IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
`
`
`
`
`BEFORE THE PATENT AND TRIAL APPEAL BOARD
`
`
`
`
`
`
`INITIATIVE FOR RESPONSIBILITY IN DRUG PRICING, LLC
`Petitioner
`v.
`CELGENE CORPORATION
`Patent Owner
`
`
`
`U.S. Patent No. 6,045,501 to Elsayed et al.
`Issue Date: August 28, 1998
`Title: Methods For Delivering A Drug To A Patient While Preventing The
`Exposure Of A Foetus Or Other Contraindicated Individual To The Drug
`
`
`
`_____________________
`
`
`
`Inter Partes Review No. Unassigned
`
`_____________________
`
`
`
`Petition For Inter Partes Review Of U.S. Patent No. 6,045,501
`Under 35 Usc §§ 311-319 And 37 Cfr §42.100 Et Seq.
`
`
`
`Mail Stop "PATENT BOARD"
`Patent Trial and Appeal Board
`U.S. Patent and Trademark Office
`P.O. Box 1450
`Alexandria, VA 22313-1450
`
`
`
`Page 1 of 61
`
`CELGENE EXHIBIT 2043
`Coalition for Affordable Drugs VI LLC (Petitioner) v. Celgene Corporation (Patent Owner)
`Case IPR2015-01103
`
`

`
`
`
`TABLE OF CONTENTS
`
`I.
`
`INTRODUCTION ............................................................................................. 1
`
`II. OVERVIEW ...................................................................................................... 1
`
`III. GROUNDS FOR STANDING (37 C.F.R. § 42.104(a)); PROCEDURAL
`STATEMENTS ............................................................................................... 9
`
`IV. MANDATORY NOTICES (37 C.F.R. § 42.8(a)(1)) ...................................... 9
`
`V. STATEMENT OF THE PRECISE RELIEF REQUESTED AND THE
`REASONS THEREFOR (37 C.F.R. §42.22(a)) .........................................12
`
`VI. OVERVIEW OF U.S. PATENT NO. 6,045,501 ...........................................13
`
`VII. PROSECUTION HISTORY ........................................................................20
`
`VIII. CLAIM TERMS REQUIRING CONSTRUCTION .................................22
`
`IX. IDENTIFICATION OF THE GROUNDS FOR CHALLENGE (37 C.F.R.
`§ 42.104(b)) ....................................................................................................29
`
`A. There is a Reasonable Likelihood that at Least One Challenged Claim is
`Obvious and/or Anticipated. .......................................................................29
`
`(i) Challenge 1: Claims 1-10 ..........................................................................32
`
`(ii) Challenge 2: Claims 1-10 .........................................................................41
`
`X. CONCLUSION ................................................................................................55
`
`CERTIFICATE OF SERVICE ............................................................................56
`
`
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`
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`
`ii
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`Page 2 of 61
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`
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`Cases
`
`TABLE OF AUTHORITIES
`
`Al-Site Corp. v. VSI Int’l, Inc.,
`174 F.3d 1308 (Fed. Cir. 1999) ........................................................................................ 28
`
`Graham v. John Deere Co.,
`383 U.S. 1 (1966) ................................................................................................................... 30
`
`In re Am. Acad. of Sci. Tech. Ctr.,
`367 F.3d 1359 (Fed. Cir. 2004) ........................................................................................ 28
`
`In re GPAC Inc.,
`57 F.3d 1573 (Fed. Cir. 1995) ........................................................................................... 28
`
`KSR Int’l Co. v. Teleflex Inc.,
`550 U.S. 398 (2007) ....................................................................................................... 28, 29
`
`Multiform Desiccants, Inc. v. Medzam, Ltd.,
`133 F.3d 1473 (Fed. Cir. 1998) ........................................................................................ 21
`
`Nat’l Steel Car, Ltd. v. Canadian Pac. Ry., Ltd.,
`357 F.3d 1319 (Fed. Cir. 2004) ........................................................................................ 27
`
`Phillips v. AWH Corp.,
`415 F.3d 1303 (Fed. Cir. 2005) ........................................................................................ 21
`
`State Contracting & Eng. Corp. v. Condotte America Inc.,
