Ipr2015 01103

Paper No.
______
Filed: April 23, 2015
UNITED STATES PATENT AND TRADEMARK OFFICE
____________________
BEFORE THE PATENT TRIAL AND APPEAL BOARD
___________________
COALITION FOR AFFORDABLE DRUGS VI LLC
PETITIONER
V.
CELGENE CORPORATION
PATENT OWNER
___________________
CASE NO.: UNASSIGNED
PATENT NO. 6,315,720
FILED: OCTOBER 23, 2000
ISSUED: NOVEMBER 13, 2001
INVENTORS: BRUCE A. WILLIAMS, JOSEPH K. KAMINSKI
TITLE: METHODS FOR DELIVERING A DRUG TO A PATIENT WHILE
AVOIDING THE OCCURRENCE OF AN ADVERSE SIDE EFFECT KNOWN
OR SUSPECTED OF BEING CAUSED BY THE DRUG
___________________
PETITION FOR INTER PARTES REVIEW
OF U.S. PATENT NO. 6,315,720
Patent No. 6,315,720

TABLE OF CONTENTS
I.
INTRODUCTION................................................................................................... 1
II.
GROUNDS FOR STANDING (37 C.F.R. 42.104(a)) ..................................... 1
III.
MANDATORY NOTICES (37 C.F.R. 42.8)..................................................... 1
A. Real Parties-in-Interest (37 C.F.R. 42.8(b)(1)) .................................................... 1

B.
Related Judicial and Administrative Matters (37 C.F.R. 42.8(b)(2)) ................. 2
C.
Lead and Back-Up Counsel (37 C.F.R. 42.8(b)(3)) and Service

Information (37 C.F.R. 42.8(b)(4)) ....................................................................... 3
IV.
PAYMENT OF FEES (37 C.F.R. 42.15(a) and 42.103) ................................ 3
V.
IDENTIFICATION OF CHALLENGE ............................................................. 3

A. Overview of U.S. Patent No. 6,315,720 ................................................................. 3
1.
The 720 Patent Specification ............................................................................. 4
2.
The 720 Claims .................................................................................................... 5
3.
The 720 Prosecution History ............................................................................. 6
B.
Claim Construction of Challenged Claims ............................................................. 9

1.
Consulted ......................................................................................................... 10
2.
Teratogenic effect ........................................................................................... 10
3.
Adverse side effect ......................................................................................... 11
C.
Statement of Precise Relief Requested for Each Claim Challenged ................. 11

1.
Claims for Which Review is Requested ........................................................... 11
2.
Statutory Grounds of Challenge ....................................................................... 11
D. Overview of the State of the Art and Motivation to Combine ......................... 11

1.
E.
VI.
Summary of the Petitions Prior Art References ............................................ 14

Level of Ordinary Skill in the Art .......................................................................... 17
DETAILED EXPLANATION OF THE CHALLENGE .............................. 17
A. Ground 1: Claims 132 of U.S. Patent No. 6,315,720 are

obvious under 35 U.S.C. 103(a) over Mitchell in view of
i

Dishman and in further view of Cunningham and the knowledge
of one of ordinary skill in the art. .......................................................................... 17
VII.
1.
Claim 1 is obvious over Mitchell in view of Dishman and in

further view of Cunningham. .............................................................................. 17
2.
Dependent Claims 26 are obvious over the prior art of

Ground 1, and more specifically over Mitchell in view of
Dishman and in further view of the knowledge of one of
ordinary skill in the art. ..................................................................................... 25
3.

4.
Dependent Claims 1114 and 2025 are obvious over the

prior art of Ground 1, and more specifically over Mitchell in
view of the knowledge of one of ordinary skill in the art. ............................ 31
5.
Dependent Claim 15 is obvious over the prior art of Ground 1,

and more specifically over Mitchell in view of Dishman and in
further view of the knowledge of one of ordinary skill in the art................ 35
6.

7.
Dependent Claims 1819 and 2627 are obvious over the

prior art of Ground 1, and more specifically over Mitchell in
view of Dishman and in further view of the knowledge of one
of ordinary skill in the art.................................................................................. 38
8.
The added limitations of independent Claim 28 and dependent

Claims 2932 are obvious over Mitchell in view of Dishman and
in further view of Cunningham and knowledge of one of ordinary
skill in the art. ..................................................................................................... 41
9.
Claim chart for Ground 1 showing exemplary citations in

Mitchell, Dishman, and Cunningham. ................................................................... 46
CONCLUSION ...................................................................................................... 60
ii

TABLE OF AUTHORITIES
Cases
Abbott Labs v. Andrx Pharms., Inc.,
452 F.3d 1331 (Fed. Cir. 2006) ....................................................................................... 24
Bayer Schering Pharma AG v. Barr Labs., Inc.,
575 F.3d 1341 (Fed. Cir. 2009) ....................................................................................... 23
Dow Chem. Co. v. Sumitomo Chem. Co.,
257 F.3d 1364 (Fed. Cir. 2001) ....................................................................................... 18
Dystar Textilfarben GmbH v. C.H. Patrick Co.,
464 F.3d 1356 (Fed. Cir. 2006) ....................................................................................... 25
In re Glatt Air Techniques, Inc.,
630 F.3d 1026 (Fed. Cir. 2011) ....................................................................................... 18
In re Icon Health & Fitness, Inc.,
496 F.3d 1374 (Fed. Cir. 2007) ....................................................................................... 19
In re Kahn,
441 F.3d 977 (Fed. Cir. 2006) ......................................................................................... 43
In re Venner,
262 F.2d 91 (C.C.P.A. 1958) ........................................................................................... 38
KSR Intl Co. v. Teleflex Inc.,
550 U.S. 398 (2007)....................................................................................... 23, 24, 40, 41
Pacing Techs., LLC v. Garmin Intl, Inc.,
778 F.3d 1021 (Fed. Cir. 2015) ....................................................................................... 10
Par Pharm., Inc. v. TWi Pharms., Inc.,
773 F.3d 1186 (Fed. Cir. 2014) ...........................................................................20, 22, 44
Pentec, Inc. v. Graphic Controls Corp.,
776 F.2d 309 (Fed. Cir. 1985) ...................................................................... 18, 28, 33, 42
Pfizer, Inc. v. Apotex, Inc.,
480 F.3d 1348 (Fed. Cir. 2007) ....................................................................................... 21
Rogers v. Desa Intl, Inc.,
198 Fed. Appx. 918 (Fed. Cir. 2006) ............................................................................. 21
Sciele Pharma, Inc. v. Lupin Ltd.,
684 F.3d 1253 (Fed. Cir. 2012) ................................................................................. 34, 45
Tyco Healthcare Grp. LP v. Ethicon Endo-Surgery, Inc.,
774 F.3d 968 (Fed. Cir. 2014) ................................................................................... 21, 30
iii

Unigene Labs., Inc. v. Apotex, Inc.,
655 F.3d 1352 (Fed. Cir. 2011) ....................................................................................... 31
Rules
37 C.F.R. 42.103 .................................................................................................................. 3
37 C.F.R. 42.15(a) ................................................................................................................ 3
37 C.F.R. 42.8(b)(1) ............................................................................................................. 1
iv

TABLE OF EXHIBITS
Exhibit No.
Description
Exhibit 1001
U.S. Patent No. 6,315,720 to Bruce A. Williams and Joseph K.

Kaminski, filed on Oct. 23, 2003, and issued on Nov. 13, 2001 (the
720 Patent)
Exhibit 1002
U.S. Patent No. 6,315,720 Prosecution History (720 prosecution

history)
Exhibit 1003
U.S. Patent No. 6,045,501 to Marc Elsayed and Bruce Williams, filed
on Aug. 28, 1998, and issued on Apr. 4, 2000 (Elsayed)
Exhibit 1004
U.S. Patent No. 6,063,026 to Mark A. Schauss and Patricia Kane,

filed on Mar. 22, 1996, and issued on May 16, 2000 (Schauss)
Exhibit 1005
U.S. Patent No. 6,202,923 to Joseph H. Boyer et al., filed on Aug. 23,
1999, and issued on Mar. 20, 2001 (Boyer)
Exhibit 1006
Guideline for the clinical use and dispensing of thalidomide, R.J.

Powell and J.M.M Gardner-Medwin, Postgrad Med. J. (1994) 79,
901904 (Powell)
Exhibit 1007
Pharmacists role in clozapine therapy at a Veterans Affairs medical

center, Benjamin R. Dishman et al., Am. J. Hosp. Pharm. (Apr. 1,
1994) 51, 899901 (Dishman)
Exhibit 1008
U.S. Patent No. 5,832,449 to David W. Cunningham, filed on Nov.

13, 1995, and issued on Nov. 3, 1998 (Cunningham)
Exhibit 1009
U.S. Patent No. 6,055,507 to David W. Cunningham, filed on Aug.

20, 1998, and issued on Apr. 25, 2000 (Cunningham Divisonal)
Exhibit 1010
A Pregnancy-Prevention Program in Women of Childbearing Age

Receiving Isotretinoin, Allen A. Mitchell et al., New Eng. J. Med.
(Jul. 13, 1995) 333:2, 10106 (Mitchell)
Exhibit 1011
S.T.E.P.S.TM: A Comprehensive Program for Controlling and

Monitoring Access to Thalidomide, Jerome B. Zeldis et al., Clinical
Therapeutics (1999) 21:2, 31930 (Zeldis)
Exhibit 1012
Transcript of the FDAs Forty-Seventh Meeting of the

Dermatologic and Ophthalmic Drugs Advisory Committee, Sept. 4,
1997 (FDA Meeting Part 1)

Exhibit No.
Description
Exhibit 1013
Transcript of the FDAs Forty-Seventh Meeting of the

Dermatologic and Ophthalmic Drugs Advisory Committee, Sept. 5,
1997 (FDA Meeting Part 2)
Exhibit 1014
CDC Meeting: 03/26/1997 Minutes and Agenda Regarding

Thalidomide (CDC Meeting)
Exhibit 1015
Assessing the Effectiveness of a Computerized Pharmacy System,

Reed M. Gardner et al., Decision Support Systems in Critical Care,
1994, M.M. Schabot et al., eds. (Gardner)
Exhibit 1016
Review of computer applications in institutional pharmacy1975

1981, Ken W. Burleson, Am. J. Hosp. Pharm. (1982) 39:5370
(Burleson)
Exhibit 1017
Interactive Voice Response Systems in Clinical Research and

Treatment, James C. Mundt, Psychiatric Services (May 1997) 48:5,
61112, 623 (Mundt)
Exhibit 1018
Passage of Chemicals into Human and Animal Semen: Mechanisms

and Significance, Thaddeus Mann and Cecelia Lutwak-Mann, CRC
Critical Reviews in Toxicology (1982) 11:1, 114 (Mann)
Exhibit 1019
Preparing for Thalidomides Comeback, Cori Vanchieri, Annals of

Internal Med. (Nov. 15 1997) 127:10, 95154 (Vanchieri)
Exhibit 1020
Development of a Computerized Drug Interaction Database

(MedicomSM) for Use in a Patient Specific Environment, Arthur F.
Shinn et al., Drug Inform. J. (1983) 17:20510 (Shinn)
Exhibit 1021
Decision support for drug prescription integrated with computerbased patient records in primary care, R. Linnarsson, Med. Inform.
18:2, 13142 (Linnarsson)
Exhibit 1022
A medication database a tool for detecting drug interactions in

hospital, P.E. Grnroos et al., Eur. J. Clin. Pharmacol. (1997) 53:13
17 (Grnroos)
Exhibit 1023
Prevalence of Alcohol and Drug Abuse in Schizophrenic

Inpatients, M. Soyka et al., Eur. Arch. Psychiatry Clin. Nerosci.
(1993) 242:36272 (Soyka)
Exhibit 1024
Alcohol, Cannabis, Nicotine, and Caffeine Use and Symptom

Distress in Schizophrenia, Edna Hamera et al., J. of Nervous and
Mental Disease (Sept. 1995) 183:9, 55965 (Hamera)
vi

Exhibit No.
Description
Exhibit 1025
Substance Abuse and Schizophrenia: Editors Introduction,

Thomas R. Kosten and Douglas M. Ziedonis, Schizophrenia Bulletin
(1997) 23:2, 18186 (Kosten)
Exhibit 1026
Substance Abuse and Women on Welfare, Jeffrey C. Menill,

National Center on Addiction and Substance Abuse at Columbia
University, June 1994 (Menill)
Exhibit 1027
Declaration of Jeffrey Fudin, R.Ph., B.S., Pharm.D., DAAPM, FCCP,

FASHP (Fudin Decl.)
Exhibit 1028
Curriculum Vitae for Jeffrey Fudin, R.Ph., B.S., Pharm.D., DAAPM,

FCCP, FASHP (Fudin CV)
Exhibit 1029
Center for Drug Evaluation and Research Approval Package for

Application Number: 18-662/S-038 (Accutane Label)
Exhibit 1030
Joint Claim Construction and Prehearing Statement, Celgene Corp. v.

