate, and alter-ego Lupin Atlantis. Upon information and belief, Lupin
Pharmaceuticals and Lupin Ltd. contributed to, aided, abetted, and/or induced the
submission of ANDA No. 206287 and its Paragraph IV certification to FDA. Additionally,
upon information and belief, Lupin Pharmaceuticals will market and/or distribute
Defendants generic version of Minastrin
24 Fe if ANDA No. 206287 is approved by FDA.

23. Lupin Pharmaceuticals and Lupin Ltd.s participation in, contribution to,
aiding, abetting, and/or inducement of the submission of ANDA No. 206287 and its
Paragraph IV certification to FDA constitute infringement of the 050 Patent under 35
6

U.S.C. 271(e)(2)(A). Moreover, if Lupin Pharmaceuticals and/or Lupin Ltd. commercially
manufacture, use, offer for sale, or sell within the United States, or import into the United
States, Defendants generic version of Minastrin
24 Fe, they would further infringe the

050 Patent under 35 U.S.C. 271(a), (b), and/or (c). Upon approval of ANDA No. 206287,
Lupin Pharmaceuticals and Lupin Ltd. will actively induce and/or contribute to
infringement of the 050 Patent under 271(b) and/or (c).
24. This case is an exceptional one, and Warner Chilcott is entitled to an award
of its reasonable attorneys fees under 35 U.S.C. 285.
25. Warner Chilcott will be irreparably harmed if Defendants are not enjoined
from infringing or actively inducing or contributing to infringement of the 050 Patent.
Warner Chilcott does not have an adequate remedy at law.
PRAYER FOR RELIEF
WHEREFORE, Warner Chilcott respectfully requests the following relief:
A. A judgment that Defendants have infringed one or more claims of the 050
Patent by submitting ANDA No. 206287;
B. A permanent injunction restraining and enjoining Defendants, their officers,
agents, servants, employees, parents, subsidiaries, divisions, affiliates, and those persons
in active concert or participation with any of them, from making, using, selling, offering to
sell, or importing any product that infringes the 050 Patent, including the product
described in ANDA No. 206287;
7

C. A judgment declaring that making, using, selling, offering to sell, or
importing the product described in ANDA No. 206287, or inducing or contributing to such
conduct, would constitute infringement of the 050 Patent by Defendants pursuant to 35
U.S.C. 271(a), (b), and/or (c);
D. An order that the effective date of any approval of Defendants ANDA be a
date that is not earlier than the expiration of the 050 Patent or any later expiration of
exclusivity to which Warner Chilcott is or becomes entitled;
E. A finding that this is an exceptional case, and an award of attorneys fees in
this action pursuant to 35 U.S.C. 285;
F. Costs and expenses in this action; and
G. Such other and further relief as the Court may deem just and proper.

8

Dated: June 6, 2014 Respectfully submitted,

/s/ Benjamin C. Block
George F. Pappas (D. Md. Bar No. 15339)
Jeffrey B. Elikan (D. Md. Bar No. 26179)
Benjamin C. Block (D. Md. Bar No. 15811)
Eric R. Sonnenschein
Erica N. Andersen
Sumon S. Dantiki
Jeremy D. Cobb
COVINGTON & BURLING LLP
1201 Pennsylvania Avenue, NW
Washington, DC 20004
Tel. (202) 662-6000
Fax. (202) 662-6291
bblock@cov.com