`346 F.3d 1057 (Fed. Cir. 2003) ........................................................................................ 27
`
`Teleflex, Inc. v. Ficosa North America Corp,
`299 F. 3d 1313 (Fed. Cir. 2001) ....................................................................................... 22
`
`
`
`Rules
`
`37 C.F.R. § 42.10(b) ...................................................................................................................... 9
`
`37 C.F.R. § 42.104(a) .................................................................................................................... 9
`
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`iii
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`37 C.F.R. § 42.104(b) ................................................................................................................. 27
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`37 C.F.R. § 42.108(c) .................................................................................................................... 1
`
`37 C.F.R. § 42.8(a)(1) ................................................................................................................... 9
`
`37 C.F.R. § 42.8(b)(1) ................................................................................................................... 9
`
`37 C.F.R. § 42.8(b)(3) ................................................................................................................ 10
`
`37 C.F.R. § 42.8(b)(4) .............................................................................................................. 10
`
`37 C.F.R. §42.22(a) ..................................................................................................................... 11
`
`37 CFR § 42.106(a) ........................................................................................................................ 9
`
`
`
`Statutes
`
`35 U.S.C. § 102(b)................................................................................................................ 30, 39
`
`35 U.S.C. § 103(a) ....................................................................................................................... 27
`
`35 U.S.C. § 314 ............................................................................................................................... 1
`
`35 U.S.C. §§311-319 ..................................................................................................................... 1
`
`
`
`Other Authorities
`
`M.P.E.P. § 2141 ........................................................................................................................... 29
`
`M.P.E.P. §2143 ......................................................................................................................... 2, 30
`
`Office Patent Trial Practice Guide, 77 Fed. Reg. 48756 (Aug. 14, 2012) ................ 20
`
`
`
`iv
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`Page 4 of 61
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`Exhibit 1001 - U.S. Patent No. 6,045,501
`
`EXHIBITS
`
`Exhibit 1002 - Office Action, U.S. Patent Application Serial No. 09/143,569, Paper
`5, 10/07/99
`
`Exhibit 1003 - U.S. Patent Application Serial No. 09/143,569, Amendment ‘569
`Application, page 3, November 10, 1999
`
`Exhibit 1004 - Dishman et al., Pharmacists’ role in clozapine therapy at a Veterans
`Affairs medical center, Am. J. Hosp. Pharm 51: 899 (1994)
`
`Exhibit 1005 - Bastani et al., Development of the Clozaril Patient Management
`System, Psychopharmacology 99:S122 (1989)
`
`Exhibit 1006 – Powell et al., Guideline for the clinical use and dispensing of
`thalidomide, Postgrad. Med. J. 70:901 (1994)
`
`Exhibit 1007 – Declaration Matthew W. Davis M.D. RhP.
`
`Exhibit 1008 – Mitchell et al., A Pregnancy-Prevention Program in Women of
`Childbearing Age Receiving Isotrertinoin, New England J. Med.
`333(2):101 (1995)
`
`Exhibit 1009 – Honigfeld, Effects of the Clozapine National Registry System on
`Incidence of Deaths Related to Agranulocytosis, Psychiatric
`Services 47:52 (1996)
`
`Exhibit 1010 - The 47th Meeting of the Dermatologic and Ophthalmic Advisory
`Board (September 4-5, 1997, (the “FDA Meeting”)
`
`Exhibit 1011 - CDC Meeting, Centers for Disease Control, Preventing Birth
`Defects, March 26, 1997
`
`
`
`
`
`
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`v
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`I.
