IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
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`BEFORE THE PATENT TRIAL AND APPEAL BOARD
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`MYLAN PHARMACEUTICALS INC.
`Petitioner
`v.
`WARNER-CHILCOTT COMPANY LLC.
`Patent Owner
`
`U.S. Patent No. 7,704,984 to Boissonneault
`Issue Date: April 27, 2010
`Title: Extended Estrogen Dosing Contraceptive Regimen
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`Inter Partes Review No. Unassigned
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`
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`
`
`Petition for Inter Partes Review of
`U.S. Patent No. 7,704,984
`Under 35 U.S.C. §§ 311-319 and 37 C.F.R. §§ 42.1-.80, 42.100-.123
`
`
`
`Mail Stop “PATENT BOARD”
`Patent Trial and Appeal Board
`U.S. Patent and Trademark Office
`P.O. Box 1450
`Alexandria, VA 22313-1450
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`
`
`
`
`
`
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`
`
`
`
`
`MYLAN PHARMACEUTICALS INC.
`Petitioner
`v.
`WARNER-CHILCOTT COMPANY LLC.
`Patent Owner
`
`U.S. Patent No. 7,704,984 to Boissonneault
`Issue Date: April 27, 2010
`Title: Extended Estrogen Dosing Contraceptive Regimen
`
`
`
`
`
`
`
`
`
`
`
`
`Inter Partes Review No. Unassigned
`
`
`
`
`
`
`
`
`Petition for Inter Partes Review of
`U.S. Patent No. 7,704,984
`Under 35 U.S.C. §§ 311-319 and 37 C.F.R. §§ 42.1-.80, 42.100-.123
`
`
`
`Mail Stop “PATENT BOARD”
`Patent Trial and Appeal Board
`U.S. Patent and Trademark Office
`P.O. Box 1450
`Alexandria, VA 22313-1450
`
`
`
`TABLE OF CONTENTS
`
`
`Page
`
`
`TABLE OF AUTHORITIES .................................................................................. iii
`
`LIST OF EXHIBITS ................................................................................................ iv
`
`I.
`
`INTRODUCTION AND SUMMARY OF ARGUMENT ............................. 1
`
`II. MANDATORY NOTICES ............................................................................ 4
`
`A.
`
`B.
`
`C.
`
`D.
`
`Real Parties-In-Interest (37 C.F.R. § 42.8(b)(1)) ................................. 4
`
`Related Matters (37 C.F.R. § 42.8(b)(2)) ............................................. 4
`
`Identification of Counsel (37 C.F.R. § 42.8(b)(3)) .............................. 5
`
`Service Information (37 C.F.R. § 42.8(b)(4)) ...................................... 6
`
`III. GROUNDS FOR STANDING AND PROCEDURAL STATEMENT ........ 6
`
`IV. STATEMENT OF THE PRECISE RELIEF REQUESTED AND THE
`
`REASONS THEREFOR (37 C.F.R. § 42.22(A)) .......................................... 6
`
`V.
`
`THRESHOLD REQUIREMENT FOR INTER PARTES REVIEW ............ 6
`
`VI. STATEMENT FOR REASONS FOR THE RELIEF REQUESTED ............ 7
`
`A.
`
`B.
`
`C.
`
`D.
`
`Prosecution Background of the ’984 Patent ......................................... 8
`
`Level of Ordinary Skill in the Art ...................................................... 12
`
`Claim Construction ............................................................................ 13
`
`Printed Publications Relied On .......................................................... 13
`
`i
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`
`
`TABLE OF CONTENTS
`(continued)
`
`Page
`
`
`
`E.
`
`Ground 1: Claims 1-9 of the ’984 Patent Are Obvious Over the
`
`’868 Publication and the ’050 Patent and/or the ’394 Patent in
`
`further view of Sulak and the General Knowledge in the Art ........... 32
`
`F.
`
`Ground 2: Claims 1-9 of the ’984 Patent Are Obvious Over the
`
`’381 Publication and the ’050 Patent and/or the ’394 Patent in
`
`further view of the Sulak Reference and the General
`
`Knowledge in the Art ......................................................................... 47
`
`G. Ground 3: Claims 1-9 Are Obvious Over the ’490 Patent In
`
`View of the ’940 Patent and In Further View of the PDR 56 and
`
`the General Knowledge in the Art ..................................................... 53
`
`VII. CONCLUSION ............................................................................................. 60
`
`
`
`
`
`-ii-
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`TABLE OF AUTHORITIES
`
`
`CASES
`Ex parte Gelles,
`22 USPQ2d 1318 (B.P.A.I. 1992) ...................................................................... 39
`
`Page(s)
`
`In re Aller,
`220 F.2d 454 (CCPA 1955) ................................................................................ 16
`
`In re Geisler,
`116 F.3d 1465 (Fed. Cir. 1997) .......................................................................... 40
`
`In re Merck & Co., Inc.,
`800 F.2d 1091 (Fed. Cir. 1986) .......................................................................... 44
`
`In re Peterson,
`315 F.3d 1325 (Fed. Cir. 2003) .......................................................................... 16
`
`In re Wertheim,
`541 F.2d 257 (CCPA 1976) ................................................................................ 40
`
`In re Woodruff,
`919 F.2d 1575 (Fed. Cir. 1990) .......................................................................... 40
`
`Pfizer v. Apotex,
`480 F.3d 1348 (Fed. Cir. 2007) .......................................................................... 40
`
`
`
`
`
`iii
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`
`
`
`
`Ex. No.
