Ipr2015 01102

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

Level of Ordinary Skill in the Art .......................................................................... 17
VI. 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 Powell in view of Dishman and in
i

further view of Cunningham and the knowledge of one of ordinary
skill in the art. ........................................................................................................... 17
1.
Claim 1 is obvious over Powell 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 Powell in view of
Dishman and in further view of the knowledge of one of
ordinary skill in the art. ..................................................................................... 24
3.

4.
Dependent Claims 1114 and 2025 are obvious over the

prior art of Ground 1, and more specifically over Powell in
view of the knowledge of one of ordinary skill in the art. ............................ 30
5.
Dependent Claim 15 is obvious over the prior art of Ground 1,

and more specifically over Powell in view of Dishman and in
further view of the knowledge of one of ordinary skill in the art................ 34
6.

7.
Dependent Claims 1819 and 2627 are obvious over the

prior art of Ground 1, and more specifically over Powell in
view of Dishman and in further view of the knowledge of
one of ordinary skill in the art. ......................................................................... 37
8.
The added limitations of independent Claim 28 and dependent

Claims 2932 are obvious over Powell in view of Dishman and
in further view of Cunningham and knowledge of one of ordinary
skill in the art. ..................................................................................................... 40
9.
Claim chart for Ground 1 showing exemplary citations in Powell,

Dishman, and Cunningham................................................................................... 44
VII. CONCLUSION ........................................................................................................... 60

ii

Cases
TABLE OF AUTHORITIES
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) ....................................................................................... 22
Dow Chem. Co. v. Sumitomo Chem. Co.,
257 F.3d 1364 (Fed. Cir. 2001) ....................................................................................... 17
Dystar Textilfarben GmbH v. C.H. Patrick Co.,
464 F.3d 1356 (Fed. Cir. 2006) ....................................................................................... 24
In re Am. Acad. of Sci. Tech. Ctr.,
367 F.3d 1359 (Fed. Cir. 2004) ....................................................................................... 10
In re Cuozzo Speed Techs., LLC,
778 F.3d 1271 (Fed. Cir. 2015) ......................................................................................... 9
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) ....................................................................................... 18
In re Kahn,
441 F.3d 977 (Fed. Cir. 2006) ......................................................................................... 42
In re Venner,
262 F.2d 91 (C.C.P.A. 1958) ........................................................................................... 37
KSR Int'l Co. v. Teleflex Inc.,
550 U.S. 398 (2007)................................................................................. 23, 24, 34, 37, 39
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 (2014) ................................................................................................. 22, 43
Pentec, Inc. v. Graphic Controls Corp.,
776 F.2d 309 (Fed. Cir. 1985) ......................................................................................... 18
Perfect Web Techs., Inc. v. InfoUSA, Inc.,
587 F.3d 1324 (Fed. Cir. 2009) .................................................................... 27, 32, 35, 41
Pfizer, Inc. v. Apotex, Inc.,
480 F.3d 1348 (Fed. Cir. 2007 ........................................................................................ 20
iii

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) ...........................................................................33, 39, 44
Tyco Healthcare Grp. LP v. Ethicon Endo-Surgery, Inc.,
774 F.3d 968 (Fed. Cir. 2014) ................................................................................... 21, 29
Unigene Labs., Inc. v. Apotex, Inc.,
655 F.3d 1352 (Fed. Cir. 2011) ....................................................................................... 30
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 Divisional)
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)
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. (Id. 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
to risk groups based on the risk that the drug will cause adverse side effects and
4