`
`INTRODUCTION
`
`The Initiative for Responsibility in Drug Pricing, LLC (the
`
`“Petitioner” or “IRDP”) hereby petitions for Inter Partes Review (“IPR”)
`
`(the “Petition”) under 35 U.S.C. §§311-319 seeking cancellation of claims 1-
`
`10 of U.S. Patent No. 6,045,501 (the “‘501 Patent”, Exhibit 1001). Based on
`
`the evidence presented in this Petition, the Patent Trial and Appeal Board
`
`(the “Board”) should institute an IPR because there is a reasonable
`
`likelihood that at least one of the claims challenged in the petition is
`
`unpatentable. 37 C.F.R. § 42.108(c).
`
`
`
`II. OVERVIEW
`
`In order to support a conclusion of obviousness based on the rationale
`
`of "combining prior art elements according to known methods to yield
`
`predictable results", one must articulate the following: (1) a finding that the
`
`prior art included each element claimed, although not necessarily in a single
`
`prior art reference, with the only difference between the claimed invention
`
`and the prior art being the lack of actual combination of the elements in a
`
`single prior art reference; (2) a finding that one of ordinary skill in the art
`
`could have combined the elements as claimed by known methods, and that
`
`in combination, each element merely performs the same function as it does
`
`
`
`1
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`separately; and, (3) a finding that one of ordinary skill in the art would have
`
`recognized that the results of the combination were predictable. M.P.E.P.
`
`§2143.
`
`Each and every element of the challenged claims is found in the prior
`
`art. The prior art discussed herein was not cited during prosecution of the
`
`‘501 patent. Statements made by numerous experts, including the inventors
`
`themselves, at meetings held by the Food and Drug Administration as well
`
`as the Centers for Disease Control make it clear why the prior art renders the
`
`claims obvious. Moreover, it was overwhelming clear from these meetings
`
`that everyone involved with thalidomide, from physicians, patients,
`
`regulatory agencies, pharmacies to pharmaceutical companies, was highly
`
`motivated to prevent the horrific tragedy that occurred when thalidomide
`
`was administered in the 1960s in an unregulated manner to pregnant women
`
`by putting in-place a system to tightly control distribution of the drug.
`
`A brief overview of claim 1 from the ‘501 patent, which has an
`
`effective filing date of August 28, 1998, clearly illustrates why this claim is
`
`obvious in view of the prior art. For clarity, the claim is shown in italics
`
`below.
`
`
`
`
`
`2
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`1. A method for delivering a teratogenic drug to patients in need of the drug
`
`while avoiding the delivery of said drug to a foetus comprising:
`
`Comment – Mitchell (Mitchell et al. (New England J. Med. 333(2):101
`
`(1995) (“Mitchell”)) lays-out the details of a pregnancy prevention program
`
`designed to decrease the risk of exposure of a fetus to teratogenic drugs.
`
`The program was targeted at prescribers and patients and involved
`
`guidelines for physicians, including, obtaining negative pregnancy tests, a
`
`patient-qualification checklist and providing contraceptive information. The
`
`Centers for Disease Control Meeting (CDC Meeting, Centers for Disease
`
`Control, Preventing Birth Defects, March 26, 1997 (the “CDC Meeting”))
`
`discussed the need for such programs that would include an accounting of
`
`all usage of thalidomide, an informed consent document to be signed by
`
`all subjects who receive thalidomide, distribution of an informational
`
`patient brochure and a database of all patients who take thalidomide and
`
`specifically looked to programs developed for drugs such as clozapine
`
`and isotretinoin for guidance on how to develop such a program for
`
`thalidomide.