Natco Pharma Ltd., NJD-2-10-cv-05197, Jul. 18, 2011 (Celgene Claim
Construction Brief)
Exhibit 1031
Center for Drug Evaluation and Research Approval Package for:

Application Number NDA 20-785 Approval Letter(s), Sept. 19,
1997, and Jul. 16, 1998 (FDA Thalomid Approval Letters)
Exhibit 1032
Influence of Socially Desirable Responding in a Study of Stress and

Substance Abuse, John W. Welte and Marcia Russell, Alcohol. Clin.
Exp. Res. (Jul./Aug. 1993) 17:4, 75861 (Welte)
Exhibit 1033
Thalidomide BackUnder Strict Control, JAMA: Medical News and

Perspectives (Oct. 8, 1997) 278:14, 113537 (JAMA)
vii

I.
INTRODUCTION
Petitioner Coalition For Affordable Drugs VI LLC (CFAD), requests an Inter
Partes Review (IPR) of Claims 132 (collectively, the Challenged Claims) of U.S.
Patent No. 6,315,720 (the 720 Patent) (Ex. 1001) in accordance with 35 U.S.C.
31119 and 37 C.F.R. 42.100 et seq.
II.
GROUNDS FOR STANDING (37 C.F.R. 42.104(A))

Pursuant to 37 C.F.R. 42.104(a), Petitioner certifies that the 720 Patent is
available for IPR and that Petitioner is not barred or estopped from requesting IPR
challenging the Claims of the 720 Patent on the grounds identified in this Petition.
III.
A.
MANDATORY NOTICES (37 C.F.R. 42.8)

Real Parties-in-Interest (37 C.F.R. 42.8(b)(1))
Pursuant to 37 C.F.R. 42.8(b)(1), Petitioner certifies that Coalition For
Affordable Drugs VI LLC (CFAD VI), Hayman Credes Master Fund, L.P.
(Credes), Hayman Orange Fund SPC Portfolio A (HOF), Hayman Capital
Master Fund, L.P. (HCMF), Hayman Capital Management, L.P. (HCM), Hayman
Offshore Management, Inc. (HOM), Hayman Investments, L.L.C. (HI), nXn
Partners, LLC (nXnP), IP Navigation Group, LLC (IPNav), J. Kyle Bass, and
Erich Spangenberg are the real parties in interest (collectively, RPI). The RPI
hereby certify the following information: CFAD VI is a wholly owned subsidiary of
Credes. Credes is a limited partnership. HOF is a segregated portfolio company.
HCMF is a limited partnership. HCM is the general partner and investment manager
1

of Credes and HCMF. HCM is the investment manager of HOF. HOM is the
administrative general partner of Credes and HCMF. HI is the general partner of
HCM. J. Kyle Bass is the sole member of HI and sole shareholder of HOM. CFAD
VI, Credes, HOF and HCMF act, directly or indirectly, through HCM as the general
partner and/or investment manager of Credes, HOF and HCMF. nXnP is a paid
consultant to HCM. Erich Spangenberg is the 98.5% member of nXnP. IPNav is a
paid consultant to nXnP. Erich Spangenberg is the 98.5% member of IPNav. Other
than HCM and J. Kyle Bass in his capacity as the Chief Investment Officer of HCM
and nXnP and Erich Spangenberg in his capacity as the Manager/CEO of nXnP, no
other person (including any investor, limited partner, or member or any other person
in any of CFAD VI, Credes, HOF, HCMF, HCM, HOM, HI, nXnP or IPNav) has
authority to direct or control (i) the timing of, filing of, content of, or any decisions or
other activities relating to this Petition or (ii) any timing, future filings, content of, or
any decisions or other activities relating to the future proceedings related to this
Petition. All of the costs associated with this Petition will be borne by HCM, CFAD
VI, Credes, HOF and/or HCMF.
B.
Related Judicial and Administrative Matters (37 C.F.R. 42.8(b)(2))

Pursuant to 37 C.F.R. 42.8(b)(2), Petitioner states that the 720 Patent has
been the subject of the following lawsuits: Celgene Corp. et al. v. Lannett Holdings, Inc. et
al., NJD-2-15-00697 (filed Jan. 30, 2015); Celgene Corp. v. Natco Pharma Ltd., NJD-2-10cv-05197 (filed Oct. 8, 2010); Celgene Corp. et al. v. Barr Laboratories, Inc. et al., NJD-22

08-cv-03357 (filed July 3, 2008); Celgene Corp. et al. v. Barr Laboratories, Inc. et al., NJD-207-cv-05485 (filed Nov. 14, 2007); Celgene Corp. et al. v. Barr Laboratories, Inc. et al., NJD2-07-cv-04050 (filed Aug. 23, 2007); Celgene Corp. et al. v. Barr Laboratories, Inc. et al.,
NJD-2-07-cv-00286 (filed Jan. 18, 2007).
C.
Lead and Back-Up Counsel (37 C.F.R. 42.8(b)(3)) and Service

Information (37 C.F.R. 42.8(b)(4))
Lead counsel is Sarah E. Spires, Reg. No. 61,501,
sarah.spires@skiermontpuckett.com. Back-up counsel are Ki O, Reg. No. 68,952,

ki.o@skiermontpuckett.com; Dr. Parvathi Kota, Reg. No. 65,122,
parvathi.kota@skiermontpuckett.com; and Paul J. Skiermont (pro hac vice requested),
paul.skiermont@skiermontpuckett.comall of Skiermont Puckett LLP, 2200 Ross
Ave. Ste. 4800W, Dallas, Texas 75201, P: 214-978-6600/F: 214-978-6601. Petitioner
consents to electronic service.
IV.
PAYMENT OF FEES (37 C.F.R. 42.15(a) and 42.103)

The required fees are submitted herewith in accordance with 37 C.F.R.
42.103(a) and 42.15(a). If any additional fees are due during this proceeding, the
Office is authorized to charge such fees to Deposit Account No. 506293. Any
overpayment or refund of fees may also be deposited in this Deposit Account.
V.
IDENTIFICATION OF CHALLENGE
A.
Overview of U.S. Patent No. 6,315,720

The 720 Patent is titled Methods for Delivering a Drug To A Patient While
Avoiding The Occurrence Of An Adverse Side Effect Known Or Suspected Of Being

3

Caused By The Drug. (Ex. 1001 at Front Cover.) The underlying application, U.S.
Patent Application Serial No. 09/694,217, was filed on October 23, 2000. The 720
Patent issued to Bruce Williams and Joseph K. Kaminski on November 13, 2001. (Id.)
1.
The 720 Patent Specification
The 720 Patent claims methods for delivering a drug to a patient, while
avoiding the occurrence of adverse side effects. (Ex. 1001 at Abstract.) The 720
Patent generally describes methods for the distribution to patients of drugs,
particularly teratogenic drugs, in ways wherein such distribution can be carefully
monitored and controlled. (Id. at 1:1316.) A teratogenic drug can cause severe birth
defects when administered to a pregnant woman. (Id. at 1:2729.) The 720
specification acknowledges that prior [m]ethods for monitoring and educating
patients to whom a drug is distributed have been developed in connection with a
known teratogenic drug (isotretinoin), including a pregnancy prevention program.
(Id. at 2:1320.)
The invention of the 720 Patent was allegedly conceived in the context of the
FDA approval of thalidomidea teratogenic drug effective in treating a variety of
diseaseswhen the inventors were seeking methods to control the distribution of
[thalidomide] so as to preclude administration to fetuses. (Id. at 1:4664.)
The 720 Patents invention can be summarized as: (1) filling prescriptions only
after consulting a computer readable storage medium to confirm that the prescribers,
pharmacies, and patients are registered in a computer database; (2) assigning patients
4

to risk groups based on the risk that the drug will cause adverse side effects and
entering the risk group assignment in the storage medium; (3) determining the
acceptability of the likely adverse effect; and (4) generating a prescription approval
code to said pharmacy before said prescription is filled. (Id. at 2:493:4.) The 720
Patent specification also teaches that [t]he invention is not limited to the distribution
of teratogenic drugs; other potentially hazardous drugs may also be distributed in
accordance with embodiments of this invention in such a fashion that persons for
whom such drugs are contraindicated will not receive them. (Id. at 3:2126.)
The patent also discloses that when a patient is registered in the computer
readable storage medium, information probative of the risk of a drugs side effects is
also collected from the patient. (Id. at 6:3033.) This information can then be
compared with a defined set of risk parameters for the drug, allowing for assignment
of the patient to a particular risk group. (Id. at 6:3336.) If the risk of adverse side
effects is deemed acceptable, the patient may receive the drug from a registered
pharmacy, subject to conditions such as a negative pregnancy test, but may not receive
refills without a renewal prescription from the prescriber. (Id. at 11:6212:8.)
2.
The 720 Claims
The 720 Patent has two independent claims and 30 dependent claims. Claim 1
is representative and is reproduced below.
In a method for delivering a drug to a patient in need of the drug, while
avoiding the occurrence of an adverse side effect known or suspected of
5

being caused by said drug, wherein said method is of the type in which
prescriptions for said drug are filled only after a computer readable
storage medium has been consulted to assure that the prescriber is
registered in said medium and qualified to prescribe said drug, that the
pharmacy is registered in said medium and qualified to fill the
prescription for said drug, and the patient is registered in said medium
and approved to receive said drug, the improvement comprising:
a. defining a plurality of patient risk groups based upon a
predefined set of risk parameters for said drug;
b. defining a set of information to be obtained from said patient,
which information is probative of the risk that said adverse side effect is
likely to occur if said drug is taken by said patient;
c. in response to said information set, assigning said patient to at
least one of said risk groups and entering said risk group assignment in
said medium;
d. based upon said information and said risk group assignment,
determining whether the risk that said adverse side effect is likely to
occur is acceptable; and
e. upon a determination that said risk is acceptable, generating a
prescription approval code to be retrieved by said pharmacy before said
prescription is filled.
(Id. at 18:1742.) All other claim limitations are listed within Ground 1 below.
3.
The 720 Prosecution History
During prosecution of U.S. Patent Application No. 09/694,217 (filed October

23, 2000), which led to the 720 Patent, the Examiner initially rejected Claims 127 as
obvious under 35 U.S.C. 103(a) over U.S. Patent No. 6,045,501 (Ex. 1003, Elsayed)
6

in view of U.S. Patent No. 6,063,026 (Ex. 1004, Schauss). (See Ex. 1002 at 5758.1)
At this time, Claims 132 were pending. (Id. at 56.) Claim 1, the only independent
claim, recited a method for delivering a drug to a patient in need of the drug while
avoiding the occurrence of an adverse side effect known or suspected of being caused
by said drug. (Id. at 44.)
The Examiner rejected Claims 127, stating that Elsayed suggested the use of
the information to evaluate risk levels, while Schauss taught a medical diagnostic
analysis system that evaluates patient data obtained from medical testing or patient
questioning for drugs contraindications. (Id. at 58.) The Examiner concluded that it
would have been obvious to one of ordinary skill in the art at the time of the invention
to implement the screening for drug contraindications suggested in Elsayed et al. with
the method of Schauss et al., since Schauss et al. teach the particular steps for
performing the analysis. (Id. at 58.) Regarding Claim 6, the Examiner stated that
although Elsayed does not specifically teach that data received by facsimile
transmission is entered by an OCR software, it is inherent that this data must be
entered into database. (Id. at 58.) The Examiner also objected to Claims 2832 as
being dependent upon a rejected base claim, but would be allowable if rewritten in
independent form. (Id. at 59.)
1
Except for the prosecution history, exhibit cites herein are directed to the internal
page numbers of the exhibit, rather than to the Exhibits Bates numbers.
7

In response, applicants amended Claim 1 by adding, among other limitations,
upon a determination that said risk is acceptable, generating a prescription approval
code to be retrieved by said pharmacy before said prescription is filled. (Id. at 87.)
Based on this amendment, applicants argued that Elsayed, although teaching a
method which contains many of the steps of the present invention, contains no
disclosure of the generation of a prescription approval code as recited in amended
Claim 1. (Id. at 85.) Applicants further argued that [a]lthough Schauss may describe
a medical diagnostic analysis system that evaluates patient data obtained from
questioning a patient or medical testing, Schauss contains no disclosure remotely
related to the generation of a prescription approval code, this being the subject of
Applicants claims. (Id. at 86.)
In response, the Examiner rejected the claims as obvious over Elsayed in view of
Schauss and Boyer, U.S. Patent No. 6,202,923 (Ex. 1005, Boyer ), which includes a step
for generating a prescription number or code associated with said prescription by a
computer workstation. ( Id. at 9192.)
In response, applicants argued:
As amended on March 23, 2001, Claim 1 further requires an assessment,
based upon the risk group assignment and the information collected
from the patient, as to whether the risk of the side effect occurring is
acceptable. Upon a determination that the risk is acceptable, and only upon
such a determination, a prescription approval code is generated, which must
be retrieved by the pharmacy before the prescription may be filled. Thus,
8

the prescription approval code is not merely a number that is associated
with the prescription, but instead represents the fact that a determination
has been made that the risk of the side effect occurring is acceptable, and
that approvalan affirmative decisionhas been made for the
prescription to be filled. Boyer does not disclose or suggest such an
approval code.
(Id. at 10607.) Applicants further argued that in Boyer, the prescription number is
simply an identifier for the prescription, and is not an approval code, as recited in
Applicants claims, and that Boyer provides no indication that a prescription approval
code, as described and claimed in the instant application, must be generated and
retrieved by the pharmacist before the prescription may be filled. (Id. at 107.)
The applicants amended Claim 28 to be an independent claim, and then argued
that because [a]ny proper combination of the disclosure of Boyer with that of
Elsayed and Schauss does not teach or suggest the invention defined by Applicants
claims, the Examiner should withdraw the 103 rejection. (Id. at 10607.)
After this response, all of the 720 Patent claims were allowed. (Id. at 111.)
B.
Claim Construction of Challenged Claims