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, 18:16-42.)
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 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 approval 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 1006, 1007, and
1008
view of Powell (Ex. 1006), 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 also 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 to keep prescription records 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 such as the patients gender, allergies,
height, weight, 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, 18283.) Practitioners
13

then used this data to determine (1) whether to prescribe a drug to a patient, and (2)
the duration of the prescription. (See Ex. 1016 at 53, 6367.)
Thus, in the case of thalidomide or any other 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.1012 at 11112; Ex. 1027 59.)
1.
Summary of the Petitions Prior Art References

a.
Powell (Ex. 1006)
Powell constitutes prior art under 35 U.S.C. 102(b) because it was published in
1994. (Ex. 1006 at 901.) During prosecution of the 720 Patent, the examiner did not
consider this reference. (See Ex. 1001 at Cover.)
Powell discloses a guideline designed to promote the safest possible clinical use
and dispensing of thalidomide. (Ex. 1006 at 901.) In particular, it teaches criteria for
the clinical use of thalidomide, including the exclusion of patients in certain risk
groupssuch as those who are pregnant or wish to become pregnant. (Id. at 901.) It
also recommends obtaining informed consent and continued monitoring of patients
after treatment with the drug has begun. (Id. at 902.)
Powell describes in detail the counseling that should be provided to patients
treated with thalidomide. (See id. at 90104.) For example, Powell teaches that each
patient should be given an information sheet detailing the contraindications,
14

warnings, and precautions associated with the use of the drug. (Id. at 902.) A sample
information sheet is provided in the reference, which includes a paragraph detailing
[d]amage to babies that could result from thalidomide. (Id. at 903, Fig. 1.)
In addition, Powell discloses that the risk subgroup of [w]omen with
childbearing potential must agree to (1) take a pregnancy test within two weeks of
starting treatment to ensure they are not pregnant, (2) take reliable contraceptive
precautions during and for a period after treatment, and (3) stop taking thalidomide
immediately should they miss a period and consult their physician. (Id. at 901902.)
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
approval, each patient underwent extensive evaluation and documentation to identify
15

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 clinical criteria were
metspecifically, when white blood cell counts fell 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,
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
16

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 person 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 5
10 years of experience and a license to practice as a registered pharmacist in any one
or more of the United States. (Ex. 1027 16.) A POSA 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.
(Id.)
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 Powell 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 Powell 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
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
17

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 seeking to treat patients with a drug known or
suspected of causing an adverse side effect as in Claim 1s preamble, would look to
Powell for guidance on the clinical use and dispensing of the drug, 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 preamble requires. (Ex. 1006 at 901; Ex. 1027 79.) 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.).
18

With respect to Claim 1 of the 720 Patent, an ordinarily skilled artisan would
understand from Powell 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). (Ex. 1027 80.)
Specifically, Powell teaches a checklist for assigning patients to the risk groups
to which a drug with teratogenic side effects, such as thalidomide, 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). (See Ex. 1006 at 901; Ex. 1027 81-82.) Powells
risk group list includes, for example, patients unable to understand the potential risk
from the use of thalidomide, unlikely to be able to comply with the prescribing
instructions, and women who wish to become pregnant, with patients outside of
these groups falling into a separate, lower risk category. (Ex. 1006 at 901.) 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
19

information from the patient such as their ability to comply with the prescribing
instructions and wish to become 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. 1006 at 901; Ex. 1027 83.)
With respect to the second portion of Claim 1(c)entering said risk group
assignment in said mediuma POSA would understand from Powell that written
records should be kept relating to risk group and related information. For example,
Powell recommends that such [r]ecords should include the amount of thalidomide that
has been made, the form of the finished product, the named patient, the prescribing
doctor and the person to whom it has been supplied. (Ex. 1006 at 904; Ex. 1027
89.) While Powell does not explicitly mention keeping these records in a computer
readable storage medium, it would have been obvious to an ordinarily skilled artisan
that electronic records of information such as the patient risk group assignment would
be useful and easy to achieve. (Ex. 1027 90.) 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 a prior art
technique] would work for its intended purpose.).
Like Powell, which teaches guidelines for dispensing tightly-controlled
thalidomide, Dishman discloses a program for tightly controlling the dispensing of the
antipsychotic drug clozapine. (See Ex. 1007 at 899901.) Armed with Powells
disclosure, an ordinarily skilled artisan would have been motivated to look to the
20