`
`Clozapine was made available only through registered
`
`treatment centers via the Clozapine national registry. All patients must be
`
`cleared through the Clozapine national registry. Pharmacists were cleared
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`
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`3
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`via the Clozapine national registry. Based on various clinical criteria,
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`retreatment with clozapine may be denied. Dishman and Bastani disclose
`
`computerized programs for registering prescribers such as physicians,
`
`pharmacies and patients, which in the case of the Veterans Administration
`
`ties the hospital’s laboratory database to the outpatient pharmacy dispensing
`
`software and only allows clozapine prescriptions to be processed when
`
`certain clinical criteria are met (steps (a), (b) and (c) of claim 1). Dishman et
`
`al. (Am. J. Hosp. Pharm 51: 899 (1994) (“Dishman”) and Bastani et al.
`
`(Psychopharmacology 99:S122 (1989) (“Bastani”)).
`
`Powell clearly sets forth methods for delivering thalidomide to
`
`patients in need of the drug while avoiding exposure of the foetus to the
`
`drug Powell lays out explicit guidelines for identification of women of
`
`childbearing potential. Powell et al., Guideline for the clinical use and
`
`dispensing of thalidomide, Postgrad. Med. J. 70:901 (1994) (“Powell”).
`
`
`
`a. registering in a computer readable storage medium prescribers who are
`
`qualified to prescribe said drug;
`
`Comment – Honigfeld discloses the development of a clozapine national
`
`registry. (Honigfeld (Psychiatric Services 47:52 (1996) (“Honigfeld”)). The
`
`computerized database, the clozapine national registry, maintains records on
`
`
`
`4
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`physicians, pharmacies and patients. Id. “All data coming into the
`
`Clozapine national registry are entered into an integrated, computerized
`
`database maintained by the manufacturer” Id. The CDC Meeting discussed
`
`that the “FDA is also looking at various methods of helping to ensure the
`
`safe use of thalidomide by reviewing the ways other drugs with important
`
`side effects are handled” and specifically referenced a potential lethal
`
`drug, clozapine.
`
`
`
`b. registering in said medium pharmacies to fill prescriptions for said drug;
`
`Comment - The clozapine national registry provides for the responsibilities
`
`of physicians, pharmacies, patients and distributors. The computerized
`
`database, the clozapine national registry, maintains records on physicians,
`
`pharmacies and patients. Honigfeld.
`
`
`
`c. registering said patients in said medium, including information
`
`concerning the ability of female patients to become pregnant and the ability
`
`of male patients to impregnate females;
`
`Comment – Powell provides guidelines for the clinical use and dispensing
`
`of thalidomide. Before instituting therapy with thalidomide, pregnancy
`
`
`
`5
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`should be excluded by confirming a negative pregnancy test two weeks prior
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`to starting therapy.
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`d. retrieving from said medium information identifying a subpopulation of
`
`said female patients who are capable of becoming pregnant and male
`
`patients who are capable of impregnating females;
`
`Comment - Powell lays out explicit guidelines for identification of women
`
`of childbearing potential.
`
`
`
`e. providing to the subpopulation, counseling information concerning the
`
`risks attendant to fetal exposure to said drug;
`
`Comment - Powell provides specific guidelines for counseling patients
`
`concerning the risks attendant to fetal exposure to said drug and states that
`
`before treatment the patient must have a negative pregnancy test (steps (e)
`
`and (f)). Powell; see also the CDC Meeting.
`
`
`
`Dishman, Bastani and Powell all disclose the use of comprehensive
`
`counseling to the patients both before, after and during treatment (step (e)).
`
`Powell provides specific guidelines for counseling patients concerning the
`
`risks attendant to fetal exposure to said drug and states that before treatment
`
`the patient must have a negative pregnancy test (steps (e) and (f)).
`
`
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`6
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`f. determining whether patients comprising said subpopulation are
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`pregnant; and
`
`Comment - Pregnancy should be excluded before instituting therapy with
`
`thalidomide by a negative pregnancy test within 2 weeks prior to starting
`
`therapy. Mitchell et al., A Pregnancy-Prevention Program in Women of
`
`Childbearing Age Receiving Isotrertinoin, New England J. Med. 333(2):101
`
`(1995) (Mitchell). Mitchell also discusses that a negative pregnancy test
`
`should be obtained before starting therapy and delay the start of therapy until
`
`the second or third day of the next normal menstruation.