A claim subject to IPR receives the broadest reasonable construction in light
of the specification of the patent in which it appears. 37 C.F.R. 42.100(b); see In re

Cuozzo Speed Techs., LLC, 778 F.3d 1271, 1279 (Fed. Cir. 2015). In applying such a
standard, the broadest reasonable construction of claim language is not one that
permits any reading, but instead is one that must be made in light of the specification
9

as it would be interpreted by one of ordinary skill in the art. In re Am. Acad. of Sci.
Tech. Ctr., 367 F.3d 1359, 1364 (Fed. Cir. 2004) (citation omitted).
Unless otherwise noted, Petitioner accepts, for purposes of IPR only, that the
claim terms of the 720 Patent are presumed to take on the ordinary and customary
meaning that they would have to one of ordinary skill in the art. 2
1.
Consulted
Consulted means accessed and considered. (Ex. 1030 at 3; Ex. 1027 39.)
2.
Teratogenic effect
Teratogenic effect means any effect that disturbs the normal growth and
development of an embryo or fetus. (Ex. 1030 at 2; Ex. 1027 40.)
Petitioner notes that, in some instances, the patentee has defined claim terms apart
from their plain meaning. See Pacing Techs., LLC v. Garmin Intl, Inc., 778 F.3d 1021,
1024 (Fed. Cir. 2015). These terms include drug, computer readable storage
medium, patient risk groups, risk parameters, risk group assignment, likely to
occur, prescription approval code, counseled, risk avoidance measures, and
informed consent. (Ex. 1001 at 3:3538, 3:4548, 4:5456, 5:2933, 6:307:19,
8:4557, 9:826, 10:4146, 13:4464.)
10

3.
Adverse side effect
Adverse side effect means any unfavorable abnormality, defect, mutation,

lesion, degeneration or injury which may be caused by taking the drug. (Ex. 1030 at
3; Ex. 1027 41; see Ex. 1001 at 3:3844.)
C.
Statement of Precise Relief Requested for Each Claim Challenged

1.
Claims for Which Review is Requested
Petitioners request IPR under 35 U.S.C. 311 of Claims 132 of the 720
Patent, and cancellation of these 32 claims as unpatentable.
2.
Statutory Grounds of Challenge
Petitioners request IPR of Claims 132 of the 720 Patent in view of the
following references, each of which is prior art to the 720 Patent under 35 U.S.C.
102(a) and (b) or 103. The Examiner did not reference any of the prior art listed in
the following chart in any Office Action. (See generally, Ex. 1002.) Claims 132 are
unpatentable under 35 U.S.C. 103:
Ground Proposed Rejections for the 720 Patent
Exhibit Number(s)
1
Claims 132 are obvious under 35 U.S.C. 103(a) in 1007, 1008, and
1010
view of Mitchell (Ex. 1010), Dishman (Ex. 1007), and
Cunningham (Ex. 1008).
D.
Overview of the State of the Art and Motivation to Combine

By October of 2000, it was well recognized in the art that teratogenic drugs
which can cause birth defectsneeded to be regulated. (See, e.g., Ex. 1006 at 90104;
11

Ex. 1010 at 10105.) The central regulatory goal was to avoid pregnancy in patients
treated with the drug. (See, e.g., Ex. 1010 at 101.) One notable case of a drug marketed
through methods to prevent its use in pregnant patients is isotretinoin, marketed
under the trade name Accutane. (See Ex. 1010 at 101.) Rather than remove this drug
from the market once its teratogenicity was realized, isotretinoin became part of a
manufacturer-sponsored Pregnancy Prevention Program (PPP). (Ex. 1010 at 101.)
The program, among other features, included the distribution to physicians of a kit
that included informed consent documents and patient counseling information.
(Ex. 1010 at 101.) In particular, patients were warned against the teratogenic risk of
isotretinoin and the need to prevent pregnancy. (Ex. 1010 at 105.) Patients were also
advised as to effective available methods of birth control. (See Ex. 1010 at 103.)
Thalidomide is a drug that originated in Germany in 1957. (Ex. 1001 at 1:40
41.) Doctors initially prescribed the drug as a sedative, but quickly noticed its
effectiveness in treating a form of leprosy, erythema nodosum leprosum (ENL), as
well. (Ex. 1011 at 32021.) However, shortly after thalidomide came on the market,
doctors realized that the drug caused severe birth defects in infants whose mothers
took the drug while pregnant. (Ex. 1011 at 320.) As a result, thalidomide was generally
taken off of most markets by 1962. (Ex. 1001 at 1:4445.) Due to thalidomides
therapeutic effects, the drug was reintroduced in the United States in the 1990s with
the understanding it could be marketed only with strict controls, and gained FDA
approval to treat ENL in 1998. (See Ex. 1006 at 901; Ex. 1011 at 320.)
12

Doctors and pharmacists interested in bringing thalidomide to the market with
restrictions to protect from its teratogenic effects considered the Accutane PPP, with
its focus on counseling, as a starting point. (Ex. 1012 at 11011; see Ex. 1014 at 1.)
They also considered modeling a thalidomide program on experiences with other
hazardous drugs, including clozapine (trade name Clozaril). (Ex. 1012 at 11112.)
As early as 1997, medical professionals observed that the prescription control
methods for clozapine, an anti-depressant with potential adverse effects indicated by
white blood cell counts (WBCs), could be copied for thalidomide. (Ex. 1012 at
112.) In particular, these prescription control methods included keeping records of
patients taking the drug, as well as physicians and pharmacists pre-approved to
prescribe and dispense the drug. (Ex. 1007 at 899900; see Ex. 1012 at 11519;
Ex. 1014 at 9, 24.) The clozapine patients were additionally required to submit to
weekly WBC testing and could only have a prescription for clozapine filled if the test
results fell within a pre-designated range. (Ex. 1007 at 899; see Ex. 1012 at 112;
Ex. 1014 at 8.)
It was also well known in the art prior to 2000 that prescription records can
be kept in a computerized system. (See, e.g., Ex. 1015 at 174; Ex. 1016 at 56, 6063,
68; Ex. 1027 56.) Such records would include information about the patient such as
their sex, height, weight, allergies, and other health-related measures. (See Ex. 1016 at
59; Ex. 1027 56.) Physicians and pharmacists had used computerized systems to
track their patients since at least 1975. (See, e.g., Ex. 1016 at 53; Ex. 1015 at 174, 182
13

83.) Practitioners then used this data to determine (1) whether to prescribe a drug to a
particular patient, and (2) how long a patient should take the medication. (See Ex. 1016
at 53, 6367.)
Thus, in the case of thalidomide or any teratogenic drug, those of ordinary skill
in the art would have beenand indeed weremotivated to combine the method
for avoiding pregnancy with a computerized tracking system that only permits filling
prescriptions for the drug when certain conditions (e.g., non-pregnancy) are met. (See
Ex. 1033 at 1136 (Celgene has drafted a plan that it hopes will prevent fetal exposure
to the drug. The plan is built on experience with restrictions on such other drugs
with severe adverse effects as Accutane , used to treat severe acne, and Clozaril
, used to treat schizophrenia [and] a tracking system would be in place to ensure
compliance.); Ex.1012 at 11112; Ex. 1027 5960.)
1.
Summary of the Petitions Prior Art References

a.
Mitchell (Ex. 1010)
Mitchell constitutes prior art under 35 U.S.C. 102(b) because it was published
in 1995. (Ex. 1010 at Cover.) During prosecution of the 720 Patent, the examiner did
not consider this reference. (See Ex. 1001 at Cover.)
Mitchell discloses a pregnancy prevention program implemented to minimize
pregnancies among women treated with the known teratogenic drug isotretinoin. (See
Ex. 1010 at 10105.) The program sought to keep the drug available while
minimizing the teratogenic hazard. (Id. at 105.) Additionally, the programtargeted
14

at both prescribers and patientsinstructed prescribers to warn patients of risks,
obtain negative pregnancy tests, and delay therapy until the second or third day of the
next normal menstrual period. (Id. at 101.) The program also provided materials to
patients such as information brochures and contraceptive information. (Id. at 101.)
Mitchell also describes counseling patients in relation to isotretinoins
teratogenic effects. (Id. at 105.) Some implementations of the program included
warnings about the need to have a negative blood pregnancy test before starting
therapyand to use effective birth control one month before starting therapy, during
therapy, and one month after completing it. (Id. at 103.)
b.
Dishman (Ex. 1007)
Dishman constitutes prior art under 35 U.S.C. 102(b) because it was published
in 1989. (Ex. 1007 at 899.) During the prosecution of the 720 Patent, the examiner
did not consider this reference. (See Ex. 1001 at Cover.)
Dishman discloses a program for controlling the dispensing of clozapine, an
antipsychotic drug, to veterans. (Ex. 1007 at 899.) Clozapine is associated with the
life-threatening side effect of agranulocytosis. (Ex. 1012 at 112.) Dishman describes a
monitoring program instituted by the Department of Veterans Affairs (VA) in 1991
to prevent contraindicated individuals from receiving clozapine. (Ex. 1007 at 900.)
Specifically, Dishman teaches that the VAs program established a National
Clozapine Coordinating Center (NCCC) to review each clozapine candidates file
before granting approval for use and weekly tracking. (Id. at 900.) Prior to this
15

approval, each patient underwent extensive evaluation and documentation to identify
contraindications, including pregnancy. (Id. at 900.) Additionally, for prescription or
use of clozapine, prescribers and patients had to register with the Clozaril National
Registry, which requires weekly monitoring of a patients white blood cell counts and
limits the quantity of medicine dispensed at one time. (Id. at 899.) This process
requires the cooperation and coordinated efforts of the patient, physician, laboratory,
and pharmacy. (Id. at 899.) The NCCC also mandated that each hospital have a
computerized clozapine prescription lockout system, which tied the hospitals
laboratory database to the outpatient pharmacy dispensing software. (Id. at 900.) Thus,
clozapine prescriptions could only be processed when certain pre-defined clinical
criteria were metspecifically, when white blood cell counts were within defined
limits. (Id. at 899.)
c.
Cunningham (Ex. 1008)
The Cunningham patent constitutes prior art under 35 U.S.C. 102(b) because it
was filed in 1995 and granted in 1998. (Ex. 1008 at Cover.) During the prosecution of
the 720 Patent, the examiner did not consider this reference. (See Ex. 1001 at Cover.)
The examiner did consider, but did not cite, a divisional of this reference. (See
Ex. 1001 at Cover; Ex. 1010 at Cover.)
Cunningham discloses a method of dispensing pharmaceutical product samples
by linking prescribers and pharmacies to a central computing station. (Ex. 1008 at
Cover.) Specifically, before filling any prescription for a pharmaceutical trial product,
16

the pharmacy must upload defined information into the central computing station.
(See id. at 11:613.) Only if the central computing station establishes that the uploaded
information is valid can the central computing station issue a pharmacy approval code
for the pharmacy to then dispense the pharmaceutical product. (See id. at 11:1323.)
E.
Level of Ordinary Skill in the Art