Dishman system 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 91.) 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 clozapine system described in Dishman when developing a thalidomide
system like that disclosed in Powell. (Ex. 1012 at 11112.) 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 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.) A POSA would have understood from the Dishman reference that this
computerized system must include the patients risk group assignment data in order to
21

determine which prescriptions should be locked out. (Ex. 1027 94.) See Par Pharm.,
Inc., 773 F.3d at 11941195.
Finally, Claim 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 notices three consecutive drops in WBC
count. (Ex. 1007 at 899900; Ex. 1027 99.)
Further, as the 720 Patent 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
required by Claim 1(e)known to ordinarily skilled artisans at the timewould be
obvious for one of ordinary skill in the art to use to implement Dishmans lockout
system. (Ex. 1027 102.) 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
22

technical grasp. If this leads to the anticipated success, it is likely the product not of
innovation but of ordinary skill and common sense.) (quotation omitted).
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
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 103.) See KSR Int'l Co. v.
Teleflex Inc., 550 U.S. 398, 41617 (2007) (where a 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.) (quotations and citations omitted).
In view of the guidelines for the avoidance of treating pregnant patients with
thalidomide taught by Powell, it would have been obvious to a POSA to implement the
methods disclosed in Dishman and Cunningham to limit dispensation of a drug
23

associated with adverse effects to certain risk groups. (Ex. 1027 104.) 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, a POSA treating a patient with a teratogenic or other risk-laden drug in
accordance with the guidelines disclosed in Powell would look to published methods
for limiting dispensation of other drugssuch as the clozapine registry found in
Dishman and the approval code system taught by Cunninghamand would view Claim
1 of the 720 Patent obvious in view of these three references. (Ex. 1027 105.) 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
24

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).)
Powell discloses that [a] doctor prescribing thalidomide on a named patient
basis is entirely responsible for the patients welfare. He must inform the patient of
any contraindications, warnings and precautions associated with the use of the drug.
(Ex. 1006 at 902.) In addition, Powell urges that [e]ach patient being treated with
thalidomide should be given an information sheet counseling that:
Thalidomide is a drug which can have severe side effects.
Damage to babies: This is very important for all women considering
thalidomide. Thalidomide is toxic to the developing baby, especially in
the early months of pregnancy. If you wish to consider thalidomide you
must be prepared to use adequate contraception throughout the duration
of thalidomide therapy and for 3 months after it has finished. Should
contraception fail, any resulting pregnancy may incur damage to the baby
and consequently, if you miss a period at any time during treatment, you
must stop thalidomide immediately and contact the doctor who
prescribed the thalidomide. A pregnancy test would then be arranged
and appropriate counselling given. Should pregnancy be confirmed,
further investigations to assess any damage to the baby would be
indicated. Your doctor can advise you about adequate contraception.
25

(Ex. 1006 at 903.) This information sheet meets the counseling requirements of
Claims 2 and 3. (Ex. 1027 111-12.)
Powell further teaches that [f]ully informed consent should be obtained using a
written consent form and a signed agreement and that [p]atients should be
specifically excluded from treatment from thalidomide if they are either [u]nwilling
to sign a consent form or [u]nable to understand the potential risk from the use of
thalidomide. (Ex. 1006 at 901.) These teachings meet the disclosure and informed
consent treatment prerequisites of Claim 4.
Additionally, because Powell teaches that [a] doctor prescribing thalidomide on
a named patient basis is entirely responsible for the patients welfare, it would have
been obvious to one of ordinary skill in the art that the prescribing doctor should
verify the disclosed requirements for treatmentsuch as the patients informed
consent and risk group assignmentwhen registering the patient in the database to
receive the drug. (Ex. 1006 at 90102; Ex. 1027 116-17.) 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
26

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 118.)
The previous disclosure also renders obvious to an ordinarily skilled artisan that
the informed consent, risk group assignment, and other portions of the patients file
in the Dishman system are transmitted to the NCCC database described above with
respect to Claim 1(c), and as required by the first portion of Claim 6. (Ex. 1027
93-95.) 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 121.) Consequently, it 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 122.) 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
27

flexible obviousness inquiry to include the background knowledge, creativity, and
common sense of the person of ordinary skill.).
3.
Claims 710 depend from Claim 1, adding limitations already 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 Powell and Dishman disclose extensive diagnostic testing, including testing
probative of the onset of said adverse side effect, prior to treatment. Thus, both
Powell and Dishman teach the limitations of Claims 7 and 8. Specifically, Powell teaches
that [p]regnancy should be excluded before instituting therapy with thalidomide,
specifically by a negative pregnancy test within 2 weeks prior to starting therapy since
[t]halidomide is toxic to the developing baby, and that [a]ppropriate clinical and
electrophysiological measurements should be recorded before treatment is
commenced. (Ex. 1006 at 90103.) 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.)
28