`
`Ex. 1001
`
`Ex. 1002
`
`Ex. 1003
`
`Ex. 1004
`
`Ex. 1005
`
`Ex. 1006
`
`Ex. 1007
`
`Ex. 1008
`
`Ex. 1009
`
`LIST OF EXHIBITS
`
`
`Description
`
`U.S. Patent No. 7,704,984, titled “Extended Estrogen Dosing
`Contraceptive Regimen,” issued April 27, 2010
`
`Prosecution history of U.S. Application Ser. No. 11/112,290,
`filed April 22, 2005
`
`International Publication No. WO 97/41868, titled “Oral
`Contraceptive,” published November 13, 1997
`
`U.S. Patent No. 6,667,050, titled “Chewable Oral
`Contraceptive,” issued December 23, 2003
`
`U.S. Patent No. 5,552,394, titled “Low Dose Oral
`Contraceptives with Less Breakthrough Bleeding and
`Sustained Efficacy,” issued September 3, 1996
`
`Sulak, P. et al., “Hormone Withdrawal Symptoms in Oral
`Contraceptive Users,” Obstetrics & Gynecology, 95(2):261-
`266 (2000)
`
`United States Patent Application Publ. No. 2003/0139381,
`titled “Oral Contraceptives to Prevent Pregnancy and
`Diminish Premenstrual Symptomatology,” published July 24,
`2003
`
`U.S. Patent No. 5,756,490, titled “Pharmaceutical
`Combination Preparation for Hormonal Contraception,”
`issued May 26, 1998
`
`U.S. Patent No. 5,980,940, titled “Pharmaceutical
`Combination Preparation for Hormonal Contraception,”
`issued November 9, 1999
`
`Ex. 1010
`
`Physicians’ Desk Reference (56th ed.) (2002), 2543-2546,
`
`iv
`
`
`
`
`
`Ex. 1011
`
`Ex. 1012
`
`Ex. 1013
`
`Ex. 1014
`
`Ex. 1015
`
`Ex. 1016
`
`Ex. 1017
`
`Ex. 1018
`
`Ex. 1019
`
`2642-2650, 3423-3424
`
`Drug Details for Loestrin 21 1/20, Drugs@FDA, available at
`www.fda.gov
`
`Drug Details for Loestrin Fe 1/20, Drugs@FDA, available at
`www.fda.gov
`Clinical Gynecologic Endocrinology and Infertility, (6th ed.)
`Speroff, L. and M.A. Fritz, eds., Lippincott, Williams &
`Williams, Baltimore, MD (1999), 123-157, 201-245, 861-942
`
`Murphy, AA et al., “Effect of low-dose oral contraceptive on
`gonadotropins, androgens, a sex hormone binding globulin in
`nonhirsute women,” Fertil. Steril., 53(1):35-39 (1990)
`
`Coenen, C.M.H. et al., “Changes in androgens during
`treatment with four low-dose contraceptives,” Contraception,
`53:171-176 (1996)
`
`Guillabaud, J., “The forgotten pill - and the paramount
`importance of the pill-free week,” Brit. J. Fam. Plan.,
`12(4):35-43 (1987)
`
`Belsey, E.M., “Vaginal bleeding patterns among women
`using one natural and eight hormonal methods of
`contraception,” Contraception, 38(2):181-206 (1988)
`
`Kovacs, G., “Progestogen-only pills and bleeding
`disturbances,” Human Reprod., 11(2):20-23 (1996)
`
`Hatcher, R.A. and A. Nelson, “Combined hormonal
`contraceptive methods,” in Contraceptive Technology, (18th
`ed.), Hatcher, R.A. et al., eds., Ardent Media, Inc., New
`York, NY (2004), 391-460
`
`Ex. 1020
`
`FDA Guidance for Industry – Labeling for Combined Oral
`Contraceptives – Draft Guidance (March 2004)
`
`v
`
`
`
`
`
`Ex. 1021
`
`Ex. 1022
`
`Ex. 1023
`
`Ex. 1024
`
`Ex. 1025
`
`Ex. 1026
`
`Ex. 1027
`
`EP 206 607 A1, titled “Combination dosage form for
`premenopausal women,” published January 22, 1988
`
`Gladwell, M., “John Rock’s error what the co-inventor of the
`pill didn’t know: menstruation can endanger women’s
`health,” New Yorker, (Mar. 13, 2000)
`
`Brenner, P.F. et al., “Serum levels of d-norgestrel, luteinizing
`hormone, follicle-stimulating hormone, estradiol, and
`progesterone in women during and following ingestion of
`combined oral contraceptive containing dl-norgestrel,” Am. J.