EXHIBIT A
u 7342803
.
UNITED STATES DEPARTMENT OF COMMERCE
United States Patent and Trademark Office
February 24, 2012
THIS IS TO CERTIFY THAT ANNEXED HERETO IS A TRUE COPY FROM
THE RECORDS OF THIS OFFICE OF:
U.S. PATENT: 6,667,050
ISSUE DATE: December 23, 2003
By Authority of the
Under Secretary of Commerce for Intellectual Property
and Director of the United States Patent and Trademark Office
c:Jtaw
T. LAWRENCE
Certifying Officer
(12) United States Patent
Boissonneault et al.
(54) CHEWABLE ORAL CONTRACEPTIVE
(75) Inventors: Roger M. Boissonneault, Long Valley,
NJ (US); Tina M. deVries, Long
Valley, NJ (US)
(73) Assignee: Galen (Chemicals) Limited,
Dunlaoghaire (IE)
( *) Notice: Subject to any disclaimer, the term of this
patent is extended or adjusted under 35
U.S.C. 154(b) by 0 days.
(21) Appl. No.: 09/879,028
(22) Filed: Jun. 12, 2001
Related U.S. Application Data
(63) Continuation-in-part of application No. 09/286,908, filed on
Apr. 6, 1999.
(51) Int. Cl.
7
........... A61K 47/00
(52) U.S. Cl .............. ......... 424/439; 424/400; 424/440;
424/441; 424/464; 424/484; 424/489; 514/841;
514/843
(58) Field of Search ................... .............. 424/400, 439,
424/440, 441, 464, 484, 489; 514/841,
843
11 m 111111111111111111111111111111111111
US006667050Bl
(10) Patent No.: US 6,667,050 Bl
Dec. 23, 2003 (45) Date of Patent:
(56) References Cited
U.S. PAIENT DOCUMENTS
3,960,911 A
4,036,983 A
4,038,413 A
4,136,162 A
4,512,986 A
4,684,534 A
5,135,744 A
5,569,456 A
5,576,014 A
5,747,480 A
6/1976 Suschitzky et al.
7/1977 Rutherford et al.
7/1977 Suschitzky et al.
1/1979 Fuchs et al.
4/1985 Reel et al.
8/1987 Valentine
8/1992 Alexander et al.
10/19% Gorinskyt
11/19% Mizumoto et al.
5/1998 Gast ...................... .... 514/170
* cited by examiner
Primary Examiner-Thurman K. Page
Assistant Examiner--Olaresse Evans
(74) Attorney, Agent, or Firm-Akin,
Hauer & Feld, L.L.P.
(57) ABSTRACT
Gump, Strauss,
The present invention relates to a chewable, palatable oral
contraceptive tablet, comprising an oral contraceptive agent,
a chewable carrier suitable for human consumption, and not
comprising a ferrocene compound, as well as use of these
tablets in a method of human female oral contraception, and
in a method of enhancing compliance with a human female
oral contraceptive regimen.
60 Clalms, No Drawings
__
US 6,667,050 Bl
1
CHEWABLE ORAL CONTRACEPTIVE
CROSS-REFERENCE TO RELATED
APPUCMIONS
This is a continuation-in-part of U.S. patent application
Ser. No. 09/286,908, filed Apr. 6, 1999.
STATEMENT REGARDING FEDERALLY
SPONSORED RESEARCH OR DEVELOPMENT
Not Applicable.
REFERENCE TO MICROFICHE APPENDIX
Not Applicable.
BACKGROUND OF THE INVENTION
The present invention generally relates to an oral contra-
ceptive delivery system, and in particular an oral contracep-
tive delivery system involving novel alternate dose forms to
improve compliance.
The efficacy of oral contraceptives tends to be particularly
patient compliance dependent, largely due to the lack of a
disease state or symptoms to remind a human female patient
(sometimes referred to simply as "patient" or "woman") to
take a pill. The single most significant reason for failure with
oral contraceptives is use, rather than method, failure. That
is, unless the contraceptives are used according to the
prescribed regimen, the contraceptives can fail to effectively
help a patient avoid pregnancy. Further, in order to be most
effective in preventing pregnancy and maintaining men-
strual cycle control, proper compliance with an oral contra-
ceptive dosage regimen requires that the oral contraceptives
be taken at about the same time each day.
2
to conceal, they are not necessarily easy to ingest. Access to
water to facilitate contraceptive pill taking remains a prob-
lem. Most medications are typically stored in a medicine
cabinet and therefore are likely to be near a water source. On
5 the contrary, oral contraceptive pills are often carried on the
person and a source of water is not always available when
it is time to take the oral contraceptive pill. Additionally, a
certain segment of the patient population will have trouble
10
IS
swallowing pills, irrespective of access to water.
The present invention provides an improved oral contra-
ceptive tablet. The technology encompassed in the invention
involves a chewable, palatable oral contraceptive tablet that
has appropriate size and hardness for blister packaging and
compliant use.
BRIEF SUMMARY OF THE INVENTION
One aspect of the present invention relates to a chewable,
palatable oral contraceptive tablet, comprising an oral con-
20 traceptive agent, a chewable carrier suitable for human
consumption, and not comprising a ferrocene compound.
Another aspect of this invention relates to a method of
human female oral contraception, the method comprising
providing a chewable, palatable oral contraceptive tablet
25
comprising a contraceptively effective amount of an oral
contraceptive agent, and a chewable carrier suitable for
human consumption, and not comprising a ferrocene
compound, and administering the tablet to a human female.
Yet another aspect of this invention relates to a method of
30 enhancing compliance with a human female oral contracep-
tive regimen involving oral contraceptive tablets, the
method comprising providing chewable, palatable oral con-
traceptive tablets comprising a contraceptively effective
amount of an oral contraceptive agent, and a chewable
35 carrier suitable for human consumption, and not comprising
a ferrocene compound, and administering the tablets to the
human female in accordance with the contraceptive regi-
men.
Various attempts have been made to improve patient
compliance with contraceptive regimens. For example, it has
been suggested that progestin rods can be inserted subder-
mally. This procedure has been described, for example, in
U.S. Pat. No. 5,756,115. This technique has the significant
disadvantage of requiring a surgical incision, a procedure
40
that is highly disfavored by a relatively large segment of the
patient population.
BRIEF DESCRIPTION OF THE SEVERAL
VIEWS OF THE DRAWINGS
Not Applicable.