With respect to Claim 9, it would have been obvious to an ordinarily skilled
artisan to include, within the extensive diagnostic testing taught by Powell and Dishman,
testing for the drug concentration in patient tissue. (Ex. 1027 130.) Specifically, for a
patient previously 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 131.) 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 131-32.) 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 an ordinarily
skilled artisan to include genetic testing in the extensive diagnostic testing taught by
Powell and Dishman. (Ex. 1027 133.) 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 Powell. (Ex. 1027 134.) Similarly, because there is frequently a genetic
component in schizophreniathe ailment treated in Dishmanone of ordinary skill
in the art would have expected that the extensive diagnostic testing in Dishman would
have included genetic testing. (Ex. 1027 136.) More generally, because genetic
29

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 treatments as those disclosed in Powell
and Dishman. (Ex. 1027 137.) 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 Powell 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
30

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
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.)
Powell explicitly discloses that thalidomides side effects arise in the patient
taking the drugin the case of irreversible peripheral neuropathy, and also in a
fetus carried by the patient taking the drugin the case of teratogenicity, satisfying
Claims 11, 12, 21, 22 and 23. (Ex. 1006 at 901; Ex. 1027 142-43, 148-49.)
By the time that the 720 Patent was filed, it was well known to those of
ordinary skill in the art that certain drugs, likely including thalidomide, could be found
in semen, and thus could be transmitted to a sexual partner of a male undergoing
treatment with the drug. For example, by 1982, Mann and Lutwak-Mann had
discovered that:
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
31

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; Ex. 1027 145-46.) For this reason, it
was obvious to one of ordinary skill in the art that a teratogenic drug, such as
thalidomide discussed in Powell, 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 147-48.) 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 thalidomide had been well known since
the 1960s, as Powell discusses. (Ex. 1006 at 901 (In the 1960s thalidomide virtually
disappeared from clinical use after it was demonstrated that it is both a causative agent
of severe irreversible peripheral neuropathy and a human teratogen.).) 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 thalidomide. (Ex.
1027 150.) This is why Powells [g]uideline for the clinical use and dispensing of
thalidomide taught that [i]f you wish to consider thalidomide you must be prepared
to use adequate contraception throughout the duration of thalidomide therapy and for
32

3 months after it has finished, and further taught that [p]atients should be excluded
from treatment with thalidomide if they are:
Women of childbearing potential:
i. who have not practised a reliable form of contraception for 1 year;
ii. who are unwilling to take reliable contraceptive precautions;
iii. who are considered not capable of complying with the requirements
for reliable contraception. Reliable contraceptive methods include the
contraceptive pill, an intrauterine device, surgical sterilization of patient
or sole partner. Female patients who do not normally practise
contraception because of a history of infertility should do so whilst
taking thalidomide.
(Ex. 1006 at 901 (emphasis added), 903; Ex. 1027 152.) Finally, Powell teaches
informing patients that [y]our doctor can advise you about adequate contraception.
(Ex. 1006 at 903.) In light of Powells teachings, it would have been obvious to one of
ordinary skill in the art that when advising the patient about adequate
contraception, the may provide the patient with a contraceptive device or
formulation as in Claim 20, to accomplish Powells objective of ensuring that
[w]omen of childbearing potential taking thalidomide also take reliable
contraceptive precautions. (Ex. 1027 154.) 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 ordinary skill can implement a predictable variation, 103 likely bars its
patentability) (quotation omitted).
33