`Obst. Gynecol. 129(2):133-140 (1977)
`
`Stubblefeld, P.G., Menstrual impact of contraception,” Am. J.
`Obstet. Gynecol. 170(5):1513-1522 (1994)
`
`Mandel, F.P. et al., “Biologic effects of various doses of
`ethinyl estradiol in postmenopausal women,” Obstet.
`Gynecol. 59(6):673-679 (1982)
`
`Mishell, D.R., Jr., “Noncontraceptive effects of oral
`contraceptives: neoplastic, reproductive, and metabolic,” in
`Management of Common Problems in Obstetrics and
`Gynecology, (3rd ed.) D.R. Mishell, Jr. and P.E. Brenner, eds.,
`Blackwell Scientific Publications, Boston, MA (1994), 805-
`818
`
`Mishell, D.R., Jr., “Contraception,” in Reproductive
`Endocrinology: Physiology, Pathophysiology, and Clinical
`Management, (4th ed.), Yen, SSC et al., eds., W.B. Saunders
`Co., Philadelphia, PA (1999), 676-708
`
`Ex. 1028
`
`Declaration of Michael A. Thomas, M.D.
`
`vi
`
`
`
`
`
`
`
`Pursuant to 35 U.S.C. §§ 311-319 and 37 C.F.R. § 42.1-.80, 42.100-.123,
`
`Mylan Pharmaceuticals Inc. (“Petitioner”) petitions for Inter Partes Review
`
`(“IPR”) of claims 1-9 of U.S. Patent No. 7,704,984, titled “Extended Estrogen
`
`Dosing Contraceptive Regimen” (“the ’984 patent,” Ex. 1001). Concurrently filed
`
`herewith are Powers of Attorney pursuant to 37 C.F.R. § 42.10(b). Pursuant to 37
`
`C.F.R. § 42.103, the fee set forth in § 42.15(a) accompanies this petition.
`
`Petitioner authorizes the Patent and Trademark Office to charge any additional fees
`
`or fee deficiencies to Deposit Acct. No. 23-1951.
`
`I.
`
`INTRODUCTION AND SUMMARY OF ARGUMENT
`
`The claims of the ’984 patent were allowed under the mistaken premise that
`
`“no art that teaches or suggests an ultra low dose of ethinyl estradiol (5-15 μg) and
`
`a placebo period of any length in a biphasic regimen lasting 28 days” could be
`
`found. (Ex. 1002, Feb. 12, 2010, Notice of Allowance) (emphasis in original).
`
`However, as set forth in this Petition, the most relevant combination of prior art
`
`known in April 2005 was not brought to the Examiner’s attention during
`
`prosecution. Most significantly, the Examiner never had the opportunity to
`
`consider the combination of (1) International Publication Number WO 97/41868
`
`(“the ’868 publication”), (2) U.S. Patent No. 6,667,050 (“the ’050 patent”), which
`
`shares a common inventor with the ’984 patent, and/or (3) U.S. Patent No.
`
`5,552,394 (“the ’394 patent”). This combination of the prior art disclosed
`
`1
`
`
`
`
`
`contraceptively effective combined oral contraceptive
`
`(“COC”)
`
`regimens
`
`incorporating daily dosages of estrogen and progestin that overlap with or fall
`
`within the scope of the claims of the ’984 patent and that were administered for the
`
`claimed 24 days of a 28-day cycle. Each of these prior art references also taught
`
`the other elements of the claims of the ’984 patent, namely, to administer either
`
`unopposed estrogen (i.e., estrogen only with no progestin) or a short placebo
`
`period (i.e., no hormones/hormone free interval) following the administration of
`
`the 24-day COC.