`
`
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`g. in response to a determination of non-pregnancy for said patients,
`
`authorizing said registered pharmacies to fill prescriptions from said
`
`registered prescribers for said non-pregnant registered patients.
`
`Comment - As noted above, the CDC Meeting discussed the need for such
`
`programs that would include an accounting of all usage of thalidomide, an
`
`informed consent document to be signed by all subjects who receive
`
`thalidomide, distribution of an informational patient brochure and a
`
`database of all patients who take thalidomide. Notably, the CDC
`
`Meeting looked to programs developed for drugs such as clozapine and
`
`
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`isotretinoin for guidance on how to develop such a program for
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`thalidomide.
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`Finally, with regards to step (g), “in response to a determination of
`
`non-pregnancy for said patients, authorizing said registered pharmacies to
`
`fill prescriptions from said registered prescribers for said non-pregnant
`
`registered patients”, Dishman and Bastani disclose both registered
`
`pharmacies and prescribers who require authorization in order to dispense
`
`the drug. Powell makes it clear that thalidomide should only be dispensed to
`
`a patient who is not pregnant.
`
`
`
`In summary, each and every element of claim 1 is set forth in the prior
`
`art references cited in the Petition. The Petition is accompanied by a
`
`declaration of a technical expert, Dr. Matthew W. Davis (Exhibit 1007). Dr.
`
`Davis lays out why a physician, pharmacist or medical director would have
`
`clearly combined the prior art together. Davis Declaration, Exhibit 1007.
`
`Thus, there would have been a clear motivation as well as a compelling need
`
`to create such a system given the disaster with thalidomide in the early
`
`1960s. Finally, the combination of the computerized drug monitoring and
`
`registration systems disclosed in the prior art together with the guidelines for
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`
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`8
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`dispensing thalidomide would have resulted in the establishment of a
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`completely predictable monitoring and registration system for thalidomide.
`
`The remaining dependent claims, 2-10 add nothing patentable and are
`
`discussed in greater detail below in both the Petition and Declaration.
`
`
`
`III. GROUNDS FOR STANDING (37 C.F.R. § 42.104(a));
`
`PROCEDURAL STATEMENTS
`
`Petitioner certifies that the ‘501 patent is available for IPR and that the
`
`Petitioner is not barred or estopped from requesting an IPR of any claim of
`
`the ‘501 patent on the grounds identified herein. This Petition is filed in
`
`accordance with 37 CFR § 42.106(a). Powers of Attorney are filed
`
`concurrently, as well as an Exhibit List per 37 C.F.R. § 42.10(b) and §
`
`42.63(e), respectively. The required fee is being submitted concurrently via
`
`online payment.
`
`
`IV. MANDATORY NOTICES (37 C.F.R. § 42.8(a)(1))
`
`The Real Party-In-Interest (37 C.F.R. § 42.8(b)(1)) is: Initiative
`
`for Responsibility in Drug Pricing, LLC (“Petitioner” or “IRDP”), 1020
`
`Shark Reef Road, Lopez Island Washington 98261. IRDP seeks to
`
`improve Americans’ access to low-cost generic pharmaceuticals by
`
`invalidating patents that are unjustifiably delaying generic competition.
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`IRDP is not affiliated with any pharmaceutical company, and is therefore
`
`not susceptible to the considerations that often result in settlements
`
`between brand-name and generic pharmaceutical companies that, in
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`IRDP’s view, do not serve the public interest.
`
`The Founder and President of the Initiative for Responsibility in
`
`Drug Pricing, LLC is Dr. Albert Berger. Professor Berger is the former
`
`Vice-Dean of the University of Washington Medical School and former
`
`Chair of the Department of Physiology & Graduate Education at the
`
`University of Washington. He holds grants and awards including the Ford
`
`Fellowship Foundation, Guggenheim Foundation Fellowship, Fogarty
`
`Fellowship, and two Javits Awards from the National Institutes of Health.