5.
Dependent Claim 15 is obvious over the prior art of Ground 1, and

more specifically over Powell 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 Powell 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, Powell discloses that [f]ollow-up visits should be at monthly
intervals or less for the first 3 months to enable the clinician to detect side
effects/early signs of toxicity. (Ex. 1006 at 902.) Powell further discloses that [t]his
treatment is monitored in the out-patients clinic, initially with monthly visits. You will
be asked to have an electric nerve test at regular intervals. (Ex. 1006 at 903.)
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
34

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 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.) 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 163.) 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.)
35

With respect to Claim 16s requirement of a survey regarding said patients
behavior and compliance with said risk avoidance measures, both Powell and Dishman
teach the importance of compliance with their established risk avoidance measures, as
well as pre-treatment interview surveys regarding the patients behavior and ability to
comply with risk avoidance measures. Specifically, Powell teaches that [p]atients
should be specifically excluded from treatment with thalidomide if they are
[u]nlikely to be able to comply with the prescribing instructions or considered not
capable of complying with the requirements for reliable contraception. (Ex. 1006 at
901 (emphasis added).) Dishman teaches interviewing the patient to ensure that the
patient and family members are committed to weekly blood tests and follow-up.
(Ex. 1007 at 900 (emphasis added).) Additionally, Dishman discloses that[t]he 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 that the NCCC required weekly. (Ex. 1007 at 900 (emphasis added).)
Although neither reference explicitly discloses conducting a survey regarding
the patients behavior and compliance on a periodic basis after treatment has begun,
Powell does stress that [f]ollow up visits should be at monthly intervals or less for the
first 3 months [and t]he warnings about the possible toxicity and the need for
adequate contraception should be reinforced. Adequate time should be allowed to
answer all questions raised by the patient. (Ex. 1006 at 902.) In light of the
importance of compliance taught in both Powell and Dishman, when implementing
36

Powells directive to reinforce the toxicity warnings and contraception requirements
taught to the patient prior to treatment, it would have been obvious to one of
ordinary skill in the art to do so by repeating a version of the patient interview surveys
conducted prior to treatment in both Powell and Dishman. (Ex. 1027 170.) See KSR
Intl Co., 550 U.S. at 417. These surveys would meet the requirements of Claim 16.
Further, because one method of conducting surveys well known to those of ordinary
skill in the art at the time of the 720 Patent was via the 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 171; 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 Powell 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, adding limitations 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 pregnancy test comprises
37

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. (Id. at
19:4320:2.)
Powell explicitly discloses that, in light of thalidomides teratogenicity,
[p]regnancy should be excluded before instituting therapy with thalidomide,
specifically by a negative pregnancy test within 2 weeks prior to starting therapy, as
Claim 26 requires. (Ex. 1006 at 901.)
Powell further teaches obtaining mid-treatment pregnancy test results from
patients after thalidomide treatment has begun: Women of childbearing potential
should agree to stop taking thalidomide immediately should they miss a period, and
urgently contact their prescribing physician. A pregnancy test should be provided and,
if positive, appropriate counselling should be given. (Ex. 1006 at 901.) Dishman
similarly teaches that, contraindications to clozapine therapy include pregnancy,
and so it would have been obvious to one of ordinary 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 175-76.)
Although neither reference teaches requiring pregnancy tests before prescribing
the next cycle of drugs, Dishman does teach requiring weekly WBC tests before
prescribing the next week of drugs, as discussed above with respect to Claim 15(h).
38

(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 Powells requirement for excluding pregnancy by a
negative pregnancy test within 2 weeks prior to starting therapy, it would have been
obvious to one of ordinary skill in the art to apply Powells pregnancy test requirement
to Dishmans periodic testing before prescription requirement, satisfying Claim 18.
(Ex. 1006 at 901; Ex. 1027 178.) 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. (Ex. 1027 179.) 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 180.) See Sciele Pharma, Inc., 684
F.3d at 1259. Further, applying Dishmans one-to-one correspondence between
testing intervals 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 181.) See KSR Intl Co., 550 U.S. at 417 ([I]f a
technique has been used to improve one device, and a POSA would recognize that it
39