`
`As of 2005, the use of oral contraceptive methods to disrupt a female’s
`
`monthly reproductive cycle comprising administration of exogenous and typically
`
`synthetic hormones had been well-studied for decades. In view of this extensive
`
`knowledge, a person of ordinary skill in the art (“POSA”) in the contraceptive arts
`
`would have been motivated to combine the teachings of the prior art in this Petition
`
`to arrive with a reasonable expectation of success at a 28-day cycle of a low-dose
`
`COC regimen of ethinyl estradiol (“EE”) and norethindrone (“NE”) or
`
`norethindrone acetate (“NETA”) that contained the same benefits of prior art
`
`extended 24-day administration of COCs. Since each of the prior art references
`
`teaches using either unopposed estrogen or placebo for the remaining 4 days in the
`
`28-day cycle, in view of the known benefits of each, the POSA would have been
`
`2
`
`
`
`
`
`motivated to combine both the administration of unopposed estrogen and placebo
`
`to incorporate the known benefits during the remaining 4 days of the 28-day cycle.
`
`Specifically, in order to reduce the well-known estrogen withdrawal side
`
`effects that commonly occurred at the end of the 24-day administration of COCs,
`
`but still retain the desired artificial menstrual bleed to confirm that the female is
`
`not pregnant, the POSA would have been motivated by the knowledge in the art,
`
`including, but not limited to Sulak, P. et al., “Hormone Withdrawal Symptoms in
`
`Oral Contraceptive Users,” Obstetrics & Gynecology, 95(2):261-266 (2000)
`
`(“Sulak”), to administer both a period of unopposed estrogen and a short placebo
`
`period following administration of the 24-day COC as taught by, for example, the
`
`combination of the ’868 publication, the ’050 patent, and/or the ’394 patent. In
`
`view of the desire to further reduce estrogen withdrawal symptoms and also ensure
`
`the occurrence of the desired withdrawal bleed, the POSA would have been
`
`motivated to, and in fact, would have found it logical to, administer a 2-day
`
`unopposed estrogen period immediately following the 24-day COC administration
`
`and then administer a 2-day placebo period. Indeed, the POSA would have also
`
`arrived at the 24-2-2 regimen claimed in the ’984 patent as a matter of simple
`
`routine experimentation/optimization.
`
`The combined teachings from the prior references, as set forth in detail
`
`herein, read on the claims of the ’984 patent, which cover a method of
`
`3
`
`
`
`
`
`contraception for women comprising the sequential daily administration of three
`
`compositions over a 28-day menstrual cycle: (1) a first composition containing a
`
`progestin that is norethindrone (“NE”) or norethindrone acetate (“NETA”) in an
`
`amount equivalent to about 0.3-1.5 mg NETA and an estrogen in the amount of 5
`
`to 15 μg of EE for 24 days; (2) a second composition containing 5-15 μg of ethinyl
`
`estradiol (EE) but without any progestin for 2 days; and (3) a third composition
`
`that is a placebo (i.e., no hormones) for 2 days.
`
`Thus, this Petition demonstrates by a preponderance of the evidence that the
`
`claims of the ’984 patent are obvious at least in view of the combination of the
`
`teachings of the ’868 publication, the ’050 patent, and/or the ’394 patent in further
`
`view of Sulak and the general knowledge in the contraceptive arts. Accordingly,
`
`Petitioner requests that the claims of the ’984 patent be judged unpatentable and
`
`cancelled.
`
`II. MANDATORY NOTICES
`
`A. Real Parties-In-Interest (37 C.F.R. § 42.8(b)(1))
`
`The real parties-in-interest for this petition are Mylan Pharmaceuticals Inc.,
`
`Mylan Inc. and Famy Care Ltd.
`
`B. Related Matters (37 C.F.R. § 42.8(b)(2))
`
`On information and belief the ’984 patent has been involved in litigation
`
`styled as follows: (1) Warner Chilcott Company, LLC. v. Lupin Ltd., et al.,
`
`4
`
`
`
`
`
`C.A. No. 11-5048 (JAP) (D.N.J.); (2) Warner Chilcott Company, LLC v. Amneal
`
`Pharmaceuticals, LLC, et al., C.A. No. 12-2928 (D.N.J.); (3) Warner Chilcott
`
`Company, LLC v. Lupin Ltd. et al., C.A. No. 2014-1262, -1273 (Fed. Cir.); (4)
`
`Warner Chilcott Company, LLC. v. Mylan Inc. et al., C.A. No. 3:13-6560 (JAP)
`
`(D.N.J.); Bayer Intellectual Property GMBH et al., v. Warner Chilcott Company
`
`LLC, et al., C.A. No. 1:12-1032 (GMS) (D. Del.).
`
`C.