`
`Professor Berger holds PhDs in Chemical Engineering and Physiology
`
`from Princeton University and University of California – San Francisco.
`
`Professor Berger is the author of more than 125 medical research papers.
`
`Notice of Related Matters (37 C.F.R. § 42.8(b)(2)):
`
`Judicial matters: The ‘501 patent (Exh. 1001) is the subject of five
`
`court cases. Celgene Corporation v. Natco Pharma Limited, 2-10-cv-
`
`05197 (D.N.J.); Celgene Corporation et al. v. Barr Laboratories, Inc. et
`
`al., 2-08-cv-03357 (D.N.J.); Celgene Corporation v. Barr Laboratories,
`
`Inc. et al., 2-07-cv-05485 (D.N.J.); Celgene Corporation v. Barr
`
`10
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`Laboratories, Inc. et al., 2-07-cv-04050 (D.N.J.); Celgene Corporation v.
`
`Barr Laboratories, Inc. et al., 2-07-cv-00286 (D.N.J.). Petitioner is not a
`
`party to any of the above referenced matters.
`
`The ‘501 patent is an Orange Book listed patent for Celgene’s
`
`branded pharmaceutical drugs Thalomid and Revlimid. In Mylan
`
`Pharmaceuticals, Inc. v. Celgene Corporation, 14-cv-2094 (D.N.J.),
`
`generic drug maker Mylan alleges that Celgene unlawfully maintains
`
`monopolies over its two “lead” products—Thalomid and Revlimid—by
`
`preventing lower-priced generic competition from entering the market.
`
`Mylan alleges Celgene prevents generic manufactures from obtaining
`
`product samples for Thalomid and Revlimid, thus preventing a generic
`
`drug maker from demonstrating bioequivalence as required in an
`
`Abbreviated New Drug Application (“ANDA”). The Federal Trade
`
`Commission (“FTC”) filed an amicus brief expressing its disapproval of
`
`Celgene’s conduct. IRDP is not a party to this matter.
`
`Administrative matters: (1) In Petitions filed concurrently herewith,
`
`Petitioner seeks IPR of U.S. Pat. No. 6,315,720, which is against the same
`
`Patent Owner.
`
`Designation of Lead and Back-Up Counsel (37 C.F.R. § 42.8(b)(3)):
`
`Lead Counsel
`
`Back-Up Counsel
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`11
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`Tarek N. Fahmi
`USPTO Reg. No. 41,402
`
` D
`
` +1 408 799 0612
`T +1 866 877 4883
`F +1 408 773 6177
`
`tarek.fahmi@ascendalaw.com
`
`Ascenda Law Group, PC
`84 W. Santa Clara St.
`Suite 550
`San Jose, CA 95113-1812
`
`Michael A. Davitz M.D. J.D.
`USPTO Reg. No. 47,519
`
`D: +1 914-582-8817
`T: +1 866-877-4883
`F: +1 408-773-6177
`
`michael.davitz@ascendalaw.com
`
`Ascenda Law Group, PC
`84 W. Santa Clara St.,
`Suite 550

`San Jose, CA 95113-1812
`
`
`
`Notice of Service Information (37 C.F.R. § 42.8(b)(4)): Please
`
`
`
`
`
`
`
`direct all correspondence to lead counsel at the above address. Petitioners
`
`
`consent to email service at: michael.davitz@ascendalaw.com and
`
`tarek.fahmi@ascendalaw.com.
`
`V.
`
`STATEMENT OF THE PRECISE RELIEF REQUESTED AND
`
`THE REASONS THEREFOR (37 C.F.R. §42.22(a))
`
`
`
`Petitioners request IPR and cancellation of claims 1-10 of the ‘501
`
`patent. A summary of the reasons for the relief is set forth in §II and in
`
`greater detail below.