A persona of ordinary skill in the art (POSA) in pharmaceutical prescriptions
as of October 23, 2000the earliest possible priority date for the 720 Patent
would typically have either a Pharm. D. or a BS in pharmacy with approximately 510 years of experience and a license to practice as a registered pharmacist in any one
or more of the United States. (Ex. 1027 16.) An ordinarily skilled artisan may
work as part of a multi-disciplinary team and draw upon not only his or her own
skills, but also take advantage of certain specialized skills of others on the team, to
solve a given problem and care for varying patient populations. (Ex. 1027 17.)
VI.
DETAILED EXPLANATION OF THE CHALLENGE
A.
Ground 1: Claims 132 of U.S. Patent No. 6,315,720 are obvious under
35 U.S.C. 103(a) over Mitchell in view of Dishman and in further
view of Cunningham and the knowledge of one of ordinary skill in the
art.
1.
Claim 1 is obvious over Mitchell in view of Dishman and in further

view of Cunningham .
Claim 1 of the 720 Patent is written in Jepson format, meaning that the claim
first describes the scope of the prior art and then claims an improvement over the
17

prior art. Dow Chem. Co. v. Sumitomo Chem. Co., 257 F.3d 1364, 1368 (Fed. Cir. 2001).
Specifically, the Claim 1 preamble recites:
In a method for delivering a drug to a patient in need of the drug, while
avoiding the occurrence of an adverse side effect known or suspected of
being caused by said drug, wherein said method is of the type in which
prescriptions for said drug are filled only after a computer readable
storage medium has been consulted to assure that the prescriber is
registered in said medium and qualified to prescribe said drug, that the
pharmacy is registered in said medium and qualified to fill the
prescription for said drug, and the patient is registered in said medium
and approved to receive said drug, the improvement comprising:
(Ex. 1001 at 18:1727 (emphasis added).) Because a preamble is impliedly admitted
to be prior art when a Jepson claim is used, the patentee has admitted that the Claim
1 preamble is prior art, rather than a point of novelty. Pentec, Inc. v. Graphic Controls
Corp., 776 F.2d 309, 315 (Fed. Cir. 1985); see In re Glatt Air Techniques, Inc., 630 F.3d
1026, 1028 (Fed. Cir. 2011) (rejecting a claim as obvious in view of the admitted
prior art from the claim preamble and a single cited reference).
An ordinarily skilled artisan, when seeking to treat patients with a drug known
or suspected of causing an adverse side effect as in Claim 1s preamble, would look to
Mitchell for guidance on an approach that seeks to keep the drug available while
minimizing the hazard, and would garner from its recommendations for
delivering a drug to a patient in need of the drug, while avoiding the occurrence of an
adverse side effect known or suspected of being caused by said drug, as the
18

preamble requires. (Ex. 1010 at 105; Ex. 1027 76.) See In re Icon Health & Fitness, Inc.,
496 F.3d 1374, 1380 (Fed. Cir. 2007) (One skilled in the art would naturally look to
prior art addressing the same problem as the invention at hand, and in this case would
find an appropriate solution.).
With respect to Claim 1 of the 720 Patent, an ordinarily skilled artisan would
understand from Mitchell the desirability, when treating patients with drugs associated
with adverse side effects to certain risk groups, of defining a plurality of patient risk
groups based upon a predefined set of risk parameters for said drug as required by
Claim 1(a), defining a set of information to be obtained from said patient, which
information is probative of the risk that said adverse side effect is likely to occur if
said drug is taken by said patient as required by Claim 1(b), in response to said
information set, assigning said patient to at least one of said risk groups as required
by the first portion of Claim 1(c), and based upon said information and said risk
group assignment, determining whether the risk that said adverse side effect is likely
to occur is acceptable as required by Claim 1(d). (See Ex. 1010 at 10102, 105; Ex.
1027 78.)
Specifically, Mitchell teaches a patient-qualification checklist for assigning
patients to the risk groups to which a drug with teratogenic side effects, such as
isotretinoin, can and cannot be administered, as in Claim 1(a), based on the
unacceptable risk of teratogenic side effects to a fetus, as in Claim 1(d). (Ex. 1010 at
101; Ex. 1027 79, 94.) Mitchells risk group list includes, for example, women of
19

childbearing age and women who were at high risk of becoming pregnant, with
patients outside of these groups falling into a separate, lower risk category. (Ex. 1010
at 102, 105.) One of ordinary skill in the art would understand that a prescriber would
assign a patient to these various risk groups, as in the first portion of Claim 1(c), by
obtaining information from the patient such as their gender, and whether they are of
childbearing age or at a high risk of becoming pregnant, which are probative of
the risk that said adverse side effect is likely to occur if said drug is taken by said
patient, as in Claim 1(b). (Ex. 1010 at 102, 105; Ex. 1027 81.)
With respect to the second portion of Claim 1(c)entering said risk group in
said mediuman ordinarily skilled artisan would understand from Mitchell that
written records should be kept relating to risk group and related information.
(Ex. 1027 84.) For example, Mitchell recorded certain information via surveyenrollment consent forms. (Ex. 1010 at 102.) Although Mitchell does not explicitly
mention keeping these records in a computer readable storage medium, because
Mitchell published the aggregated patient risk group information collected, it would
have been obvious to one of ordinary skill in the art that Mitchell inherently entered
the risk group information in a computer readable storage medium. (Ex. 1027 86.)
See Par Pharm., Inc. v. TWi Pharms., Inc., 773 F.3d 1186, 11941195 (Fed. Cir. 2014)
(We have recognized that inherency may supply a missing claim limitation in an
obviousness analysis.). Additionally, it would have been obvious to an ordinarily
skilled artisan that electronic records of information such as the patient risk group
20

assignment would be useful and easy to achieve through the entry into a computer.
(Ex. 1027 85.) See Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348, 1364 (Fed. Cir. 2007)
(finding obviousness where the skilled artisan would have had that reasonable
expectation of success that [application of the prior art technique] would work for its
intended purpose.).
Like Mitchell, which teaches guidelines for tightly-controlling the dispensing of
isotretinoin, Dishman discloses a program for tightly controlling the dispensing of the
antipsychotic drug clozapine. (See Ex. 1007 at 899901.) Armed with the disclosure of
Mitchell, an ordinarily skilled artisan would have been motivated to look to the system
disclosed in Dishman to further implement a computerized registry for delivering a
drug to a patient in need of the drug, while avoiding the occurrence of an adverse side
effect known or suspected of being caused by said drug. (Ex. 1001 at 18:1618; Ex.
1027 88.) See Tyco Healthcare Grp. LP v. Ethicon Endo-Surgery, Inc., 774 F.3d 968, 977
(Fed. Cir. 2014) (When a claimed invention involves a combination of elements,
however, any need or problem known in the relevant field of endeavor at the time of
invention can provide a reason to combine.). Indeed, those of ordinary skill in the art
did look to the same isotretinoin system described in Mitchell with respect to the 720
Patent. (Ex. 1001 at 2:1335; Ex. 1033 at 1036.) See Rogers v. Desa Intl, Inc., 198 Fed.
Appx. 918, 922 (Fed. Cir. 2006) (Evidence that those of ordinary skill in the art in
fact combined the prior art teachings as claimed is certainly evidence that they were
21

motivated to do so. Such evidence shows the knowledge of the skilled artisan at the
time of the invention, which can provide the basis for a motivation to combine.).
With respect to the second portion of Claim 1(c)entering said risk group in
said mediumDishman discloses the storage of the patients clinical and
demographic information on a computer readable storage medium. (Ex. 1007 at
899.) For example, Dishman teaches that the NCCC requires that each hospital have a
computerized clozapine prescription lockout system[that] ties the hospitals
laboratory database to the outpatient pharmacy dispensing software. (Ex. 1007 at
900.) An ordinarily skilled artisan would have understood from the Dishman
reference that this computerized system must include the patients risk group
assignment data in order to determine which prescriptions should be locked out.
(Ex. 1027 91.) See Par Pharm., Inc., 773 F.3d at 11941195.
The final portion of the 720 Patents Claim 1Claim 1(e)requires that,
upon a determination that said risk is acceptable, generating a prescription approval
code to be retrieved by said pharmacy before said prescription is filled. (Ex. 1001 at
18:4042.) This mechanism would have been obvious to an ordinarily skilled artisan
upon reading Dishman, which discloses approval of acceptable risk through a registry
[that] permits community and hospital pharmacies to dispense clozapine only upon
the pharmacists verification that the WBC count is within acceptable limits. [T]he
lockout system prevents the filling of any clozapine prescription if the computer
22

notices three consecutive drops in WBC count. (Ex. 1007 at 899900; Ex. 1027
9596.)
Additionally, as the 720 Patent correctly states, [s]uitable computer readable
storage media will be apparent to one of ordinary skill in the art, once armed with
the teachings of the present application.) (Ex. 1001 at 5:1116.) An approval code
system such as that required by Claim 1(e)already known to those of ordinary skill
in the art at the timewould be an obvious mechanism for one of ordinary skill in
the art to use in order to implement Dishmans lockout system. (Ex. 1027 97.) See
Bayer Schering Pharma AG v. Barr Labs., Inc., 575 F.3d 1341, 1347 (Fed. Cir. 2009)
(When there is a design need or market pressure to solve a problem and there are a
finite number of identified, predictable solutions, a person of ordinary skill has good
reason to pursue the known options within his or her technical grasp. If this leads to
the anticipated success, it is likely the product not of innovation but of ordinary skill
and common sense.) (quoting KSR Intl Co. v. Teleflex Inc., 550 U.S. 398, 421 (2007).
It would have been further obvious to one of ordinary skill in the art to utilize
the Claim 1(e) approval codes to implement Dishmans lockout system, in light of
Cunninghams disclosure of an approval code lockout system for a pharmacy:
If authenticity is not established, it follows that the participating
pharmacy cannot dispense corresponding pharmaceutical product.
However, if authenticity is established then the pharmac[ys] terminal
dials the central computing station and data and information from the
pharmac[ys] authorization media and personal identification is uploaded
23

to the database of the central computing station 12. Assuming full
validation, the central computing station issues a pharmacy
approval code and the pharmacy records that approval code on the
actual presented product trial media 18. Once validation is established
the pharmacy then dispenses pharmaceutical trial product
(Ex. 1008 at 11:68, 1723 (emphasis added); Ex. 1027 98.) See KSR Int'l Co., 550
U.S. at 41617 (holding that where a straightforward combination of references
[s]imply arranges old elements with each performing the same function it had been
known to perform and yields no more than one would expect from such an
arrangement, the combination is obvious.) (internal quotations and citations
omitted).
In view of the guidelines for the avoidance of treating pregnant patients with
isotretinoin taught by Mitchell, it would have been obvious to an ordinarily skilled
artisan to implement the methods disclosed in Dishman and Cunningham to limit
dispensation of a drug associated with adverse effects to certain risk groups.
(Ex. 1027 99.) See Abbott Labs v. Andrx Pharms., Inc., 452 F.3d 1331, 1345 (Fed. Cir.
2006) (finding substantial question of invalidity because the combination of references
for the reduction of systemic side effects would not be surprising and would not be
unexpected.). Therefore, an ordinarily skilled artisan treating a patient with a
teratogenic or other risk-laden drug in accordance with the guidelines disclosed in
Mitchell would look to published methods for limiting dispensation of other drugs
such as the clozapine registry found in Dishman and the approval code system
24

taught by Cunninghamand would view Claim 1 of the 720 Patent obvious in view of
these three references. (Ex. 1027 100.) See Dystar Textilfarben GmbH v. C.H. Patrick
Co., 464 F.3d 1356, 1361 (Fed. Cir. 2006) (The motivation need not be found in the
references sought to be combined, but may be found in any number of sources,
including common knowledge, the prior art as a whole, or the nature of the problem
itself.).
2.
Dependent Claims 26 are obvious over the prior art of Ground 1,

further view of the knowledge of one of ordinary skill in the art.
Claims 26 depend from Claim 1, and merely add limitations already known in
the field and obvious to one of ordinary skill in the art. Claim 2 requires that in
response to said risk group assignment, said patient is counseled as to the risks of
taking said drug and advised as to risk avoidance measures, while Claim 3 requires
that the Claim 2 counseling comprises full disclosure of said risks, Claim 4 requires
that said prescription is filled only following [the Claim 3] full disclosure and
informed consent of said patient, Claim 5 requires that said risk group assignment
and [Claim 4] informed consent is verified by said prescriber at the time that said
patient is registered in said computer readable storage medium, and Claim 6 requires
that said risk group assignment and said informed consent is transmitted to [the
Claim 5] computer readable storage medium by facsimile and interpreted by optical
character recognition software. (Ex. 1001 at 18:4358 (emphasis added).)
25

Mitchell teaches that the disclosed program encourages communication
between physicians and patients regarding the drugs teratogenic risk and the need to
prevent pregnancy, and that physicians were further provided with guidelines:
instructing them, for example, to warn patients of risks, obtain negative
pregnancy tests, and delay therapy until the second or third day of the
next normal menstrual period. They also included a patient-qualification
checklist, an information brochure for patients, contraceptive
information, information about and the necessary forms for a
contraception referral program (in which the manufacturer would
reimburse patients for a visit to another physician for contraceptive
counseling, and a consent form.
(Ex. 1010 at 101 (emphasis added), 105.) Mitchell additionally discloses that:
the manufacturer replaced traditional medication bottles with a 10capsule blister pack that contained information directed specifically at
women: the package included warnings about the risks of becoming
pregnant while taking isotretinoin or during the month after treatment,
an avoid pregnancy icon behind each capsule, and line drawings of
malformations associated with isotretinoin.
(Ex. 1010 at 101.) This information meets the counseling and disclosure requirements
of Claims 2 and 3. (Ex. 1027 104.)
In addition to the consent form contained in the physician information
discussed above, Mitchell further teaches of the need for patient consent and that
the program also included survey-enrollment consent forms. (Ex. 1010 at 102, 105.)
26

These teachings meet the disclosure and informed consent treatment prerequisites of
Claim 4.
Additionally, because Mitchell teaches that [t]he enrollment forms were
screened on receipt to exclude enrollments that were apparently fraudulent, men, and
previously enrolled women, and then [t]he eligible women were assigned, at
random, to be followed by one of the two methods, it would have been obvious to
one of ordinary skill in the art that the prescribing doctor would have verified the
disclosed requirements for treatmentsuch as the patients informed consent and risk
group assignmentwhen screening the enrollment forms and registering the patient
in the database for following. (Ex. 1010 at 102; Ex. 1027 10708.) Dishman further
renders this Claim 5 verification obvious, teaching that:
the pharmacist screens potential candidates before they undergo
extensive evaluation. The screening involves reviewing the patients case
with the requesting practitioner, reviewing the patients file, and
interviewing the patient to ensure that the patient and family members
are committed to weekly blood tests and follow-up. This screening
ensures that the physician does not waste time evaluating patients who
are ineligible for clozapine therapy. After a patient has been
determined eligible for clozapine therapy, the pharmacist forwards all
pertinent information to the NCCC. After NCCC approval, the
pharmacist enrolls the patient into the hospitals clozapine tracking
system, and clozapine therapy is begun.
(Ex. 1007 at 900 (emphasis added); Ex. 1027 10910.)
27