`
`Identification of Counsel (37 C.F.R. § 42.8(b)(3))
`
`Lead Counsel
`
`First Back-Up Counsel
`
`
`
`
`
`Cedric C.Y. Tan
`Reg. No. 56,082
`MCGUIREWOODS LLP
`
`2001 K Street N.W., Suite 400
`Washington, D.C. 20006-1040
`Telephone No.: (202) 828-2812
`Facsimile: (202) 828-2977
`Email: ctan@mcguirewoods.com
`
`
`
`Karen L. Carroll
`Reg. No. 50,748
`MCGUIREWOODS LLP
`1230 Peachtree Street, Suite 2100
`Atlanta, Georgia 30309
`Telephone No.: (404) 443-5620
`Facsimile: (404) 443-5757
`Email: kcarroll@mcguirewoods.com
`
`
`Second Back-Up Counsel
`Brie L.B. Buchanan
`Reg. No. 58,709
`MCGUIREWOODS LLP
`1230 Peachtree Street, Suite 2100
`Atlanta, Georgia 30309
`Telephone No.: (404) 443-5709
`Facsimile: (404) 443-5760
`Email: bbuchanan@mcguirewoods.com
`
`
`D.
`
`Service Information (37 C.F.R. § 42.8(b)(4))
`
`5
`
`
`
`
`
`Please direct all correspondence to lead counsel and back-up counsel at the
`
`contact information above. Petitioners consent to service by electronic mail at the
`
`email addresses set forth above.
`
`III. GROUNDS FOR STANDING AND PROCEDURAL STATEMENT
`
`Pursuant to 37 C.F.R. § 42.104(a), Petitioners certify that the ’984 patent is
`
`available for IPR and the Petitioners are not barred or estopped from requesting an
`
`IPR challenging the ’984 patent claims on the grounds identified herein and have
`
`not been party to any other post-grant review of the challenged claims.
`
`IV. STATEMENT OF THE PRECISE RELIEF REQUESTED AND THE
`REASONS THEREFOR (37 C.F.R. § 42.22(A))
`
`
`
`Petitioner requests IPR and cancellation of claims 1-9 of the ’984 patent
`
`under 35 U.S.C. § 103, as set forth herein. The ’984 patent is to be reviewed under
`
`pre-AIA § 103. Petitioners’ detailed statement of reasons for the relief requested is
`
`set forth below in the section titled “Statement of Reasons for Relief Requested.”
`
`In accordance with 37 C.F.R. § 42.6(c), copies of the exhibits are filed herewith.
`
`In addition, this Petition is accompanied by the Declaration of Michael A. Thomas,
`
`M.D., Ex. 1028.
`
`V. THRESHOLD REQUIREMENT FOR INTER PARTES REVIEW
`
`A petition for inter partes review must demonstrate “a reasonable likelihood
`
`that the petitioner would prevail with respect to at least 1 of the claims challenged
`
`in the petition.” 35 U.S.C. § 314(a). This Petition meets this threshold. As
`
`6
`
`
`
`
`
`explained below, there is a reasonable likelihood that Petitioners will prevail with
`
`respect to at least one of the challenged claims.
`
`VI. STATEMENT FOR REASONS FOR THE RELIEF REQUESTED
`
`The challenged claims of the ’984 patent are generally directed to methods
`
`of oral contraception comprising the sequential administration of a combination of
`
`progestin and estrogen (“combination oral contraceptive” or “COC”), followed by
`
`estrogen alone and placebo. The claims are invalid for as unpatentable in view of
`
`the following grounds:
`
`[Ground 1] Claims 1-9 of the ’984 patent are unpatentable as obvious under
`
`35 U.S.C. § 103 over at least (1) the ’868 publication in view of (2) the ’050 patent
`
`and/or (3) the ’394 patent in further view of (4) Sulak, P. et al., “Hormone
`
`Withdrawal Symptoms in Oral Contraceptive Users,” Obstetrics & Gynecology,
`
`95(2):261-266 (2000) (“Sulak”) and (5) the prior art evidencing the knowledge of
`
`the POSA (“General Knowledge in the Art”).
`
`[Ground 2] Claims 1-9 of the ’984 patent are unpatentable as obvious over
`
`(1) the ’381 publication, which is not cumulative of the teachings of the ’868
`
`publication, in view of (2) the ’050 patent and/or (3) the ’394 patent in further view
`
`of (4) Sulak and (5) the General Knowledge in the Art.
`
`7
`
`
`
`
`
`[Ground 3] Claims 1-9 are unpatentable as obvious over (1) the ’490 patent
`
`in view of (2) the ’940 patent and in further view of (3) PDR 56 and (4) the
`
`General Knowledge in the Art.
`
`A.
`
`Prosecution Background of the ’984 Patent
`
`During prosecution of the ’984 patent, the Applicants amended the claims to
`
`be specifically directed to methods of providing oral contraception through
`
`administration of a 24-day COC comprising a low dose of estrogen (e.g., 5-15 μg
`
`ethinyl estradiol (“EE”)) in combination with a progestin (e.g., 0.3-1.5 mg
`
`norethindrone acetate (“NETA”) or norethindrone (“NE”)), followed by 2 days of
`
`unopposed estrogen (i.e., estrogen in the absence of progestin), preferably at the
`
`same dose as the EE administered during the 24-day COC period, and finally
`
`followed by 2 days of a placebo (i.e., no hormones), for a total of 28-days of a
`
`female’s natural menstrual cycle. (Ex. 1002, Oct. 29, 2008, Preliminary
`
`Amendment).