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 Powell 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 testing comprises testing for evidence of the
use of said other drug and comprises testing for evidence which is indicative of the
onset of said adverse event. (Id. at 20:3242.)
It would have been obvious to an ordinarily skilled artisan that the adverse
effects described in Powell and Dishmanperipheral neuropathy, teratogenicity, and
40

agranulocytosiswould have also arisen in patients who take said drug in
combination with at least one other drug, as Claim 28 requires. (Ex. 1006 at 904;
Ex. 1007 at 899; Ex. 1027 185.) See Perfect Web Techs., Inc., 587 F.3d at 1328.
As discussed with respect to Claims 7 and 8, both Powell and Dishman disclose
extensive diagnostic testing, including testing indicative of the onset of said adverse
side effect, prior to treatment. Thus, both Powell and Dishman teach the limitations of
Claims 30 and 32. Specifically, Powell teaches that [p]regnancy should be excluded
before instituting therapy with thalidomide, specifically by a negative pregnancy test
within 2 weeks prior to starting therapy since [t]halidomide is toxic to the
developing baby, and that [a]ppropriate clinical and electrophysiological
measurements should be recorded before treatment is commenced. (Ex. 1006 at
90103.) Dishman also 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 191.) For example, in 1983, Shinn states that
[d]rug [i]nteractions are a clearly defined problem that we as health professionals
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
41

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.) 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 195.) 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 196.) 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
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
42

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).) (Ex. 1027 196-98.)
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 199.) 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
Substance Abuse at Columbia University stated in 1994 people are generally reluctant
43

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 203.) 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 190-202.)
9.
Claim chart for Ground 1 showing exemplary citations in Powell,

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
3
Prior Art
Powell teaches methods for delivering thalidomide (teratogenic
drug) to patients in need of the drug while avoiding exposure of
the foetus to the drug:
Ex. 1006 at 901 (This guideline is designed to promote the
safest possible clinical use and dispensing of thalidomide. [I]t
cannot be overstated that the risks of teratogenicity.).
Dishman teaches computerized program for registering
Similarly, in 1993, 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 self-report of
heavy drinking and drug use. (Ex. 1032 at 758.)
44

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 drug;
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). Physicians at the
NCCC review each clozapine candidates file before granting
approval for use and review weekly tracking sheets that report
patient status. Each VA medical center is required to establish a
clozapine treatment team, headed by the chief of the psychiatry
service and including representatives from the psychiatry,
pharmacy, laboratory, medicine, and nursing services. The
clozapine treatment team reviews new applications for clozapine
use and provides clinical and demographic information for all
new patients to the NCCC.);
Id. (The NCCC requires that each hospital have a computerized
clozapine prescription lockout system. The lockout system ties
the hospitals laboratory database to the outpatient pharmacy
dispensing software.).
Powell teaches a checklist for assigning patients to the risk groups

to which a drug with teratogenic side effects, such as
thalidomide, can and cannot be administered:
Ex. 1006 at 901 ([T]he risks of teratogenicity and peripheral
neuropathy must be recognized, and addressed in each and every
patient.);
45

Id. (Patients should be specifically excluded from treatment
with thalidomide for any of the following reasons: a. Unwilling
to sign a consent form. b. Unable to understand the potential
risk from the use of thalidomide. c. Unlikely to be able to comply
with the prescribing instructions. d. Women who wish to
become pregnant. e. Women of childbearing potential.).
b. defining a set of Powell teaches obtaining information from the patient which is of
information to be the risk that the adverse side effect is likely to occur in the
obtained from said patient:
patient, which
information is
probative of the
patient.);
risk that said
adverse side effect Id. (Patients should be specifically excluded from treatment
is likely to occur if with thalidomide for any of the following reasons: a. Unwilling
said drug is taken to sign a consent form. b. Unable to understand the potential
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;
Powell teaches written records of the prescribers, pharmacies, and

patients:
Ex. 1006 at 904 (Records should include the amount of
thalidomide that has been made, the form of the finished
product, the named patient, the prescribing doctor and the
person to whom it has been supplied.);
Id. ([T]he order [for thalidomide] should be made in writing
with the name of the patient, the prescribing doctor and the
hospital address and telephone number. The letter should
include a statement that the doctor is familiar with the use of
thalidomide and its side effects, including peripheral neuropathy
and teratogenicity. Also, a written assurance should be obtained
that the drug will only be dispensed by the hospital pharmacist to
the named patient in accordance with the prescription.).
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
46