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`
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`VI. OVERVIEW OF U.S. PATENT NO. 6,045,501
`
`
`
`The ‘501 patent issued on April 4, 2000 and has an effective filing
`
`date of August 28, 1998. The patent describes methods for delivering a drug
`
`to a patient, while preventing the exposure of the fetus or other
`
`contraindicated individuals to the drug. In various embodiments,
`
`prescribers, pharmacies, and patients are registered in a computer database.
`
`The registered patients receive counseling regarding the risks related to fetal
`
`exposure to the drug. Under certain circumstances male patients and female
`
`patients who are not pregnant, can receive the drug. Exhibit 1001 at
`
`Abstract.
`
`There are 10 claims with a single independent claim which is
`
`reproduced below.
`
`1. A method for delivering a teratogenic drug to patients in need of the
`
`drug while avoiding the delivery of said drug to a foetus comprising:
`
`a. registering in a computer readable storage medium prescribers who
`
`are qualified to prescribe said drug;
`
`b. registering in said medium pharmacies to fill prescriptions for said
`
`drug;
`
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`c. registering said patients in said medium, including information
`
`concerning the ability of female patients to become pregnant and the
`
`ability of male patients to impregnate females;
`
`d. retrieving from said medium information identifying a
`
`subpopulation of said female patients who are capable of becoming
`
`pregnant and male patients who are capable of impregnating females;
`
`e. providing to the subpopulation, counseling information concerning
`
`the risks attendant to fetal exposure to said drug;
`
`f. determining whether patients comprising said subpopulation are
`
`pregnant; and
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`g. in response to a determination of non-pregnancy for said patients,
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`authorizing said registered pharmacies to fill prescriptions from said
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`registered prescribers for said non-pregnant registered patients.
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`The dependent claims, claims 2-10, recite the following limitations:
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`(i) claim 2, the method of claim 1 wherein said drug is thalidomide; (ii)
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`claim 3, the method of claim 1 further comprising including in said
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`registering information concerning male patients who are capable of
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`impregnating females and including said males within said subpopulation;
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`(iii) claim 4, the method of claim 1 wherein said determination comprises
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`pregnancy testing; (iv) claim 5, the method of claim 1 wherein the issuance
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`and fulfillment of said prescriptions are recorded in said computer readable
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`storage medium; (v) claim 6, the method of claim 1 wherein refilling of said
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`prescriptions is authorizable only in response to information contained on
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`said computer readable storage medium; (vi) claim 7, the method of claim 1
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`wherein said prescriptions are filled for no more than about 28 days; (vii)
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`claim 8, the method of claim 1 wherein said prescriptions are filled together
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`with distribution of literature warning of the effects of said drug upon
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`fetuses; (viii) claim 9, the method of claim 1 further comprising providing
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`said patients with contraception counseling; and, (ix) claim 10, the method
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`of claim 1 further comprising: h. providing to said patients who are capable
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`of becoming pregnant a contraceptive device or formulation.
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`The drug delivery methods described involve first registering
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`prescribers, who are qualified to prescribe a teratogenic drug, in a computer
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`readable storage medium. Exhibit 1001 at 4:10-15. Prescribers are “any
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`individual who are capable of prescribing drugs, including, for example,
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`medical doctors.” Id. at 3:30-33. In order to become registered, the
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`prescriber may be required to provide patient counseling and education. Id.
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`at 4:19-21. Registration can be achieved by mail, facsimile or on-line
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`transmission and the prescriber may be asked to provide certain information
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`as part of the registration, including, name, address and health care
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`institution affiliation. Id. at 4:35-40. A pharmacy that can fill the
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`prescription for the drug can become registered in a computer readable
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`medium in a similar manner. Id. at 5:1-23.
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`The patient must also be registered in a computer readable medium.