The previous disclosure also renders obvious to one of ordinary skill in the art
that the informed consent, risk group assignment, and other portions of the patients
file in the Dishman system are transmitted to the NCCCs database described above
with respect to Claim 1(c), and as required by the first portion of Claim 6. (Ex. 1027
112.) Dishman further teaches that, [a]fter each weekly follow-up appointment, the
pharmacist faxes a tracking sheet containing an evaluation of the patient to the
NCCC. (Ex. 1007 at 901.) Because it was within the knowledge of one of ordinary
skill in the art to transfer paper data into a computer database by fax, which is then
interpreted by optical character recognition [OCR] software, it would have been
obvious to one of ordinary skill in the art that the Dishman system would have used
OCR software to load the tracking sheet information into the NCCC database
(Ex. 1027 114.) Consequently, [i]t also would have been obvious to an ordinarily
skilled artisan that paper risk group assignments and informed consents could
similarly be transferred to the database through fax and OCR, as the last portion of
Claim 6 requires. (Ex. 1027 114.) See Perfect Web Techs., Inc. v. InfoUSA, Inc., 587 F.3d
1324, 1329 (Fed. Cir. 2009) (KSR expanded the sources of information for a properly
flexible obviousness inquiry to include the background knowledge, creativity, and
common sense of the person of ordinary skill.).
28

3.
Claims 710 depend from Claim 1, and merely add limitations already known
in the field and obvious to one of ordinary skill in the art. Claim 7 requires that the
information to be obtained from said patient prior to treatment includes the
results of diagnostic testing, while Claims 8, 9, and 10 respectively require that the
diagnostic testing is probative of the onset of said adverse side effect, is probative
of the concentration of said drug in a tissue of said patient, and comprises genetic
testing. (Ex. 1001 at 18:5967.)
Both Mitchell and Dishman disclose extensive diagnostic testing, including testing
probative of the onset of said adverse side effect, prior to treatment. Thus, both
Mitchell and Dishman teach the limitations of Claims 7 and 8. Specifically, Mitchell
teaches warnings about the need to have a negative blood pregnancy test before
starting therapy since birth malformations [are] associated with isotretinoin.
(Ex. 1010 at 101, 103.) Additionally, Dishman discloses that [t]he NCCC guidelines
require extensive patient evaluation and documentation. A complete physical
examination, including laboratory testing and electrocardiographic analysis, is
required. (Ex. 1007 at 900.)
With respect to Claim 9, it would have been obvious to one of ordinary skill in
the art to include, within the extensive diagnostic testing taught by Mitchell and
Dishman, testing for the drug concentration in patient tissue. (Ex. 1027 12223.)
29

Specifically, for any patient that had previously been treated with the drug, it would
have been obvious to one of ordinary skill in the art to conduct diagnostic testing
probative of the concentration of the drug remaining in the patients body. (Ex. 1027
122.) However, because many drugs do not generally distribute uniformly in the
body, but instead are preferentially absorbed by certain body tissues, one of ordinary
skill in the art would have further recognized the importance of performing diagnostic
testing that would be probative of the concentration of such a non-uniformly
distributing drug in the drugs target tissues. (Ex. 1027 12223.) See Tyco Healthcare
Group LP, 774 F.3d 968, 977 (Claims would have been obvious if they are nothing
more than a combination of familiar elements that yield predictable results.).
With respect to Claim 10, it would have been further obvious to one of
ordinary skill in the art to include genetic testing in the extensive diagnostic testing
taught by Mitchell and Dishman. (Ex. 1027 125.) Specifically, it was common in the
art at the time of the 720 Patent to conduct genetic testing at the same time as the
pregnancy testing taught in Mitchell. (Ex. 1027 124.) Similarly, [b]ecause there is
frequently a genetic component in schizophreniathe ailment treated in Dishman
one of ordinary skill in the art would have expected that the extensive diagnostic
testing in Dishman would have included genetic testing. (Ex.1027 126.) More
generally, because genetic testing was a well-known diagnostic procedure at the time
of the 720 Patent, it would have been obvious to one of ordinary skill in the art to
include genetic testing in the diagnostic testing that preceded such last-resort
30

treatments as those disclosed in Mitchell and Dishman. (Ex. 1027 127.) See Unigene
Labs., Inc. v. Apotex, Inc., 655 F.3d 1352, 1361 (Fed. Cir. 2011) (This court has
observed that teachings from prior art, suggestions beyond the literal teachings of
those art references, or even motivations from the store of common knowledge of
one of ordinary skill in the art field (TSM)flexibly viewed and appliedprovide
the sources of evidence that an ordinary skilled artisan might have found and
combined at the time of the invention.).
4.
Dependent Claims 1114 and 2025 are obvious over the prior art of
Ground 1, and more specifically over Mitchell in view of the
knowledge of one of ordinary skill in the art.
Claims 1114, and 2125 depend from Claim 1, and merely add limitations
already known in the field and obvious to one of ordinary skill in the art. Claims 11,
12, and 13 respectively require that the drugs associated side effect is likely to arise
in said patient, is likely to arise in a foetus carried by said patient, and is likely to
arise in a recipient or a foetus carried by a recipient of the bodily fluid of said patient,
while Claim 14 requires that the claim 12 recipient is a sexual partner of said
patient. (Ex. 1001 at 19:19.) Claim 22 requires that the drug is thalidomide. (Ex.
1001 at 19:3435.) Claim 21 requires that the drugs associated side effect comprises
a teratogenic effect, while Claims 23 and 24 respectively require that the Claim 21
teratogenic effect is likely to arise in a foetus carried by said patient, and is likely to
arise in a foetus carried by a recipient of the bodily fluid of said patient and Claim 25
requires that the Claim 24 recipient of the bodily fluid of said patient is a sexual
31

partner of said patient. (Ex. 1001 at 19:3233, 3642.) Claim 20 requires providing
said patient with a contraceptive device or formulation. (Ex. 1001 at 19:3031.)
Although Mitchell does not explicitly disclose that isotretinoins side effects arise
in the patient taking the drug, Mitchell discloses that its study relates to the drug
Accutane. (Ex. 1010 at 101.) One of ordinary skill in the art would have known to
look to Accutanes publicly-available FDA-approved drug label (included as a package
insert with any prescription of the drug) to determine whether isotretinoins side
effects arise in the patient taking the drug. (Ex. 1027 132.) The Accutane label prior
to the 720 Patents October 2000 filing stated in bold: WARNINGS: Psychiatric
Disorders: Accutane may cause depression, psychosis and rarely, suicidal ideation,
suicide attempts and suicide. (Ex. 1029 at 11.) Thus, [f]rom Mitchells disclosure, it
would have been obvious to one of ordinary skill in the art that isotretinoin side
effects arise in the patient taking the drugin the case of psychiatric disordersand
also in a fetus carried by the patient taking the drugin the case of teratogenicity,
satisfying Claims 11, 12, 21, 22 and 23. (Ex. 1010 at 101; Ex. 1027 134.)
By the time the 720 Patent was filed, it was well known to those of ordinary
skill in the art that certain drugs, including thalidomidedisclosed in Mitchell as a
drug that could potentially utilize Mitchells isotretinoin regimecould be found in
semen, and thus could be transmitted to a sexual partner of a male undergoing
treatment with the drug. (Ex. 1010 at 105; Ex. 1027 135.) For example, by 1982,
Mann and Lutwak-Mann had discovered that:
32

Thalidomide and tetracycline are drugs known to be strongly absorbed
by spermatozoa. Experiments indicating that thalidomide administered
to male rabbits adversely affects the pregnancy of females mated to these
males, for the first time drew attention to the until then unrecognized
eventuality of drug-induced pregnancy-wastage occurring by the paternal
route. Subsequently, it was shown that when [14C]thalidomide is
administered to male rabbits, the presence of the radioactive label can be
demonstrated in the semen (collected within the artificial vagina) within
a short time after ingestion, and is still detectable there some 12 days
later.
(Ex. 1018 at 78 (emphasis added).) Additionally, in 1997, Vanchieri wrote that
[b]ecause of a recent study showing thalidomide in rabbit semen and uncertainty
about its presence in human semen, both women and men receiving the drug will be
required to use contraception. (Ex. 1019 at 1.) For this reason, it was obvious to one
of ordinary skill in the art that a teratogenic drug, such as thalidomide, was likely to
cause side effects either in a sexual partner of a male being treated with the drug as in
Claims 14, 24, and 25, or in the fetus of this sexual partner as in Claims 13 and 23.
(Ex. 1027 13738.) See Perfect Web Techs., Inc., 587 F.3d at 1328 (Common sense
has long been recognized to inform the analysis of obviousness if explained with
sufficient reasoning.).
The teratogenic risks associated with isotretinoin had been well known since
the 1980s, as Mitchell discusses at length. (Ex. 1010 at 101 (The concern about
human teratogenicity proved well founded reports of pregnancies in exposed
33

women continued to accumulate, and by 1989 approximately 78 malformed infants
had been reported.).) For this reason, those of ordinary skill in the art at the time of
the 720 Patent readily recognized the importance of contraception to patients taking
isotretinoin. (Ex. 1027 142.) This is why Mitchells Pregnancy-Prevention Program
in Women of Childbearing Age Receiving Isotretinoin taught an aggressive
program designed to reduce the risk of pregnancy among women taking the drug
that included warnings about the need to have a negative blood pregnancy test
before starting therapy; to wait until the next menstrual period before starting therapy;
and to use effective birth control one month before starting therapy, during therapy,
and one month after completing it. (Ex. 1010 at 101, 103.) Mitchell further taught
providing an information brochure for patients, contraceptive information,
information about and the necessary forms for a contraception referral program (in
which the manufacturer would reimburse patients for a visit to another physician for
contraceptive counseling). (Ex. 1010 at 101.) In light of Mitchells teachings, it would
have been obvious to one of ordinary skill in the art that when the patient
participates in the contraception referral program, that doctor will likely provide the
patient with a contraceptive device or formulation as in Claim 20, in order to
accomplish Mitchells objective of ensuring that women of childbearing age taking
isotretinoin use effective contraception. (Ex. 1010 at 102; 1027 145.) See Sciele
Pharma, Inc., 684 F.3d at 1259. See Sciele Pharma, Inc. v. Lupin Ltd., 684 F.3d 1253, 1259
(Fed. Cir. 2012) (finding substantial question of validity because, [i]f a person of
34

ordinary skill can implement a predictable variation, 103 likely bars its
patentability) (quoting KSR, 550 U.S. at 417).
5.
Dependent Claim 15 is obvious over the prior art of Ground 1, and

more specifically over Mitchell in view of Dishman and in further
view of the knowledge of one of ordinary skill in the art.
Claims 15 depends from Claim 1, and merely add limitations already known in
the field and obvious to one of ordinary skill in the art. Claim 15 requires f. defining
for each said risk group a second set of information to be collected from said patient
on a period basis; g. obtaining said second set of information from said patient; and h.
entering said second set of information in said medium before said patient is
approved to receive said drug. (Ex. 1001 at 19:1018.)
Both Mitchell and Dishman explicitly disclose defining information to be
collected and obtaining that information from the patient on a periodic basis as in
Claim 15(f) and (g). For example, Mitchell discloses that:
Each week, 100 women were randomly assigned to the group
interviewed by telephone. They were contacted three times: at the start
of therapy (within one month after enrollment), when we inquired about
the patients understanding of the hazards of isotretinoin and
compliance with the program; in the middle of therapy (between two
and four months after the start of the isotretinoin), when we inquired
about continued understanding of the hazards of isotretinoin and
compliance with the program; and six months after the completion of
therapy, when we asked about the occurrence of pregnancy during or
after treatment.
35

(Ex. 1010 at 102.) In addition, Mitchell teaches that:
Women not randomly assigned to the telephone group were sent a brief
questionnaire six months after starting isotretinoin to determine the date
on which they had completed or were expected to complete therapy.
They were then mailed a questionnaire six months after that date, which
included the same questions as the third telephone interview.
(Ex. 1010 at 102.) Mitchell further teaches that, [t]o minimize memory loss and biased
recall, we collected information on the behavior of physicians and patients at the start
of therapy as well as during treatment. (Ex. 1010 at 102.) Additionally, Dishman
teaches that [t]he manufacturer, Sandoz, requires all prescribers and patients to be
registered with the Clozaril National Registry, which requires weekly monitoring of
each patients white blood cell (WBC) count and limits medication dispensing to a
one-week supply. (Ex. 1007 at 899.)
Dishman further discloses that [p]hysicians at the NCCC review each clozapine
candidates file before granting approval for use and review weekly tracking sheets
that report patient status. [T]he pharmacist ensures that the psychiatry resident
orders the necessary laboratory tests, performs the required clinical evaluation, and
documents the results in a weekly tracking sheet, which the pharmacist forwards to
the NCCC. (Ex. 1007 at 900 (emphasis added).) As previously discussed above with
respect to the second portion of Claim 1(c)Dishman discloses the storage of the
patients weekly WBC count (and other collected information contained in the weekly
tracking sheet) on a computer readable storage medium. (See Ex. 1007 at 899.)
36