`
`In the first Office Action on the merits, the Examiner rejected certain claims,
`
`including claim 1, as anticipated over U.S. Patent No. 5,756,490 (“the ’490
`
`patent”) under 35 U.S.C. § 102(b). (Id., Mar. 20, 2009 Office Action at 7-8).
`
`Other claims, including independent claim 28, which later issued as claim 7, were
`
`rejected as obvious under 35 U.S.C. § 103 over the ’490 patent in view of Loose-
`
`Mitchell et al., Ch. 58 Estrogens and Progestins. Goodman & Filman’s The
`
`8
`
`
`
`
`
`Pharmacological Basis of Therapeutics, 10th ed., Hardman, JG, Limbrid LE, and
`
`Gilman AG, eds., McGraw-Hill, pp. 1597-1634 (2001) (“Loose-Mitchell”) in
`
`further view of Int’l Publ. No. WO 98/04268 (“Gast”). (Id., at 8-10).
`
`In response, the Applicants amended claim 1 to reflect the species election
`
`of NETA and EE, to narrow the range of EE in both the first and second
`
`compositions to 5-15 μg, to specify that the first composition is to be administered
`
`for 24 days, and to explicitly require a third composition that is the placebo. (Id.,
`
`Jul. 13, 2009, Amendment at 2). The Applicants admitted that their amendment of
`
`claim 1 resulted in the claim requiring administration of 2 days of placebo. (Id., at
`
`5-6). Applicants also submitted the declaration of Herman Ellman, M.D. (“the
`
`Ellman Declaration”) in support of patentability. (Id., Declaration of Herman
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`Ellman Under 37 C.F.R. § 1.132). In the Ellman Declaration, the Pearl Index,
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`which measures the efficacy of a COC by calculating the number of pregnancies
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`per 100 woman-years of use, assuming thirteen 28-day cycles per year, was
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`presented for several commercially-available COCs. These included Loestrin 24, a
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`COC containing 1 mg NETA and 20 μg EE administered for 24 days followed by 4
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`days of placebo, and a COC that the Applicants contend was the commercial
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`embodiment of the ’984 patent, which contained 1 mg NETA and 10 μg EE
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`administered for 24 days, followed by 10 μg of unopposed estrogen for 2 days and
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`placebo for 2 days. (Id., at ¶7). Dr. Ellman asserted that it was unexpected that the
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`9
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`Pearl Indexes of Loestrin 24 and the alleged commercial embodiment COC both
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`fell within the acceptable range required by the FDA in light of the reduction in the
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`total amount of estrogen in the alleged commercial embodiment vis-à-vis Loestrin
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`24. (Id., at ¶8).
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`Despite dismissing the allegations in the Ellman Declaration of unexpected
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`properties, following several additional exchanges, including an in-person
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`interview, the Examiner allowed the claims, stating as his reason for allowance:
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`“[a]fter an extensive search of the art, the Examiner found no art that teaches or
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`suggests an ultra low dose of ethinyl estradiol (5-15 μg) and a placebo period of
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`any length in a biphasic regimen lasting 28 days.” (Id., Feb. 12, 2010, Notice of
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`Allowance) (emphasis in original).
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`However, the Examiner’s reason for allowance was misinformed because
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`the undisclosed prior art as of 2005, as discussed below, taught the claimed low-
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`dose COC regimens that were administered for 24 days of a 28-day cycle
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`comprising daily dosages of estrogen and progestin that overlap or fall within the
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`scope of the issued claims of the ’984 patent.1 The prior art further taught the
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`1 In re Aller, 220 F.2d 454, 456 (CCPA 1955) (“[W]here the general conditions of
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`a claim are disclosed in the prior art, it is not inventive to discover the optimum or
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`workable ranges by routine experimentation.”); see also In re Peterson, 315 F.3d
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`1325, 1330 (Fed. Cir. 2003) (“The normal desire of scientists or artisans to
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`10
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`
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`administration of unopposed estrogen or a placebo period in the remaining
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`hormone-free interval (“HFI”) of the 28-day cycle after the 24 days of COC
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`administration.
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`Moreover, the ’984 patent admitted that the following information was
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`known in the background art:
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` Contraception is controlled by progesterone and its synthetic equivalents
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`known as progestins. (Ex. 1001, 1:15-21).
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` One constant goal in the oral contraceptive art has been to reduce the
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`hormone levels of oral contraceptive compositions without reducing
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`contraceptive efficacy. (Id., 2:19-22).