As another example, it has been suggested that DEPO-
PROVERA (Pharmacia, Inc.) medroxyprogesterone
acetate can be injected subcutaneously every three months.
45
This technique has been described, for example, in U.S. Pat.
No. 4,639,439. This procedure has the disadvantage of
requiring an injection via hypodermic needle, which is also
a procedure that is disfavored by many patients.
50
In many cases, the patient prefers to carry the contracep-
tive pills on her person as a matter of lifestyle or personal
discretion. This is especially true for younger patients, and
it is not uncommon for such patients to exchange pills.
Members of this population tend to view portable packaging
55
of the pills, immediate access to the pills, and ease of pill use
as significant benefits.
Prior proposed solutions to the compliance problem have
tended to focus primarily or exclusively on optimizing
compliance packaging, rather than on changes to the dosage 60
form. It has been suggested that instead of being packaged
DETAILED DESCRIPTION OF THE
INVENTION
The present invention relates to chewable, palatable oral
contraceptive tablets for administering an oral contraceptive
agent to human females. The tablets of this invention may
simply be chewed, and therefore are easy for a patient to
ingest, even in the absence of a liquid. The oral contracep-
tive agent formulation of this invention improves dosage
regimen compliance, and thereby enhances the desired con-
traceptive effect of the oral contraceptive. This invention
also includes methods for administering the oral contracep-
tive formulations to a woman.
Definitions
The articles "a" and " an" are used herein to refer to one
or more than one (i.e., to at least one) of the grammatical
objects of the article. By way of example, "an element"
means one element or more than one element.
in vials, contraceptive pills can be packaged in 21 or 28 day
blister packages. It has also been suggested that the size of
these packages can be reduced to improve portability and
confidentiality.
The term "oral contraceptive agent," as used herein, refers
to any compound or combination of compounds which,
65 when administered orally, prevents pregnancy.
Although oral contraceptive pills provided in a small
blister package are somewhat more convenient to carry and
The term "estrogen," as used herein, refers to any natural
or synthetic compound which exlubits an effect on the
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US 6,667,050 Bl
3
female reproductive organs in a manner similar to the natural
female hormone estrogen. Examples of an estrogen include,
but are not limited to, ethinyl estradiol, estradiol, estradiol
valerate, and estradiol acetate.
The term "progestin," as used herein, refers any natural or
synthetic compound which exhibits a progestational effect
5
4
levonorgestrel, ethynodiol diacetate, norgestrel,
norgestimate, gestodene, drospirenone, trimegestone,
levodesogestrel, gestodyne, and nesterone. Preferably, the
progestin is norethindrone.
on the female reproductive organs. Examples of a progestin
include, but are not limited to, norethindrone, norethindrone
acetate, desogestrel, levonorgestrel, ethynodiol diacetate, 10
norgestrel, norgestimate, gestodene, drospirenone,
trimegestone, levodesogestrel, gestodyne and nesterone.
The dosage of the oral contraceptive agent employed
would tend to be that conventionally used in the art for the
particular oral contraceptive agent selected. The proportion
of the oral contraceptive agent in the tablet may be a
pharmaceutically effective trace amount to about 10% by
weight. Thus, the quantity of oral contraceptive agent per
tablet may be varied as desired, typically about 10 micro-
grams to about 5 milligrams, but the lower and upper
dosages may be reduced or increased. Examples of approxi-
mate dosage ranges of oral contraceptive agents in milli-
grams per tablet are summarized in Table 1.
The term "palatable," as used herein, means that the tablet
of this invention has a taste, mouth feel, chewability, texture,
aroma, and lack of grittiness and bad aftertaste that makes
15
the tablet agreeable to a woman to chew.
TABLE 1
Ennmles of Dose Ranges of 011!1 Contracptive Ments Cmilli&!'l!ms por tablet)
Description Examples Broad Intermediate Preferred
Progestin
Estrogen
A tablet is "chewable," as used herein, such that when the
tablet is chewed, it breaks into smaller pieces that can be
swallowed. This is in contrast to gum, for example, which
does not break into smaller pieces when chewed.
Description of the Invention
The first aspect of the invention relates to a chewable,
palatable oral contraceptive tablet comprising an oral con-
traceptive agent, a chewable carrier suitable for human
consumption and not compr'.sing a ferrocene compound.
The tablet of this invention expressly does not contain a
ferrocene compound. Ferrocene compounds are used in the
treatment of anemia and it should not be assumed that all
patients desiring an oral contraceptive agent are anemic.
Administering ferrocene compounds when they are not
needed can lead to iron poisoning. Additionally, ferrocene
compounds may not be palatable when chewed.
In principle, virtually any oral contraceptive agent used in
human medicine could be employed in accordance with the
principles of the present invention. The oral contraceptive
agent may be an estrogen, a progestin, or a combination of
an estrogen and a progestin. In one embodiment, the oral
contraceptive agent is an estrogen selected from the group
consisting of ethinyl estradiol, estradiol, estradiol valerate,
and estradiol acetate. Preferably, the estrogen is ethinyl
estradiol.
Norethindrone, 0.1 to 2.5 0.25 to 2.0 0.4 to 1.5
Norethindrone acetate 0.1 to 2.5 0.25 to 2.0 0.4 to 1.5
Desogestrel 0.05 to 0.5 0.1 to 0.3 0.1 to 0.2
Levonorgestrel 0.025 to 1.5 0.025 to 1.0 0.05 to 0.6
Ethynodiol diacetate 0.5 to 2.5 0.75 to 1.25 0.9 to 1.1
Norgestrel 0.05 to 3.0 0.05 to 2.0 0.1 to 1.2
Norgestimate 0.1 to 0.5 0.15 to 0.35 0.18 to 0.25
Gestodene O.Q3 to 0.15 0.05 to 0.10 0.06 to 0.075
Drospirenone 1.0 to 5.0 2.0 to 4.0 2.5 to 3.5