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`In order to be registered in the computer readable medium, the patient needs
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`to comply with various requirements. For example, the patient needs to
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`supply her/his name, mailing address and date of birth. Id. at 5:43-45. In
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`addition, other information is also entered into the computer readable storage
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`medium allowing the prescriber or distributor of the drug to “glean
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`therefrom information regarding the level of risk associated with the
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`administration of the involved drug to various patient.” Id. at 8:28-32.
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`The types of information can include a patient survey conducted
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`before, during and after treatment with the drug. Id. at 8:10-12. “The
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`patient survey provides information, for example, to the prescriber,
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`manufacturer and/or distributor of the drug, as well as to any group or body
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`which may be established to generally provide oversight on the distribution
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`of the drug, on information regarding the general lifestyle of the patient,
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`including detailed information on the patient's sexual behavior.” Id. at 8:15-
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`20. The patient may also be required to receive counseling on birth control
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`and fill-out an informed consent. Id. at 7:33-38.
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`The information can then be used to identify various subpopulations.
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`Specifically, “[o]nce entered into the computer readable storage medium, the
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`prescriber, manufacturer and/or distributor of the drug may be able to glean
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`therefrom information regarding the level of risk associated with the
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`administration of the involved drug to the various patients. Accordingly, it
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`may be possible to identify, from among the entire population of registered
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`patients, one or more subpopulations of patients for which the involved drug
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`may be more likely to be contraindicated. For example, it may be possible
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`to identify a subpopulation of female patients who are capable of becoming
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`pregnant and/or a subpopulation of male patients who are capable of
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`impregnating female patients. Preferably, the counseling information
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`discussed above relating to exposure of a foetus to a teratogenic drug may
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`then be addressed primarily to this subpopulation of patients.” Id. at 8:28-
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`42.
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`Counseling is provided to both male and female patients. Extensive
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`details on the nature of the counseling are set forth in the specification. The
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`counseling may be provided verbally, in written form or through
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`instructional videos. Id. at 6:15-20. Excerpts from the patent are provided
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`below.
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`Female Patients - “[T]he prescriber preferably counsels female patients that
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`such drugs must never be used by pregnant women. If the patient is a female
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`of child-bearing potential (i.e., a woman who is capable of becoming
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`pregnant), the prescriber preferably counsels the patient that even a single
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`dosage of certain teratogenic drugs, such as thalidomide, may cause birth
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`defects. Accordingly, the patient is preferably counseled to avoid sexual
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`intercourse entirely, or if sexually active, to use appropriate forms of
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`contraception or birth control. For both male and female patients, the
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`prescriber preferably provides counsel on the importance of using at least
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`two forms of effective birth control methods, with one form preferably being
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`a highly effective hormonal method, and the other form preferably being an
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`effective barrier method. The patients are preferably counseled to use the
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`birth control methods for a period of time prior to and during treatment with
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`the teratogenic drug, as well as for a period of time after treatment with the
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`drug has been terminated.” Id. at 6:27-46.
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`Male Patients - “Male patients who are being prescribed a teratogenic drug
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`are preferably counseled to use condoms every time they engage in sexual
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`relations, since many teratogenic drugs may be found in semen. Male
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`patients are also preferably counseled to contact their prescriber if they have
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`sexual intercourse without a condom, and/or if it is believed that they may
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`have caused a pregnancy.” Id. at 6:54-60.
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`Prescriber – The prescriber may also “advise the patient to not share the drug
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`with anyone else, and particularly that the drug should be kept out of the reach
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`of children as well as women of child-bearing potential. In the case of female
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`patients, particularly female patients of child-bearing potential, the prescriber
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`should give the patient a pregnancy test, preferably a serum pregnancy test,
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`prior to and during treatment with the teratogenic drug. To begin receiving the
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`teratogenic drug and to continue taking the drug, female patients of child-
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`bearing potential should continue to have negative pregnancy tests.” Id. at
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`7:12-24.
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`Before filling and dispensin