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` Estrogen was provided in COCs in order to maintain good cycle control and
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`reduce irregular bleeding, such as breakthrough bleeding or spotting. (Id.,
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`1:19-21).
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` Small doses of estrogen are believed to help stabilize the endometrium and
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`allow cyclic withdrawal bleeding, similar to the natural menstrual cycle.
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`(Id., 1:21-24).
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`improve upon what is already generally known provides the motivation to
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`determine where in the disclosed percentage ranges is the optimum combination of
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`percentages.”).
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`11
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`
`
`
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` High doses of estrogen were associated with serious adverse events, such as
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`acute thrombosis. (Id., 2:22-24). Therefore, the administration of lower
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`doses of estrogen in COCs in order to reduce such adverse events was
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`desired. (Id.).
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` As estrogen doses were decreased, the incidence of unwanted breakthrough
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`bleeding or spotting increased. (Id., 2:24-26).
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`B.
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`Level of Ordinary Skill in the Art
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`A POSA is a hypothetical person presumed to be aware of all pertinent art,
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`thinks along conventional wisdom in the art, and is a person of ordinary creativity.
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`The level of skill in the contraceptive arts as of 2005, the relevant time pertaining
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`to the claimed invention of the ’984 patent, was high. A POSA in the
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`contraceptive arts in 2005 would be a person having a medical degree and at least 5
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`years of experience administering or developing oral contraceptives or,
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`alternatively, having at least an advanced degree in pharmaceuticals sciences,
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`medicinal chemistry, or a related field and at least 7-10 years of experience in the
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`design, formulation, or evaluation of oral contraceptive dosage forms. This POSA
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`would work as a part of multi-disciplinary team and can draw upon not only his or
`
`her own experience and skills, but also takes advantage of certain specialized
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`experiences and skills of others in the team, to solve a given problem.
`
`C. Claim Construction
`
`12
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`
`
`
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`In accordance with 37 C.F.R. § 42.100(b), the challenged claims must be
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`given their broadest reasonable interpretations in light of the specification of the
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`’984 patent. In the present case, Petitioner asserts that all of the terms in the
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`challenged claims should be construed according to their ordinary and customary
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`meanings.
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`D.
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`Printed Publications Relied On
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`Petitioners rely on the following patents and publications:
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`1.
`
`International Publication No. WO 97/41868 (Ex. 1003)
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`International Application PCT/US97/07074 to Michael J. Gast, entitled
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`“Oral Contraceptive” published on November 13, 1997, as International
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`Publication Number WO 97/41868 (“the ’868 publication). The ’868 publication
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`qualifies as prior art to the ’984 patent under 35 U.S.C. § 102(b) and was not cited
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`during prosecution of the ’984 patent.
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`The ’868 publication discloses a COC regimen, in which a female of child-
`
`bearing age is administered daily estrogen- and progestin-containing pills for 24
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`days and estrogen-containing only pills (i.e., unopposed estrogen) for the
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`remaining days of the 28-day cycle. (Ex. 1003, Abstract).
`
`The ’868 publication discloses
`
`that “[i]n 1978,
`
`the World Health
`
`Organization (WHO) recommended that the focus of OC research should be the
`
`development of products containing the lowest possible dose levels of estrogen and
`
`13
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`
`
`
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`progestin.”
`
`
`
`(Id., 1:22-25). Thus,
`
`the
`
`’868 publication explains
`
`that
`
`“attempts to fulfill the WHO objective” have resulted in “the dosage of EE in
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`marketed OC formulations … [being] … steadily reduced from that found in
`
`earlier OCs.” (Id., 2:9-11). In keeping with this goal, the ’868 publication teaches
`
`low dose amounts of 10-15 μg of EE for the 24-day COC period, with 15 μg of EE
`
`being preferred. (Id., 8:13-15). In each of the regimens disclosed in the two tables
`
`of the ’868 publication, the EE amount in the COC period is either 10 or 15 μg.
`
`(Id., 8:23-37; 9:7-16). For the remaining days of the 28-day cycle that contain EE
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`only (i.e., unopposed estrogen), the ’868 publication discloses a daily amount of 5-
`
`15 μg of EE with 15 μg being preferred. (Id., 8:5-7; 8:23-37; 9:7-16). The ’868
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`publication further discloses, that the amounts of EE are preferably the same in
`
`both the COC pills/tablets and the unopposed estrogen pills/tablets. (Id., 8:19-21).
`
`Thus, the teachings of the ’868 publication show that COC regimens containing
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`“an ultra low dose of ethinyl estradiol” with amounts as low as 10-15 μg EE, in
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`both a first phase (COC period) and a second phase (unopposed estrogen) were
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`known in the prior art.