Trimegcstone 0.05 to 0.5 0.1 to 0.3 0.1 to 0.2
Ethinyl Estradiol, 0.01 to O.Q75 O.Q15 to 0.05 0.020 to 0.050
Estradiol 0.5 to 4.0 lto3 1.5 to 2.5
Estradiol valerate 0.5 to 5.0 1.5 to 3.5 1.9 to 3.0
Estradiol acetate 0.5 to 5.0 1.5 to 3.5 1.8 to 3.0
In one preferred embodiment, the tablet comprises estro-
gen in the form of ethinyl estradiol in an amount of about 10
micrograms to about 75 microgranlS. In another preferred
40 embodiment, the tablet comprises progestin in the form of
norethindrone in an amount of about 0.1 milligram to about
2.5 milligrams.
The invention also includes a tablet in which the oral
contraceptive agent is a combination of an estrogen and a
45 progestin. Preferably, the estrogen is ethinyl estradiol and
the progestin is norethindrone. In a more preferred
embodiment, the amount of ethinyl estradiol in the tablet is
about 10 micrograms to about 75 micrograms and the
amount of norethindrone in the tablet is about 0.1 milligram
50
to about 2.5 milligrams.
The tablets of this invention can be used in conjunction
with an oral contraceptive regimen. The regimen can com-
prise administering tablets on a daily basis for multiple
consecutive days. As such, throughout the duration of the
55
regimen the amount of oral contraceptive agent in the oral
contraceptive tablets may remain constant, thereby compris-
ing a uniphasic regimen. Additionally, the amount of oral
contraceptive agent in the oral contraceptive tablets may
vary throughout the duration of the regimen, thereby com-
prising a multiphasic regimen. In tablets comprising an
60 estrogen and a progestin, the ratio of the estrogen to the
progestin can be constant throughout the duration of the
regimen. Additionally, the ratio of the estrogen to the proges-
tin in the oral contraceptive tablets can vary throughout the
regimen.
In another embodiment, the oral contraceptive agent is a 65
progestin selected from the group consisting of
norethindrone, norethindrone acetate, desogestrel,
It is also possible to form placebo tablets which otherwise
correspond in composition to the tablet of the present
invention but are free of the oral contraceptive agent
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US 6,667,050 Bl
5
The oral contraceptive agent may be present in a carrier
either in a dissolved or a uniformly suspended state. A
carrier comprises all but the active oral contraceptive agent
or agents and includes an inactive ingredient or a combina-
tion of one or more inactive ingredients. The carrier imparts
chewable and palatable characteristics to the tablet and must
Ingre-
dient
6
TABLE 2-continued
Sweetener and Flavor Amounts Used in Chewable Om!
Contraceptive Formulations
10
be suitable for human consumption, that is, free of harmful
amounts of any toxins or components that are adverse to
humans. All ingredients in the carrier should be generally
recognized as safe (GRAS), as determined by the Food and
Drug Administration (FDA) or the Flavor and Extract Manu-
facturers' Association (FEMA). The carrier selected for the
invention must be chewable and should not confer a dis-
agreeable taste to the tablet. Thus, the carrier itself must be 15
palatable. The primary ingredient of a carrier is one or more
diluents. Non-limiting examples of diluents that can be used
Type Examples Broad Intermediate Preferred
Flavor Spearmint 0.5 to 5% 1 to 3% 1.5 to 2.5%
Agent Winter- 0.5 to 5% 1 to 3% 1.5 to 2.5%
green
Wild berry 0.1 to 3% 0.2 to 1% 0.3 to 0.5%
Optionally, a color agent may be added to aid in tablet
identification and to enhance the visual appearance of the
tablet. A visually pleasing color enhances patient acceptance
and thereby compliance with an oral contraceptive regimen.
The color agent may be any that are well known to those in
the tablet-making art in view of the present disclosure, and
in accordance with this invention include microcrystalline
cellulose, com starch, modified starch, calcium carbonate,
dicalcium phosphate, and poly-alcohol sugars such as
20
dextrose, maunitol, sorbitol, xylitol, lactose, sucrose, and
fructose. Many other diluents or other ingredients suitable as
components of carriers for a chewable, palatable oral con-
traceptive tablet are available and would be well known to
25
those skilled in the art in view of the present disclosure.
could be used in any amount to impart the desired color.
The tablet can be manufactured by standard pharmaceu-
tical techniques of solid dose formulation, such as granula-
tion and compression. These processes are well known to
those skilled in the art of making tablets (See Lieberman,
Lachman, and Schwartz, Pharmaceutical Dosage Fonns,
Volume 1, New York, 1989). During the granulation process,
other ingredients typically used in tablet formulation for
human consumption can be included, such as binders,
lubricants, anti-adherents, glidants, disintegrants and fillers
In another aspect of the invention, the tablet optionally
further comprises at least one of a flavor agent, a sweetener,
and a color agent. A flavor agent can be used to enhance the
taste of the tablet, making the tablet more palatable than a
tablet without a flavor agent. Spray dried flavor agents are
preferred because they are easy to incorporate into a chew-
able tablet. Non-limiting examples of preferred flavor agents
impart the following flavors: strawberry, wild berry,
spearmint, wintergreen, black cherry, orange, orange cream,
and lemon. The flavoring agents are readily available from
many commercial sources. Exemplary compounds suitably
used in preparing flavors are listed in G. Burdock, Ed.,
Fenaroli's Handbook of Flavor Ingredients, 3m edition,
Volumesl and II, CRC Press, New York, 1995. Other flavors
and flavoring agents suitable for the tablet would be well
known to those skilled in the art in view of the present
disclosure.
A sweetener can also be used to enhance to taste of the
tablet, making the tablet more palatable than a tablet without
a sweetener. Sweeteners include natural sugars and artificial
sugar substitutes. Non-limiting examples of sweeteners that
can be used in accordance with this invention include
aspartame, sucralose, xylitol, soroitol, mannitol, dextrose,