Because Dishman also teaches that this weekly review occurs before granting approval
for use, and that its lockout system will allow clozapine prescriptions to be
processed only when WBC counts are within the defined limits, it would have been
obvious to one of ordinary skill in the art that the weekly WBC test results must be
entered in the medium before said patient is approved to receive said drug, as
required by Claim 15(h). (Ex. 1007 at 900; Ex. 1027 15354.) See Perfect Web Techs.,
Inc., 587 F.3d at 1328.
6.
Claims 1617 depend from Claim 1, and merely add limitations already known
in the field and obvious to one of ordinary skill in the art. Claim 16 requires that the
Claim 15 second set of information collected on a periodic basis comprises a survey
regarding said patients behavior and compliance with said risk avoidance measures,
while Claim 17 requires that the Claim 16 survey is conducted telephonically using
an integrated voice response system. (Ex. 1001 at 19:1924.)
Mitchell explicitly discloses Claim 16s requirement of a survey regarding said
patients behavior and compliance with said risk avoidance measures. For example,
Mitchells authors designed and conducted a survey to assess the compliance of
physicians and patients with the program and to identify the rate of pregnancy during
treatment with isotretinoin and during the month after treatment. (Ex. 1010 at 101
02.) Early in 1992, the questionnaire was modified to allow more complete
37

information to be obtained regarding sexual activity and birth control. (Ex. 1010 at
103.) Mitchell further discloses that, [a]mong women enrolled in this survey,
understanding of the teratogenic risks of isotretinoin and of the need to avoid
pregnancy was virtually universal. Compliance with other aspects of the program was
less complete, although in no case did compliance for any measure decline during the
study period. (Ex. 1010 at 104.)
Further, because one method of conducting the surveys in Mitchell was by
telephone, using an integrated voice response systemwhich was well known to
those of ordinary skill in the art at the timeas required by Claim 17, would have
been obvious to one of ordinary skill in the art. (Ex. 1027 158-61; see, e.g., Ex. 1017
at 61112, 623.) See In re Venner, 262 F.2d 91, 95 (C.C.P.A. 1958) (Furthermore, it is
well settled that it is not invention to broadly provide a mechanical or automatic
means to replace manual activity which has accomplished the same result.).
7.
Dependent Claims 1819 and 2627 are obvious over the prior art
of Ground 1, and more specifically over Mitchell in view of
Dishman and in further view of the knowledge of one of ordinary
skill in the art.
Claims 1819 and 2627 depend from Claim 1, and merely add limitations
already known in the field and obvious to one of ordinary skill in the art. Claim 18
requires that, where the patient is a female of childbearing potential, the Claim 15
second set of information collected on a periodic basis comprises the results of a
pregnancy test, while Claim 19 requires that the periodic interval for the Claim 18
38

pregnancy test comprises about 28 days. (Ex. 1001 at 19:2529.) Claim 26 similarly
requires that, where the drug has a teratogenic effect, the information to be obtained
from said patient includes the results of a pregnancy test, while Claim 27 adds to
the requirements of Claim 26 that said prescription is filled for no more than about
28 days. (Ex. 1001 at 19:4320:2.)
Mitchell explicitly discloses that, in light of isotretinoins teratogenicity,
women were warn[ed] about the need to have a negative blood pregnancy test before
starting therapy and that 78 percent [of women] were told to wait for pregnancytest results before starting isotretinoin as Claim 26 requires. (Ex. 1010 at 101
03.)
Mitchell further teaches obtaining periodic pregnancy test results from women
of childbearing age after isotretinoin treatment has begun: To identify compliance
with the program and the occurrence of pregnancy, the survey covered the treatment
period and the subsequent six months, a period long enough to allow identification of
pregnancies occurring as late as the first month after discontinuation of treatment.
(Ex. 1010 at 102 (emphasis added).) Mitchell also discloses that six months after the
completion of therapy, [the authors] asked about the occurrence of pregnancy during
or after treatment, and learned that there were 402 pregnancies during therapy.
(Ex. 1010 at 10102.) Dishman similarly teaches that, contraindications to clozapine
therapy include pregnancy, and so it would have been obvious to one of ordinary
39

skill in the art to also require a mid-treatment pregnancy test for Dishmans clozapine
patients upon a missed period. (Ex. 1007 at 900; Ex. 1027 167.)
Although neither reference teaches requiring periodic pregnancy tests before
prescribing the next cycle of drugs, Dishman does teach requiring WBC tests every
week before prescribing the next week of drugs, as discussed above with respect to
Claim 15(h). (Ex. 1007 at 899 (The manufacturer, Sandoz, requires all prescribers
and patients to be registered with the Clozaril National Registry, which requires
weekly monitoring of each patients white blood cell (WBC) count and limits
medication dispensing to a one-week supply.).) In light of Mitchell s requirement for
excluding pregnancy by a negative blood pregnancy before starting therapy it would
have been obvious to one of ordinary skill in the art to apply Mitchells pregnancy test
requirement to Dishmans periodic testing before prescription requirement, satisfying
Claim 18. (Ex. 1010 at 103; Ex. 1027 169.) See KSR Intl Co., 550 U.S. at 417.
Although Dishmans system requires testing every 7 days, and correspondingly
only allows patients to fill 7-day supply prescriptions, it was well known to one of
ordinary skill in the art that women may only become pregnant once during every 28day menstrual cycle. In light of this fact, when implementing Dishmans periodic
testing requirement to pregnancy testing, it would have been obvious to one of
ordinary skill in the art that the proper testing period for pregnancy is about 28 days,
as Claim 19 requires. (Ex. 1027 170.) See Sciele Pharma, Inc., 684 F.3d at 1259.
Further, applying Dishmans one-to-one correspondence between testing intervals
40

and prescription supplies, it would consequently have been obvious to one of
ordinary skill in the art to fill prescriptions for no more than about 28 days, as in
Claim 27. (Ex. 1027 171.) See KSR Intl Co., 550 U.S. at 417 ([I]f a technique has
been used to improve one device, and an ordinarily skilled artisan would recognize
that it would improve similar devices in the same way, using the technique is obvious
unless its actual application is beyond his or her skill.).
8.
The added limitations of independent Claim 28 and dependent

Claims 2932 are obvious over Mitchell in view of Dishman and in
further view of Cunningham and knowledge of one of ordinary
skill in the art.
Claim 28, although an independent claim, merely repeats the language of Claim
1 with a single added limitation already known in the field and obvious to one of
ordinary skill in the art. Claims 2932 depend from Claim 28, and similarly add
limitations already known in the field and obvious to one of ordinary skill in the art.
Claim 28(a)(e) maps precisely to Claim 1(a)(e), and so is obvious for the
reasons explained above with respect to Claim 1(a)(e). In addition, Claim 28 requires
that said adverse side effect is likely to arise in patients who take said drug in
combination with at least one other drug. (Ex. 1001 at 20:331.) Claims 29 and 30
respectively require that the information to be obtained from said patient is also
probative of the likelihood that said patient may take said drug and said other drug in
combination, and includes the results of diagnostic testing, while Claims 31 and
32 respectively require that the Claim 30 diagnostic testing comprises testing for
41

evidence of the use of said other drug and comprises testing for evidence which is
indicative of the onset of said adverse event. (Ex. 1001 at 20:3242.)
It would have been obvious to one of ordinary skill in the art that the adverse
effects described in Mitchell and Dishmanteratogenicity and agranulocytosis
would have also been likely to arise in patients who take said drug in combination
with at least one other drug, as required by Claim 28. (Ex. 1010 at 101; Ex. 1007 at
899; Ex. 1027 175.) See Perfect Web Techs., Inc., 587 F.3d at 1328.
As previously discussed with respect to Claims 7 and 8, both Mitchell and
Dishman disclose extensive diagnostic testing, including testing indicative of the onset
of said adverse side effect, prior to treatment. Thus, both Mitchell and Dishman teach
the limitations of Claims 30 and 32. Specifically, Mitchell teaches the need to have a
negative blood pregnancy test before starting therapy because of the drugs
teratogenic risk. (Ex. 1010 at 103, 105.) Additionally, Dishman discloses that [t]he
NCCC guidelines require extensive patient evaluation and documentation. A
complete physical examination, including laboratory testing and electrocardiographic
analysis, is required. (Ex. 1007 at 900.)
With respect to Claims 29 and 31, it was well known to those of ordinary skill
in the art at the time of the 720 Patent that the interactions among drug
combinations, also termed drug-drug interactions, could cause serious and even
lethal adverse side effects. (Ex. 1027 180.) For example, in 1983, Shinn states that
[d]rug [i]nteractions are a clearly defined problem that we as health professionals
42

must deal with on a day-by-day basis. (Ex. 1020 at 205.) In 1993, Linnarsson further
explained that potential drug interactions occur in 12% of patients at risk (those
receiving two or more concurrent drugs), and that 1.9% of all drug prescriptions
result in a potential drug interaction. (Ex. 1021 at132.) Still by 1997, Grnroos
lamented that [d]rug interactions may lead to life-threatening injuries. (Ex. 1022 at
13; Ex. 1027 181-83.) As such, it would have been obvious to one of ordinary skill
in the art that during the pre-treatment extensive patient evaluation and complete
physical examination disclosed, for example, in Dishman, information regarding any
other drugs that the patient was taking would have been collected in order to screen
for potential contraindicated drug combinations, as required by Claim 29. (Ex. 1007
at 900; Ex. 1027 184.) See In re Kahn, 441 F.3d 977, 988 (Fed. Cir. 2006) (holding that
the understandings and knowledge of persons having ordinary skill in the art at the
time of the invention [] support the legal conclusion of obviousness.).
With respect to Claim 31, it is important to note that Dishmans regimen is
designed for treating schizophrenics. (Ex. 1007 at 899.) It was well known to
ordinarily skilled artisans that substance abuse is prevalent among schizophrenics. (Ex.
1027 190-92.) For example, Soyka concluded in 1992 that substance abuse is a
very common problem in schizophrenics. (Ex. 1023 at 362.) Similarly, Hamera wrote
in 1995 that [t]he high prevalence of substance use, e.g., alcohol and illegal and
nonprescribed drugs, in schizophrenia is widely recognized. (Ex. 1024 at 559.) Again,
in 1997, Kosten and Ziedords wrote that [m]ost individuals with schizophrenia have
43

problems with abuse of substances ranging from licit substances, such as nicotine, to
illicit ones, such as cocaine, and further explained that [s]everal recent studies have
demonstrated that up to 50 percent of individuals with schizophrenia have either
alcohol or illicit drug dependence, and about 70 percent or more are nicotine
dependent. (Ex. 1025 at 181.) However, Dishman indicates that its clozapine regime
may be contraindicated for those with substance abuse problems. (Ex. 1007 at 900
(The NCCC also recommends that clozapine not be used in patients who, because of
social situation, substance abuse, or other factors, cannot be relied upon to keep
follow-up appointments.) (emphasis added).)
Because the prevalence of substance abuse among schizophrenics was well
known, it would have been obvious to one of ordinary skill in the art at the time of
the 720 Patent that, during the pre-treatment extensive patient evaluation and
complete physical examination disclosed in Dishman, a practitioner should test for
the regimens contraindicated substance abuse by screening for the presence of
alcohol and other drugs. (Ex. 1027 188.) See Par Pharm., Inc. v. TWi Pharms., Inc., 773
F.3d 1186, 1197 (2014) ([T]he motivation to combine does not have to be explicitly
stated in the prior art, and can be supported by testimony of an expert witness
regarding knowledge of a person of skill in the art at the time of invention).
However, as Mitchell teaches, [i]n a survey of self-reports, one must ask
whether the information is valid. (Ex. 1010 at 105.) Indeed, because it was well
known to an ordinarily skilled artisan that, as the National Center on Addiction and
44

Substance Abuse at Columbia University stated in 1994 people are generally reluctant
to admit to alcohol or drug abuse and addiction,3 it would have been obvious to one
of ordinary skill in the art that a substance abuse screen in Dishman should have
comprised testing for evidence of the use of alcohol or other drugs, rather than
solely relying on patient survey information. (Ex. 1026 at 4; Ex. 1027 190, 192.) See
Sciele Pharma, Inc., 684 F.3d at 1259 (Fed. Cir. 2012) (The obviousness analysis entails
an expansive and flexible approach.There need not be precise teachings directed
to the specific subject matter of the challenged claim, for a court can take account of
the inferences and creative steps that a POSA would employ.) (quoting KSR, 550
U.S. at 418). Thus, Claim 31s limitations would have been obvious to one of
ordinary skill in the art at the time of the 720 Patent. (Ex. 1027 180-92.)
Similarly, in a 1993 study, Welte and Russell explained that [s]ocially desirable
responding is the reluctance to admit unpopular beliefs or behavior in order to avoid

making a negative impression. It poses a problem for researchers who rely on selfreport of heavy drinking and drug use. It was concluded that social desirability
response bias probably results in underestimates of rates of heavy drinking and drug
use (Ex. 1032 at 758.)
45