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`The ’868 publication further teaches that the progestin component of the
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`COC period may be NE and NETA. (Id., 7:33-35). Although the preferred
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`progestin disclosed is levonorgestrel administered at 40-100 μg, the ’868
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`publication discloses and claims other progestins, including NE, in the regimen.
`
`14
`
`
`
`
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`(Id., 7:33-37, 12:16-18). It specifically discloses that 75 μg of levonorgestrel is
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`equivalent to 250 μg of NE, citing to EP 253 607B1 (“EP 607”), which further
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`discloses that NE and NETA are considered to be equivalent. (Id., 4:4-6; EP 607,
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`6:4-11).
`
`The ’868 publication also discloses that the COC administration should
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`begin on day 1 of the menstrual cycle and continue for 24 days of the 28-day cycle
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`and then followed by 4 days of unopposed estrogen. (Id., 8:13-15). The ’868
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`publication discloses that the advantage of administering unopposed estrogen for
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`3-5 days is “to assist in maintaining good cycle control.” (Id., 7:24-25).
`
`2.
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`U.S. Patent No. 6,667,050 (Ex. 1004)
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`U.S. Patent No. 6,667,050 (“the ’050 patent”) to Roger M. Boissonneault
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`and Tina M. deVries, entitled “Chewable Oral Contraceptive,” issued on December
`
`23, 2003, from U.S. Patent Appl. No. 09/879,028, filed on June 12, 2001. The
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`’050 patent qualifies as prior art to the ’984 patent under 35 U.S.C. § 102(b). The
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`’050 patent shares a common inventor with the ’984 patent but was not cited
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`during prosecution.
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`The ’050 patent discloses COC regimens comprising chewable, palatable
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`COC tablets. (Ex. 1004, 3:44-45). The ’050 patent discloses that the estrogen
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`component is preferably EE and the progestin component is preferably NE. (Id.,
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`4:43-46). The ’050 patent teaches that the most preferred embodiment of the
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`15
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`
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`invention contains about 10-75 μg of EE and about 0.1-2.5 mg of NE. (Id., 4:46-
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`50). In addition, the ’050 patent contains a table disclosing dose ranges, identified
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`as broad, intermediate and preferred ranges for each identified progestin and
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`estrogen agent. (Id., 4:18-35). Specifically, for the preferred estrogen, EE, the
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`’050 patent discloses dosage amounts corresponding to a broad range of 0.01-0.075
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`mg (i.e., 10-75 μg), an intermediate range of 0.015-0.05 mg (i.e., 15-50 μg), and a
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`preferred range of 0.020-0.050 mg (i.e., 20-50 μg). (Id.). The ’050 patent
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`discloses that NETA or NE may be used in dosage amounts corresponding to a
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`broad range of 0.1 to 2.5 mg, an intermediate range of 0.25-2.0 mg, and a preferred
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`range of 0.4-1.5 mg. (Id.).
`
`The ’050 patent discloses that, in the preferred method, the chewable COC
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`tablets are administered for about 21 to 25 days, followed by about 3 to 7 days of
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`placebo tablets in the 28-day cycle. (Id., 8:31-36). The teachings of the ’050
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`patent demonstrate that COC regimens containing “an ultra low dose of ethinyl
`
`estradiol” in amounts as low as from 10-15 μg of EE, followed by “a placebo
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`period … in a biphasic regimen lasting 28 days” were known in the art.
`
`3.
`
`U.S. Patent No. 5,552,394 (Ex. 1005)
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`U.S. Patent No. 5,552,394 (“the ’394 patent”) to Gary D. Hodgen, entitled
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`“Low Dose Oral Contraceptives With Less Breakthrough Bleeding and Sustained
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`Efficacy,” issued on September 3, 1996, from U.S. Pat. Appl. No. 08/279,300,
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`16
`
`
`
`
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`filed on July 22, 1994. The ’394 patent qualifies as prior art to the ’984 patent
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`under 35 U.S.C. § 102(b).
`
`The ’394 patent claims a COC regimen administered for 23-25 consecutive
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`days of a 28-day cycle, wherein the estrogen is administered in an amount
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`equivalent to about 1-35 μg of EE and the progestin is administered in an amount
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`equivalent to about 0.025-10 mg of NETA. (Ex. 1005, 8:2-12). The ’394 patent
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`further claims a COC method that comprises administering a combination of up to
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`30 μg of EE and 0.5-1.5 mg of NETA for 24 days of the 28 day cycle. (Id., 8:24-
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`37).
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`The ’394 patent also discloses that “[s]ince the advent of combined estrogen-
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`progestin medications as oral contraceptives, there has been a steady downward
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`adjustment of the daily estrogen dosage” and that “[a]ll-in-all, today’s oral
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