sucrose, and fructose. Non-limiting examples of the amount
of flavor agents or sweeteners that can be used in the tablet
composition of the present invention are listed in Table 2.
The amounts in Table 2 are given as percentage of the total
tablet weight.
Ingre-
dient
Type
Sweet-
ener
TABLE 2
Sweetener and Flavor Amounts Used in Chewable Oral
Omtmceptjvs FormultiOJJs
Examples Broad Intermediate l'Teferred
Aspartame 0.02 to 1.0% 0.02% to 0.2% 0.03% to 0.05%
Sucralose 0.01 to 0.5% 0.01% to 0.1% 0.02 to 0.04%
30
or other optional ingredients that do not adversely affect
chewability or palatability of the tablet or its active oral
contraceptive agent ingredient(s).
Binders aid the formation of granulated particles of active
35
oral contraceptive agents and carrier ingredients. Non-
limiting examples of binders include glucose, acacia, guar
gum, gelatin, simple syrup, sucrose, sorbitol, starch, alginic
acid, alginate salts, polyethylene glycol,
polyvinylpyrrolidone, polymethacrylates, pregelatinized
40
starch, and celluloses such as methylcellulose, sodium
carl>oxymethylcellulose, hydroxypropylmethylcellulose,
hydroxypropylcellulose, and ethylcellulose. A solution of
binder is prepared (concentrations dependent on the particu-
lar binder used), and the binder solution is mixed with the
45
other excipients to form the wet granulation. A binder such
as polyvinylpyrrolidone (Povidone) is typically used in a
solution of about 3% to about 15% by weight and is added
to the other tablet ingredients resulting in a final formulation
concentration of about 2% to about 5%. Similarly, cellulose
50
derivatives are typically used in granulating solutions of
about 5% to about 10% by weight and concentrations would
be known to one skilled in the art of making tablets using
wet granulation in view of the present disclosure.
Disintegrants facilitate breakup of the tablet after admin-
55 istration during chewing. Non-linliting examples of disinte-
grants include crospovidone, croscarmellose sodium,
starches, com starch, potato starch, modified corn starch,
sodium starch glycolate, and pregelatinized starch. Disinte-
grants can be included in the tablet formulation in amounts
60
generally less than about 25% of the tablet weight, prefer-
65
ably less than about 20%, and more preferably about 1 to
about 20% (natural starches such as com or potato starch),
about 5 to about 10% (pregelatinized starch), and about 3 to
8% (modified com starch). Crospovidone and croscarmel-
lose sodium are used at levels of about 5% or lower.
As a final step in the manufacture of the tablet, a lubricant,
an anti-adherent, and a glidant can be added to the tablet
US 6,667,050 Bl
7
granulation. A lubricant facilitates tablet manufacture by
reducing friction in the tablet die during compression and
ejection. An anti-adherent prevents the tablet from sticking
to the tablet punch and die wall. A glidant improves ftow
characteristics of the granulation. Non-limiting examples of s
a lubricant include stearates, such as magnesium, calcium,
and sodium stearates, stearic acid, hydrogenated vegetable
oils, waxes, talc, boric acid, sodium benzoate, sodium
acetate, sodium chloride, DL-leucine, sodium oleate,
sodium lauryl sulfate, magnesium lauryl sulfate, and CAR- 10
BOWAX (Union Carbide Chemicals & Plastics Technol-
ogy Corp.) polyethylene glycols. Non-limiting examples of
an anti-adherent include talc, com starch, colloidal silicon
dioxide, DL-leucine, sodium lauryl sulfate, and metallic
stearates. Non-limiting examples of a glidant include talc, 15
com starch, and colloidal silicon dioxides such as CAB-0-
SIL (Cabot Corp.), SYLOID (W.R. Grace & Co.), and
AEROSIL (Degussa). Some ingredients, such as talc, can
contribute to the formulation with combined functions,
acting as a lubricant, and an anti-adherent, and a glidanl 20
A lubricant is typically included in the tablet formulation
in amounts less than about 10% of the tablet weight,
preferably less than about 6%, and more preferably about
0.25 to about 2% (stearates, stearic acid, hydrogenated
vegetable oil), about 1 to about 5% (talc, waxes, DL-leucine, 25
CARBO WAX, sodium lauryl sulfate), about 1 to about 2%
(magnesium lauryl sulfate) and about 4 to about 6% (sodium
chloride, sodium oleate, sodium benzoate, sodium acetate).
Anti-adherents are typically included in the tablet formu-
lation in amounts generally less than about 15% of the tablet
30
weight, preferably less than about 12%, and more preferably
about 3 to about 10% (cornstarch, DL-leucine), about 1 to
about 5% (talc), about 0.1 to about 0.5% (colloidal silicon
dioxide) and less than about 1% (sodium lauryl sulfate,
metallic stearates ). 35
A glidant is typically included in the tablet formulation in
amounts generally less than about 15% of the tablet weight,
preferably less than about 12%, and more preferably less
than about 5 to about 10% (com starch), about 0.1 to about
40
0.5% (CAB-0-SIL, SYLOID), about 1 to about 3%
(AEROSIL), and about 5% (talc).
8
The hardness of the tablet may be any hardness that
allows for tablet formation and that is still palatable and
chewable. One aspect of the invention includes a tablet
having a hardness sufficient for blister packaging while still
remaining palatable and chewable. Blister packaging is
common in the art of oral contraceptive tablet dispensing. In
a preferred embodiment, the tablet of the invention has a
hardness of about 5 kilopond (kp) to about 15 kp, and
preferably about 7 kp to about 12 kp.
human female oral contraception comprising providing a
chewable, palatable oral contraceptive tablet comprising a
contraceptively effective amount of an oral contraceptive
agent, and a chewable carrier suitable for human
consumption, and not comprising a ferrocene compound,
and administering the tablet to a human female. The tablet
is the tablet described above, and typically and preferably, a
number of such tablets as part of a contraceptive regimen.
The tablet can be administered to the woman in a variety
of ways. Typically, the tablet is administered once daily. The
tablet routinely contains a contraceptively active amount of