9.
Claim chart for Ground 1 showing exemplary citations in Mitchell,
Dishman , and Cunningham
Element
1pre. In a method for
delivering a drug to a
patient in need of the
drug, while avoiding
the occurrence of an
adverse side effect
known or suspected
of being caused by
said drug, wherein
said method is of the
type
in which prescriptions
for said drug are filled
only after a computer
readable storage
medium has been
consulted to assure
that the prescriber is
registered in said
medium and qualified
to prescribe said drug,
that the pharmacy is
registered in said
medium and qualified
to fill the prescription
for said drug, and the
patient is registered in
said medium and
approved to receive
said drug, the
improvement
comprising:
a. defining a plurality
of patient risk groups
based upon a
predefined set of risk
parameters for said
Prior Art
Mitchell teaches method for delivering teratogenic drug
(isotretinoin) while avoiding exposure of foetus to the drug:
Ex. 1010 at 101 (As an alternative to removing the drug
from the market or formally restricting its use, the
manufacturer proposed an aggressive program designed to
reduce the risk of pregnancy among women taking the drug.
The committee recommended that the major components of
this program be implemented, and the manufacturers
Pregnancy Prevention Program commenced in the fall of
1988. The program was targeted at both prescribers and
patients.).
Dishman teaches computerized program for registering
prescribers and patients:
Ex. 1007 at 899 (The manufacturer, Sandoz, requires all
prescribers and patients to be registered with the Clozaril
National Registry.);
Id. at Abstract (A program in which pharmacists have an
active role in prescribing and dispensing psychoactive
drugs.);
Id. at 899 (Some pharmacists in our institution have
specialized training in psychiatry and have acquired clinical
privileges that allow them to prescribe psychotropic
medications and order laboratory tests.);
Id. at 900 (The VA Central Office established a National
Clozapine Coordinating Center (NCCC). . . . The NCCC
requires that each hospital have a computerized clozapine
prescription lockout system [that] ties the hospitals
laboratory database to the outpatient pharmacy dispensing
software.).
Mitchell teaches a patient-qualification checklist for assigning
patients to the risk groups to which a drug with teratogenic
side effects, such as isotretinoin, can and cannot be
administered:
46

drug;
b. defining a set of
information to be
obtained from said
patient, which
information is
probative of the risk
that said adverse side
effect is likely to
occur if said drug is
taken by said patient;
c. in response to said
information set,
assigning said patient
to at least one of said
risk groups and
entering said risk
group assignment in
said medium;
Ex. 1010 at 102 (The subjects were women of childbearing

age (12 to 59 years of age) who were being treated with
isotretinoin.);
Id. at 105 (The program sought to exclude from isotretinoin
treatment women who were at high risk of becoming
pregnant.).
Mitchell teaches obtaining information from the patient which
is probative of the risk of the adverse side effect:
isotretinoin.);
pregnant.).
Mitchell teaches a patient-qualification checklist for assigning
patients to the risk groups to which a drug with teratogenic
side effects, such as isotretinoin, can and cannot be
administered:
isotretinoin.);
pregnant.);
Id. at 102 ([T]he program also included survey-enrollment
consent forms; physicians were asked to encourage women to
use these forms to enroll at the time isotretinoin was
prescribed.).
Dishman teaches computerized program for patient risk group
assignment based on white blood cell counts:
National Registry, which requires weekly monitoring of each
patients white blood cell (WBC) count and limits medication
dispensing to a one-week supply. The registry permits
community and hospital pharmacies to dispense clozapine
47

only upon the pharmacists verification that the WBC count
is within acceptable limits.);
Id. at 900 (After a patient has been determined eligible for
clozapine therapy, the pharmacist forwards all pertinent
information to the NCCC. After NCCC approval, the
pharmacist enrolls the patient into the hospitals clozapine
tracking system, and clozapine therapy is begun.);
d. based upon said

information and said
risk group
assignment,
determining whether
the risk that said
adverse side effect is
likely to occur is
acceptable; and
e. upon a
determination that
said risk is acceptable,
generating a
prescription approval
code to be retrieved
by said pharmacy
before said
prescription is filled.
Id. (NCCC requires that each hospital have a computerized

clozapine prescription lockout system[that] ties the
hospitals laboratory database to the outpatient pharmacy
dispensing software.).
Mitchell discloses that a determination is made regarding the
acceptability of the risk of prescribing the drug:
isotretinoin.);
pregnant.);
consent forms; physicians were asked to encourage women to
use these forms to enroll at the time isotretinoin was
prescribed.).
Ex. 1027, Fudin Decl. 94.
Dishman discloses approval of acceptable risk through a
registry:
Ex. 1007 at 899900 ([R]egistry [that] permits community
and hospital pharmacies to dispense clozapine only upon the
pharmacists verification that the WBC count is within
acceptable limits. [T]he lockout system prevents the filling
of any clozapine prescription if the computer notices three
consecutive drops in WBC count.).
Cunningham discloses an approval code lockout system for a
pharmacy:
Ex. 1008 at 11:68, 1723 (If authenticity is not established,
it follows that the participating pharmacy cannot dispense
corresponding pharmaceutical product. However, if
48

authenticity is established then the pharmac[ys] terminal dials
the central computing station and data and information from
the pharmac[ys] authorization media and personal
identification is uploaded to the database of the central
computing station 12. Assuming full validation, the central
computing station issues a pharmacy approval code and the
pharmacy records that approval code on the actual presented
product trial media 18. Once validation is established the
pharmacy then dispenses pharmaceutical trial product.).
2. The method of
claim 1 wherein, in
response to said risk
group assignment,
said patient is
counseled as to the
risks of taking said
drug and advised as
to
risk avoidance
measures.
See Ex. 1027, Fudin Decl. 95-98.

Mitchell teaches appropriate counseling for patients regarding
the risks of taking thalidomide and the risk avoidance
measures:
Ex. 1010 at 101 (The materials included guidelines for
patients (instructing them, for example, to warn patients of
risks, obtain negative pregnancy tests, and delay therapy until
the second or third day of the next normal menstrual period.)
They also included a patient-qualification checklist, an
information brochure for patients, contraceptive information,
information about and the necessary forms for a
contraception referral program (in which the manufacturer
would reimburse patients for a visit to another physician for
contraceptive counseling), and a consent form.);
Id. at 105 ([P]rogram encourages communication between
physicians and patients regarding the drugs teratogenic risk
and the need to prevent pregnancy.);
3. The method of
claim 2 wherein said
counseling comprises
full disclosure of said
risks.
Id. at 101 ([T]he manufacturer replaced traditional

medication bottles with a 10-capsule blister pack that
contained information directed specifically at women: the
package included warnings about the risks of becoming
pregnant while taking isotretinoin or during the month after
treatment, an avoid pregnancy icon behind each capsule,
and line drawings of malformations associated with
isotretinoin.).
Mitchell teaches contraceptive counseling comprising full
disclosure of the risks:
49

Id. at 105 ([P]rogram encourages communication between
physicians and patients regarding the drugs teratogenic risk
and the need to prevent pregnancy.);
4. The method of
prescription is filled
only following said
full disclosure and
informed consent of
said patient.
Id. at 101 ([T]he manufacturer replaced traditional

medication bottles with a 10-capsule blister pack that
contained information directed specifically at women: the
package included warnings about the risks of becoming
pregnant while taking isotretinoin or during the month after
treatment, an avoid pregnancy icon behind each capsule,
and line drawings of malformations associated with
isotretinoin.).
Mitchell teaches isotrenoin is prescribed only after full
disclosure of risks is given and informed consent is obtained:
Id. at 102 (of the need for patient consent.);
consent forms.).
Ex. 1027, Fudin Decl. 105.
Mitchell teaches that the prescriber screens patient risk group
assignment and informed consent:
5. The method of
risk group assignment Ex. 1010 at 102 (The enrollment forms were screened on
and said informed
receipt to exclude enrollments that were apparently
50

consent is verified by
said prescriber at the
time that said patient
is registered in said
computer readable
storage medium.
6. The method of
risk group assignment
and said informed
consent is transmitted
to said computer
readable storage
medium by facsimile
and interpreted by
optical character
recognition software.
7. The method of
set of information
includes the results of
diagnostic testing.
8. The method of
fraudulent, men, and previously enrolled women [and] the

eligible women were assigned, at random, to be followed by
one of the two methods.).
Dishman also teaches screening patients file:
Ex. 1007 at 900 ([T]he pharmacist screens potential
candidates before they undergo extensive evaluation. The
screening involves reviewing the patients case with the
requesting practitioner, reviewing the patients file, and
interviewing the patient to ensure that the patient and family
members are committed to weekly blood tests and follow-up.
This screening ensures that the physician does not waste time
evaluating patients who are ineligible for clozapine therapy.
After a patient has been determined eligible for clozapine
therapy, the pharmacist forwards all pertinent information to
the NCCC. After NCCC approval, the pharmacist enrolls the
patient into the hospitals clozapine tracking system, and
clozapine therapy is begun.).
Ex. 1027, Fudin Decl. 106-10.
Dishman teaches transmitting patients risk group assignment
and informed consent to the NCCC database:
See, supra Claim 1(c);
Ex. 1007 at 901 (After each weekly follow-up appointment,
the pharmacist faxes a tracking sheet containing an evaluation
of the patient to the NCCC.).
Ex. 1027, Fudin Decl. 111-15.
Mitchell teaches obtaining negative pregnancy tests before the

treatment:
Ex. 1010 at 101 ([T]he package included [birth]
malformations associated with isotretinoin.);
Id. at 103 ([A] new medication package included warnings
about the need to have a negative blood pregnancy test
before starting therapy.).
Ex. 1027, Fudin Decl. 116-20.
Dishman disclose extensive diagnostic testing, including
51

diagnostic testing is
probative of the onset
of said adverse side
effect.
9. The method of
diagnostic testing is
probative of the
concentration of said
drug in a tissue of
said patient.
10. The method of
diagnostic testing
comprises genetic
testing.
11. The method of
side effect is likely to
arise in said patient.
12. The method of
arise in a foetus
carried by said
patient.
13. The method of
arise in a recipient or
a foetus carried by a
recipient of the bodily
fluid of
said patient.
14. The method of
recipient is a sexual
testing probative of the adverse side effect:

Ex. 1007 at 900 (The NCCC guidelines require extensive
patient evaluation and documentation. A complete
physical examination, including laboratory testing and
electrocardiographic analysis, is required.
Ex. 1027, Fudin Decl. 121-23.
Ex. 1027, Fudin Decl. 124-27.
Ex. 1027, Fudin Decl. 128, 131-34.
Mitchell teaches teratogenic effect of isotretinoin in a foetus:

Ex. 1007 at 101 (Isotretinoin is teratogenic.);
Id. ([I]sotretinoin might be teratogenic in humans.);
Id. at 104 ([U]nderstanding of the teratogenic risks of
isotretinoin and of the need to avoid pregnancy was virtually
universal.).
Mitchell teaches teratogenic effect of isotretinoin in a foetus:
universal.).
Ex. 1027, Fudin Decl. 135-38.
Ex. 1027, Fudin Decl. 135-38.
52

partner of said
patient.
15. The method of
claim 1 further
comprising:
f. defining for each
said risk group a
second set of
information to be
collected from said
patient on a periodic
basis;
See Claim 1pre.

Mitchell teaches collecting information from the patient
periodically:
Ex. 1010 at 101 (Telephone interviews were conducted at
the start of therapy, in the middle of it, and 6 months after it
ended; mailed questionnaires were completed 6 months after
therapy ended.);
Id. at 102 (Each week, 100 women were randomly assigned
to the group interviewed by telephone. They were contacted
three times: at the start of therapy (within one month after
enrollment), when we inquired about the patients
understanding of the hazards of isotretinoin and compliance
with the program; in the middle of therapy (between two and
four months after the start of the isotretinoin), when we
inquired about continued understanding of the hazards of
isotretinoin and compliance with the program; and six
months after the completion of therapy, when we asked
about the occurrence of pregnancy during or after
treatment.);
Id. (Women not randomly assigned to the telephone group
were sent a brief questionnaire six months after starting
isotretinoin to determine the date on which they had
completed or were expected to complete therapy. They were
then mailed a questionnaire six months after that date, which
included the same questions as the third telephone
interview.);
Id. (To minimize memory loss and biased recall, we collected
information on the behavior of physicians and patients at the
start of therapy as well as during treatment.).
Dishman also teaches collecting WBC count information
from the patient on weekly basis:
53

dispensing to a one-week supply.);
Id. at 900 (The screening involves interviewing the
patient to ensure that the patient and family members are
committed to weekly blood tests and follow-up.);
g. obtaining said
second set of
information from said
patient; and
h. entering said
second set of
information in said
medium before said
patient is approved to
receive said drug.
Id. at 901 (After each weekly follow-up appointment, the

pharmacist faxes a tracking sheet containing an evaluation of
the patient to the NCCC.).
See supra Claim 15(f).
Dishman discloses entering patient information in the

computer storage medium prior to treatment:
Ex. 1007 at 900 (Physicians at the NCCC review each
clozapine candidates file before granting approval for use
and review weekly tracking sheets that report patient status.
[T]he pharmacist ensures that the psychiatry resident
orders the necessary laboratory tests, performs the required
clinical evaluation, and documents the results in a weekly
tracking sheet, which the pharmacist forwards to the
NCCC.);
Id. (will allow clozapine prescriptions to be processed only
when WBC counts are within the defined limits);
16. The method of

second set of
information
comprises a survey
regarding said
patients behavior and
compliance with said
risk avoidance
measures.
Id. at 901 (After each weekly follow-up appointment, the

pharmacist faxes a tracking sheet containing an evaluation of
the patient to the NCCC and places the original document in
the patients medical record.).
Mitchell teaches periodic survey to assess compliance with the
risk avoidance measures:
therapy ended.);
Id. at 101-02 (We designed and conducted a survey to assess
the compliance of physicians and patients with the program
and to identify the rate of pregnancy during treatment with
54

isotretinoin and during the month after treatment.);
Id. at 103 (Early in 1992, the questionnaire was modified to
allow more complete information to be obtained regarding
sexual activity and birth control.).
17. The method of

survey is conducted
telephonically using
an integrated voice
response system.
Id. at 104 (Among women enrolled in this survey,

understanding of the teratogenic risks of isotretinoin and of
the need to avoid pregnancy was virtually universal.
Compliance with other aspects of the program was less
complete, although in no case did compliance for any
measure decline during the study period.).
Mitchell teaches periodic survey is conducted telephonically:
therapy ended.);
Id. at 102 (Each week, 100 women were randomly assigned
to the group interviewed by telephone. They were contacted
three times: at the start of therapy (within one month after
enrollment), when we inquired about the patients
understanding of the hazards of isotretinoin and compliance
with the program; in the middle of therapy (between two and
four months after the start of the isotretinoin), when we
inquired about continued understanding of the hazards of
isotretinoin and compliance with the program; and six
months after the completion of therapy, when we asked
about the occurrence of pregnancy during or after
treatment.);
Id. at 103 (As of June 30, 1994, 124,216 women had
completed final telephone interviews.).
18. The method of

patient is a female of
childbearing potential
and said second set of
information
comprises the results
of a pregnancy test.
Ex. 1027, Fudin Decl. 158-61.