an oral contraceptive agent, and some tablets used in a
regimen may be a placebo. The placebo tablets are admin-
istered on days where the oral contraceptive agent is not
required. As such, the woman is administered a tablet every
day to help maintain the contraceptive regimen of taking a
daily tablet. For example, a dosage regimen may utilize
about 21 to about 63 days of tablets containing the oral
contraceptive agent followed by about 3 to about 7 days of
tablets comprisiog a placebo. Preferably, the regimen entails
administering tablets for total of about 24 to about 32 days,
wherein tablets containing the oral contraceptive agent are
administered for about 21 to about 25 days, followed by
about 3 to about 7 days of placebo tablets not containing the
contraceptive. In one preferred embodiment, the tablets are
administered for a total of about 28 days.
As explained above, the contraceptive dosage in the
tablets can be uniphasic or multiphasic.
enhancing compliance with a human female oral contracep-
tive regimen involving oral contraceptive tablets, the
method comprising providing chewable, palatable oral con-
traceptive tablets comprising a contraceptively effective
The chewable tablet generally is not coated with a film or
sugar coating. However, thin tablet coatings of a type known
to those skilled in making coated tablets can be used.
45
carrier suitable for human consumption, and not comprising
a ferrocene compound, and administering the tablets to the
human female in accordance with the contraceptive regi-
men.
In one preferred embodiment of the invention, the oral
contraceptive agent comprises norethindrone and ethinyl
estradiol, the carrier comprises dicalcium phosphate, lactose
monohydrate, and maltodextrin, and the tablet further com-
prises sucralose, a ftavor agent, sodium starch glycolate, so
povidone, and magnesium stearate.
The overall size of the tablet may be any tablet size that
incorporates the desired contraceptively effective amount of
the oral contraceptive agent and the carrier and is still
chewable and palatable. In a preferred embodiment, the size 55
of the tablet is small, on the order of about 50 milligrams to
about 300 milligrams. More preferably, the tablet weight is
about 70 milligrams to about 120 milligrams, and most
preferably, the tablet weight is about 90 milligrams to about
110 milligrams. A smaller tablet is more portable than a 60
larger tablet and therefore more appealing to patients pre-
ferring to carry oral contraceptive pills on their person,
particularly in blister packaging. Further, smaller tablets are
more likely than larger tablets to be accepted as chewable.
Therefore, smaller tablets are more likely to enhance a 65
patient's compliance with an oral contraceptive regimen.
The shape of the tablet of the present invention is not critical.
In connection with this aspect of the invention, each tablet
of the regimen preferably comprises a daily dosage of the
oral contraceptive agent. As such, daily administration of
one of the tablets would be part of the regimen. The
chewable, palatable oral contraceptive of this invention
allows the woman the convenience of ingesting the tablet in
a manner that does not require taking the tablet with liquid,
without chewing it. Therefore, the woman can take the tablet
each day at a time and place that is suitable to her lifestyle.
Ingesting the tablets at the same time of day on a daily basis
enhances compliance with any given contraceptive regimen.
The regimen can comprise any number of days of admin-
istration of the tablets to the woman. In one preferred
embodiment, the regimen comprises providing about 21 to
about 63 tablets, each tablet comprising the daily dosage of
the oral contraceptive agent, followed by about 3 to about 7
tablets, each comprising a placebo. Preferably, a total of
about 24 to about 32 tablets are administered daily, wherein
US 6,667,050 Bl
9
about 21 to about 25 tablets each comprising the oral
contraceptive agent are administered, followed by about 3 to
about 7 tablets each comprising a placebo. In one preferred
embodiment, a total of about 28 tablets is administered.
Ingredient
Sweetener
Flavor Agent
Disintegrant
10
EXAMPLE 1-continued
Composition of a 90 milligram tablet
Ingredient
Sucralose
Spearmint
Amount
(milligrams/tablet)
The amount of the oral contraceptive agent through the
duration of the regimen can remain constant or can be varied
for tablets containing an oral contraceptive agent (rather
than placebo tablets without an oral contraceptive agent). In
one embodiment, the amount of the oral contraceptive agent
is present in the same amount in the oral contraceptive
tablets of the regimen, thereby comprising a uniphasic
regimen. In another embodiment, the amount of the oral
10 Binder
Sodium starch glycolate
Povidone
0.02
1.8
4.1
1.5
0.41 Lubricant Magnesium 6tearate
One technique of making the tablets of the present inven-
tion is a wet granulation technique. In a wet granulation
technique, the active oral contraceptive agents are blended in
a solution of binder which is then blended with the diluent(s)
to form a wet granulation. After drying, the granulation is
contraceptive agent is present in varying amounts in the oral
contraceptive tablets of the regimen, thereby comprising a
multiphasic regimen. In tablets comprising an estrogen and 15
a progestin, the ratio of the estrogen to the progestin can be
constant throughout the duration of the regimen.
Alternatively, the ratio of the estrogen to the progestin in the
tablets can vary throughout the regimen.
20
blended with the flavor ingredient(s), the disintegrant, the
lubricant and any other optional ingredients. The final blend
is compressed into tablets. This wet granulation method is
exemplified by Examples 1 and 2.
Any number of the tablets may be dispensed in any type
of packaging commonly used in the art of tablet dispensing.
Blister packages are often and preferably used for dispens-
ing oral contraceptives. Blister packages are generally small
and portable, usually and preferably containing the number
of tablets required for a month of dosing. Many patients
25
desiring oral contraceptive tablets find this method of dis-
pensing convenient. In a preferred embodiment, the tablets
for the oral contraceptive regimen of this invention are
dispensed in a blister package. The packaging is preferably
in the form of a 28-daily dosage units blister package
30
comprising about 21 to about 25 tablets comprising the oral
contraceptive agent and the remaining respective about 7 to
about 3 tablets comprising a placebo.
Alternatively, a dry granulation technique can be used. In
a dry granulation technique, the active oral contraceptive
agents are blended with the diluent(s) to form a dry granu-
lation. This is then blended with the flavor ingredient(s), the
lubricant and any other optional ingredients, and finally
compressed into tablets. This dry granulation method is
exemplified by Examples 3, 4 and 5.
Alternatively, the active pharmaceutical ingredients are
wet granulated as described previously, then blended with
35 additional diluent(s) to form a dry granulation. This is then
blended with the flavor ingredients, the lubricant and any
other optional ingredients, and finally compressed into tab-
lets. This method is exemplified by Example 6.
A tablet made in accordance with the present invention
may simply be chewed. This substantially reduces the exist-
ing barriers to compliance. The use of a chewable, palatable
tablet in accordance with the present invention eliminates
the need to incorporate liquid to facilitate swallowing and
makes oral contraceptives more agreeable for patients who
40
have difficulty or reluctance to swallowing tablets. The
chewable, palatable tablets of this invention have a tablet
size aod hardness suitable for use in blister packaging and
EXAMPLE2
are synergistic with the existing design and intent of oral Amount
contraceptive package portability and convenience.
45
_lngredie __ _ ___
1
_sr_ed_
10
_ _t ______ <_mil _. _Hgra _ ms _ fm_b_le..;. t)_
Therefore, the oral contraceptive formulations of this Oral Contraceptive Agent Norethindrone 0.40
invention, administered according to this invention, provide Oral Contraceptive Agent Ethinyl Estradiol 0.035
a method of enhancing compliance with a human female Diluent Dicalcium Phosphate 40.8
oral contraceptive regun en. Diluent Lactose Monohydrate 40.8
Diluent Maltodextrin 0.36
The invention will now be described in more detail with so Sweetener Aspartame 0.04
reference to the following specific, non-limiting examples. Flavor Agent Spearmint 1.8
Disintegrnnt Sodium starch glycolate 4.11
Compositions that have been prepared in accordance with Binder Povidone 1.54
this invention are given in Examples 1-2. Additional Lubricant Magoesium stearnte 0.41
examples of compositions that can be formulated in accor-
dance with this invention are given in Examples 3-6.
EXAMPLE 1
Amount
Ingredient (milligrams/tablet)
Oral Contraceptive Agent Norethindrone 0.40
Oral Contraceptive Agent Ethinyl Estradiol 0.035
Diluent Dicalcium Phosphste 40.8
Diluent lactose Monohydrate 40.8
Diluent Maltodextrin 0.16
55
60
65
EXAMPLE3
Amount
Ingredient (milligrams/tablet)
Diluent Dextrose 97
Flavor Agent Spearmint 2
Luhricant Magnesium stearate o.s
US 6,667,050 Bl
11
EXAMPLE4
Ingredient Type
Oral Contraceptive Agent
Oral Contraceptive Agent
Diluent
Flavor Agent
Lubricant
Ingredient
Norethindrone
Ethinyl Estradiol
Mannitol
Strawberry
Magnesium stearate
EXAMPLE6
Amount
(milligrams/tablet)
0.40
0.035
97
2
0.5
Amount
Ingredient TYPe Ingredient (milligrams/tablet)
Diluent Dextrose 60
Diluent Lactose 37
Flavor Agent Strawberry 2
Lubricant Magnesium stearate 0.5
EXAMPLE6
Ingredient TYPe Ingredient
Oral Contraceptive Agent Norethindrone
Oral Contraceptive Agent Ethinyl Estradiol
Diluent Dicalcium Phosphate
Diluent lActose Monohydrate
Diluent Dextrose
Diluent Maltodexuin
Sweetener Sucralose
Flavor Agent Spearroint
Disintegrant Sodium starch glycolate
Binder Povidone
Lubricant Magnesium stearate
Amouot
(milligrams/tablet)
0.40
0.035
20.8
20.8
70
0.16
0.02
1.8
4.1
1.5
0.41
12
5. The tablet of claim 1, wherein the oral contraceptive
agent comprises an estrogen.
6. The tablet of claim 5, wherein the estrogen is selected
from the group consisting of ethinyl estradiol, estradiol,
5 estradiol valerate, and estradiol acetate.
7. The tablet of claim 6, wherein the carrier is selected
from the group consisting of dicalcium phosphate, lactose,
corn starch, microcrystalline cellulose, maltodextrin,
dextrose, mannitol, sorbitol, xylitol, fructose, sucrose, and
10 calcium carbonate.
agent comprises a progestin.
9. The tablet of claim 8, wherein the progestin is selected
from the group consisting of norethindrone, norethindrone
15 acetate, desogestrel, levonorgestrel, ethynodiol diacetate,
norgestrel, norgestimate, gestodene, drospirenone,
trimegestone, levodesogestrel, gestodyne, and nesterone.
20
25
calcium carbonate.
agent comprises an estrogen and a progestin.
12. The tablet of claim 11, wherein the estrogen is selected
from the group consisting of ethinyl estradiol, estradiol,
estradiol valerate, and estradiol acetate, and the progestin is
selected from the group consisting of norethindrone, nore-
thindrone acetate, desogestrel, levonorgestrel, ethynodiol
30 diacetate, norgestrel, oorgestimate, gestodene, drospirenooe,
35 dextrose, mannitol, sorbitol, xylitol, fructose, sucrose, and
calcium carbonate.
14. The tablet of claim 13, further comprising at least one
of a flavor agent, a sweetener, and a color agent.
15. The tablet of claim 1, wherein the tablet weighs about
40 50 mi!ligranlS to about 300 milligrams.
16. The tablet of claim 1, wherein the tablet has a hardness
sufficient for blister packaging.
It will be appreciated by those skilled in the art that
changes could be made to the embodiments described above
without departing from the broad inventive concept thereof. 45
It is understood, therefore, that this invention is not limited
17. The tablet of claim 1, wherein the tablet has a hardness
of about 5 kiloponds to about 15 kiloponds.
agent comprises norethindrone and ethinyl estradiol, the
carrier comprises dicalcium phosphate, lactose