Mitchell discloses pregnancy testing in patients:
physicians (instructing them, for example, to warn patients of
the second or third day of the next normal menstrual period).
We designed and conducted a survey to assess the
compliance of physicians and patients with the program
[Pregnancy Prevention Program] and to identify the rate of
55

pregnancy during treatment with isotretinoin and during the
month after treatment.).
Dishman discloses weekly WBC tests:
dispensing to a one-week supply.).
19. The method of
periodic interval
comprises about 28
days.
20. The method of

claim 1 further
comprising providing
said patient with a
contraceptive device
or formulation.
Ex. 1027, Fudin Decl. 162, 169.

Dishman discloses weekly WBC tests:
Ex. 1027, Fudin Decl. 162, 165-70.
Mitchell discloses providing contraceptive counseling to
patients:
Ex. 1010 at 101 (Pregnancy-Prevention Program in Women
of Childbearing Age Receiving Isotretinoin.);
Id. (The materials included an information brochure for
patients, contraceptive information, information about and
the necessary forms for a contraception referral program (in
which the manufacturer would reimburse patients for a visit
to another physician for contraceptive counseling).);
Id. ([T]he manufacturer proposed an aggressive program
designed to reduce the risk of pregnancy among women
taking the drug. The committee recommended that the major
components of this program be implemented, and the
manufacturers Pregnancy Prevention Program commenced
in the fall of 1988.);
Id. (The concern about human teratogenicity proved well
founded. reports of pregnancies in exposed women
continued to accumulate, and by 1989 approximately 78
malformed infants had been reported.);
Id. at 103 ([T]he package included warnings about the risks
of becoming pregnant while taking isotretinoin or during the
56

month after treatment, an avoid pregnancy icon behind each
capsule, and line drawings of malformations associated with
isotretinoin.).
21. The method of
adverse side effect
comprises a
teratogenic effect.
22. The method of

drug is thalidomide.
Ex. 1027, Fudin Decl. 140-45.

Mitchell teaches teratogenic effect of isotretinoin:
universal.).
Ex. 1027, Fudin Decl. 130, 135-39.
Mitchell teaches that the isotretinoin program can serve as a
basis for the use of other teratogenic drugs, including
thalidomide:
Ex. 1010 at 105 (The isotretinoin program offers a novel
approach that seeks to keep the drug available while
minimizing the teratogenic hazard.);
Id. (Thalidomide appears to be an effective treatment for
various medical conditions prompting interest in making
these teratogenic drugs more widely available. The experience
gained with isotretinoin can serve as a basis for considering
how such drugs should be used and monitored, with a view
to ensuring that pregnancies and malformations are reduced
to an absolute minimum.).
23. The method of

teratogenic effect is
likely to arise in a
foetus carried by said
patient.
24. The method of

teratogenic effect is
Ex. 1027, Fudin Decl. 130, 134, 138-39.

Mitchell teaches teratogenic effect of isotretinoinis likely to
arise in a fetus:
universal.).
Ex. 1027, Fudin Decl. 130, 134, 138-39.
57

likely to arise in a
foetus carried by a
fluid of said patient.
25. The method of
fluid of said patient is
a sexual partner of
said patient.
26. The method of
set of information
a pregnancy test.

universal.).
Ex. 1027, Fudin Decl. 130, 135-39.
Ex. 1027, Fudin Decl. 130, 135-39.
Mitchell teaches obtaining negative pregnancy test results

before the treatment:
the second or third day of the next normal menstrual
period).);
Id. at 102 (78 percent [of women] were told to wait for
pregnancy-test results before starting isotretinoin.);
27. The method of

prescription is filled
for no more than
about 28 days.
Ex. 1027, Fudin Decl. 163-64.

Dishman discloses weekly supply of medication:
Ex. 1027, Fudin Decl. 163, 170.
See, supra Claim 1pre and (a)-(e).
28pre and (a)-(e).

28. wherein said
adverse side effect is Ex. 1010 at 101 (Isotretinoin is teratogenic.);
likely to arise in
patients who take said Id. ([I]sotretinoin might be teratogenic in humans.).
drug in combination Dishman teaches agranulocytosis:
58

with at least one other Ex. 1007 at 899 (Patients are monitored for agranulocytosis
drug.
.).
29. The method of
claim 28, wherein said
set of information is
also probative of the
likelihood that said
patient may take said
drug and said other
drug in combination.
30. The method of
set of information
diagnostic testing.
See Ex. 1027, Fudin Decl. 172, 174-75.

Dishman discloses guidelines for extensive patient evaluation:
electrocardiographic analysis, is required.).
Ex. 1027, Fudin Decl. 172, 176-84.
Mitchell teaches obtaining negative pregnancy test results
before isotrenoin treatment:
the second or third day of the next normal menstrual
period).);
Id. at 102 (78 percent [of women] were told to wait for
pregnancy-test results before starting isotretinoin.);
Dishman discloses information containing diagnostic test
results:
Ex. 1027, Fudin Decl. 172, 176-79.

31. The method claim Dishman discloses extensive patient evaluation and teaches
30 wherein said
that its clozapine regime may be contraindicated for those
with substance abuse problems:
diagnostic testing
comprises testing for Ex. 1007 at 900 (The NCCC also recommends that
evidence of the use of clozapine not be used in patients who, because of social
said other drug.
situation, substance abuse, or other factors, cannot be relied
upon to keep follow-up appointments.).
59

Id. (The NCCC guidelines require extensive patient
evaluation and documentation. A complete physical
examination, including laboratory testing and
32. The method of
diagnostic testing
comprises for
evidence which is
indicative of the onset
of said adverse side
effect.
Ex. 1027, Fudin Decl. 172, 180-92.

Dishman discloses extensive patient evaluation and teaches
that its clozapine regime may be contraindicated for those
with substance abuse problems:
Ex. 1007 at 900 (The NCCC also recommends that
clozapine not be used in patients who, because of social
situation, substance abuse, or other factors, cannot be relied
upon to keep follow-up appointments.).
Id. (The NCCC guidelines require extensive patient
evaluation and documentation. A complete physical
examination, including laboratory testing and
Ex. 1027, Fudin Decl. 172, 176-79.
VII. CONCLUSION
Thus, Petitioners respectfully request inter partes review of Claims 132 of U.S.
Patent No. 6,315,720.
Respectfully Submitted,
/Sarah E. Spires/
Sarah E. Spires (Reg. No. 61,501)
SKIERMONT PUCKETT LLP
2200 Ross Ave. Ste. 4800W
Dallas, Texas 75201
P: 214-978-6600/F: 214-978-6601
Lead Counsel for Petitioner
April 23, 2015

Ki O (Reg. No. 68,952)
Dr. Parvathi Kota (Reg. No. 65,122)
Paul J. Skiermont (pro hac vice requested)
SKIERMONT PUCKETT LLP
2200 Ross Ave. Ste. 4800W
Dallas, Texas 75201
P: 214-978-6600/F: 214-978-6621
Back-Up Counsel for Petitioner
60

CERTIFICATE OF SERVICE
I hereby certify that on April 23, 2015, a copy of this Petition for Inter Partes
Review of U.S. Patent No. 6,315,720, including all exhibits, was served via FedEx,
overnight delivery, upon the following:
Celgene Corporation
86 Morris Avenue
Summit, New Jersey 07901
S. Maurice Valla
BakerHostetler
Cira Centre, 12th Floor
2929 Arch Street
Philadelphia, Pennsylvania 19104-2891
Date: April 23, 2015
/Sarah E. Spires/

Ipr2015 01103

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Ipr2015 01103

Uploaded by

Copyright:

Available Formats

Paper No.

Patent No. 6,315,720

GROUNDS FOR STANDING (37 C.F.R. 42.104(a)) ..................................... 1

MANDATORY NOTICES (37 C.F.R. 42.8)..................................................... 1

A. Real Parties-in-Interest (37 C.F.R. 42.8(b)(1)) .................................................... 1

Related Judicial and Administrative Matters (37 C.F.R. 42.8(b)(2)) ................. 2

Lead and Back-Up Counsel (37 C.F.R. 42.8(b)(3)) and Service

PAYMENT OF FEES (37 C.F.R. 42.15(a) and 42.103) ................................ 3

IDENTIFICATION OF CHALLENGE ............................................................. 3

The 720 Patent Specification ............................................................................. 4

The 720 Claims .................................................................................................... 5

The 720 Prosecution History ............................................................................. 6

Claim Construction of Challenged Claims ............................................................. 9

Teratogenic effect ........................................................................................... 10

Adverse side effect ......................................................................................... 11

Statement of Precise Relief Requested for Each Claim Challenged ................. 11

Claims for Which Review is Requested ........................................................... 11

Statutory Grounds of Challenge ....................................................................... 11

D. Overview of the State of the Art and Motivation to Combine ......................... 11

Summary of the Petitions Prior Art References ............................................ 14

A. Ground 1: Claims 132 of U.S. Patent No. 6,315,720 are

Patent No. 6,315,720

Claim 1 is obvious over Mitchell in view of Dishman and in

Dependent Claims 26 are obvious over the prior art of

Dependent Claims 710 are obvious over the prior art of

Dependent Claims 1114 and 2025 are obvious over the

Dependent Claim 15 is obvious over the prior art of Ground 1,

Dependent Claims 1617 are obvious over the prior art of

Dependent Claims 1819 and 2627 are obvious over the

The added limitations of independent Claim 28 and dependent

Claim chart for Ground 1 showing exemplary citations in

Patent No. 6,315,720

Patent No. 6,315,720

Patent No. 6,315,720

U.S. Patent No. 6,315,720 to Bruce A. Williams and Joseph K.

U.S. Patent No. 6,315,720 Prosecution History (720 prosecution

U.S. Patent No. 6,063,026 to Mark A. Schauss and Patricia Kane,

Guideline for the clinical use and dispensing of thalidomide, R.J.

Pharmacists role in clozapine therapy at a Veterans Affairs medical

U.S. Patent No. 5,832,449 to David W. Cunningham, filed on Nov.

U.S. Patent No. 6,055,507 to David W. Cunningham, filed on Aug.

A Pregnancy-Prevention Program in Women of Childbearing Age

S.T.E.P.S.TM: A Comprehensive Program for Controlling and

Transcript of the FDAs Forty-Seventh Meeting of the

Patent No. 6,315,720

Transcript of the FDAs Forty-Seventh Meeting of the

CDC Meeting: 03/26/1997 Minutes and Agenda Regarding

Assessing the Effectiveness of a Computerized Pharmacy System,

Review of computer applications in institutional pharmacy1975

Interactive Voice Response Systems in Clinical Research and

Passage of Chemicals into Human and Animal Semen: Mechanisms

Preparing for Thalidomides Comeback, Cori Vanchieri, Annals of

Development of a Computerized Drug Interaction Database

A medication database a tool for detecting drug interactions in

Prevalence of Alcohol and Drug Abuse in Schizophrenic

Alcohol, Cannabis, Nicotine, and Caffeine Use and Symptom

Patent No. 6,315,720

Substance Abuse and Schizophrenia: Editors Introduction,

Substance Abuse and Women on Welfare, Jeffrey C. Menill,

Declaration of Jeffrey Fudin, R.Ph., B.S., Pharm.D., DAAPM, FCCP,

Curriculum Vitae for Jeffrey Fudin, R.Ph., B.S., Pharm.D., DAAPM,

Center for Drug Evaluation and Research Approval Package for

Joint Claim Construction and Prehearing Statement, Celgene Corp. v.