prises sucralose, a flavor agent, sodium starch glycolate,
to the particular embodiments disclosed, but it is intended to
cover modifications within the spirit and scope of the present
invention as defined by the appended clainls.
We claim:
1. A chewable, palatable oral contraceptive tablet, com-
prising an oral contraceptive agent, a chewable carrier
suitable for human consumption, wherein the contraceptive
tablet is chewable and palatable and does not contain a
ferrocene compound.
agent is selected from the group consisting of an estrogen,
a progestin, and a combination thereof.
calcium carbonate.
calcium carbonate.
so povidone, and magnesium stearate.
19. A method of human female oral contraception, the
method comprising providing a chewable, palatable oral
contraceptive tablet comprising a contraceptively effective
55 carrier suitable for human consumption, and does not con-
tain a ferrocene compound, and administering the tablet to
a human female.
20. The method of claim 19, wherein the oral contracep-
tive agent is selected from the group consisting of an
60 estrogen, a progestin, and a combination thereof.
21. The method of claim 20, wherein the carrier is
selected from the group consisting of dicalcium phosphate,
lactose, corn starch, microcrystalline cellulose,
maltodextrin, dextrose, mannitol, sorbitol, xylitol, fructose,
65 sucrose, and calcium carbonate.
Copy provided by USPTO from the PIRS Image Database on 0212112012
US 6,667,050 Bl
13
maltodextrin, dextrose, mannitol, smbitol, xylitol, fructose,
sucrose, and calcium carbonate.
14
23. 1be method of claim 19, wherein the oral contracep-
tive agent comprises an estrogen.
5 sucrose, and calcium carbonate.
24. The method of claim 23, wherein the estrogen is
selected from the group consisting of ethinyl estradiol,
estradiol, estradiol valerate, and estradiol acetate.
tive agent comprises an estrogen.
selected from the group consisting of dicalcium phosphate, 10
15
estradiol, estradiol valerate, and estradiol acetate.
tive agent comprises a progestin.
27. The method of claim 26, wherein the progestin is
selected from the group consisting of norethindrone, nore-
diacetate, norgestrel, norgestimate, gestodene, drospirenone,
20 maltodextrin, dextrose, mannitol, sorbitol, xylitol, fructose,
tive agent comprises a progestin.
45. The method of claim 44, wherein the progestin is
tive agent comprises an estrogen and a progestin.
25 selected from the group consisting of norethindrone, nore-
diacetate, norgestrel, norgestimate, gestodene, drospirenone,
estradiol, estradiol valerate, and estradiol acetate, and the 30
progestin is selected from the group consisting of
levodesogestrel, gestodyne, and nesterone.
35
tive agent comprises an estrogen and a progestin.
estradiol, estradiol valerate, and estradiol acetate, and the
32. The method of claim 31, wherein the tablet further
comprises at least one of a flavor agent, a sweetener, and a
color agent.
40 progestin is selected from the group consisting of
33. The method of claim 19, wherein the tablet weighs
about 50 milligrams to about 300 milligrams.
34. The method of claim 19, wherein the tablet has a
hardness sufficient for blister packaging.
hardness of about 5 kiloponds to about 15 kiloponds.
45
levodesogestrel, gestodyne, and nesterone.
50. The method of claim 49, wherein the tablets further
comprise at least one of a flavor agent, a sweetener, and a
color agent.
36. The method of claim 19, wherein the oral contracep- 50
tive agent comprises norethindrone and ethinyl estradiol, the
povidone, and magnesium stearate.
51. The method of claim 37, wherein each tablet weighs
55
about 50 milligrams to about 300 milligrams.
52. The method of claim 37, wherein the tablets have a
hardness sufficient for blister packaging.
37. A method of enhancing compliance with a human
female oral contraceptive regimen involving oral contracep-
tive tablets, the method comprising providing chewable,
palatable oral contraceptive tablets comprising a contracep-
tively effective amount of an oral contraceptive agent, and a 60
chewable carrier suitable for human consumption, and not
comprising a ferrocene compound, and administering the
tablets to the human female in accordance with the contra-
ceptive regimen.
hardness of about 5 kiloponds to about 15 kiloponds.
tive agent comprises norethindrone and ethinyl estradiol, the
tive agent is selected from the group consisting of an
estrogen, a progestin, and a combination thereof.
65 povidone, and magnesium stearate.
55. The method of claim 37, wherein each tablet com-
prises a daily dosage of the oral contraceptive agent.
US 6,667,050 Bl
15
56. The method of claim 55, wherein the regimen com-
prises providing about 21 to about 25 tablets comprising the
oral contraceptive agent.
57. The method of claim 56, wherein the regimen further
comprises about 3 to about 7 tablets comprising a placebo.
58. The method of claim 56, wherein the regimen is a
uniphasic regimen wherein the oral contraceptive agent is
present in the same amount in the tablets.
16
59. The method of claim 56, wherein the regimen is a
multiphasic regimen wherein the oral contraceptive agent is
present in differing amounts in the tablets.
60. The method of claim 37, wherein the tablets are
5
provided in a blister package.
* * * * *
Copy provided by USPTO from the PIRS lma11e Database on 02/21/2012

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Warner Chilcott Company v. Lupin Atlantis Holdings Et. Al.

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IN THE UNITED STATES DISTRICT COURT

FOR THE DISTRICT OF MARYLAND

24 Fe, which contains the active ingredients ethinyl estradiol and

24 Fe was approved by FDA on May 8, 2013, and is

24 Fe and its use in accordance with the FDA-approved labeling

24 Fe before the expiration of the 050 Patent. Defendants

24 Fe product for which

24 Fe product. The letter additionally informed Warner Chilcott that

24 Fe prior to the expiration of the 050 Patent.

24 Fe if ANDA No. 206287 is approved by FDA.

24 Fe, they would further infringe the

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