dispensing to a one-week supply. The registry permits
community and hospital pharmacies to dispense clozapine only
upon the pharmacists verification that the WBC count is within
acceptable limits.);
Id. at 900 (As a member of the clozapine treatment team, 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. After the physician completes the evaluation,
the pharmacist reviews the documentation with the rest of the
clozapine treatment team. 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.);
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.).
d. based upon said Powell discloses that a determination is made regarding the
information and
acceptability of the risk of prescribing the drug:
said risk group
Ex. 1006 at 901 ([I]t cannot be overstated that the risks of
assignment,
teratogenicity and peripheral neuropathy must be recognized,
determining
and addressed in each and every patient.);
whether the risk
that said adverse
side effect is likely with thalidomide for any of the following reasons: a. Unwilling
to sign a consent form. b. Unable to understand the potential
to occur is
acceptable; and
e. upon a
determination that
said risk is
acceptable,
generating a
prescription
See Ex. 1027, Fudin Decl. 96-98.

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
47

approval code to
be retrieved by
said pharmacy
before said
prescription is
filled.
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
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.).
See Ex. 1027, Fudin Decl. 99-103.

2. The method of Powell teaches appropriate counseling for patients regarding the
claim 1 wherein, in risks of taking thalidomide and the risk avoidance measures:
response to said
Ex.1006 at 902 (A doctor prescribing thalidomide on a named
risk group
patient basis is entirely responsible for the patients welfare. He
assignment, said
must inform the patient of any contraindications, warnings and
patient is
precautions associated with the use of the drug.);
counseled as to
the risks of taking Id. at 903, Figure 1 (PATIENT INFORMATION SHEET
FOR THALIDOMIDE USE Thalidomide is toxic to the
said drug and
developing baby, especially in the early months of pregnancy. If
advised as to
you wish to consider thalidomide you must be prepared to use
risk avoidance
adequate contraception throughout the duration of thalidomide
measures.
therapy and for 3 months after it has finished.).
3. The method of
claim 2 wherein
said counseling
comprises full
disclosure of said
risks.
Powell teaches counseling comprising full disclosure of risks of

thalidomide:
Ex.1006 at 901 (A pregnancy test should be provided and, if
positive, appropriate counselling should be given.);
Id. (Fully informed consent should be obtained using a written
consent form and a signed agreement.);
Id. at 902 (Each patient being treated with thalidomide should
be given an information sheet (Figure 1). A doctor prescribing
48

thalidomide must inform the patient of any contraindications,
warnings and precautions associated with the use of the drug.
A sample patient information sheet is provided, which contains
information relating to its proposed use and warnings about the
potential, severe side effects of thalidomide. It should be
updated as required.);
4. The method of
claim 3 wherein
said prescription is
filled only
following said full
disclosure and
informed consent
of said patient.
Id. at 903, Figure 1 (PATIENT INFORMATION SHEET

FOR THALIDOMIDE USE Thalidomide is a drug which
can have severe side effects. This means it can only be used to
treat a few debilitating conditions in which alternative treatments
have been tried and failed. Thalidomide must be used with great
care by patients and doctors and treatment will involve careful
monitoring. Morning drowsiness is the most noticeable problem.
Drowsiness may impair your ability to drive and operate
machinery. Nerve damage: Pins and needles of hands and feet are
early signs of nerve damage and can develop after repeated
courses or regular administration of thalidomide. Damage to
babies: This is very important for all women considering
thalidomide. Thalidomide is toxic to the developing baby,
especially in the early months of pregnancy. This treatment
involves you in possible risks and benefits. You should not agree
to start thalidomide until you clearly understand these.).
Powell teaches that thalidomide is prescribed only after full
disclosure of risks is given and informed consent is obtained:
Ex.1006 at 901 (Fully informed consent should be obtained
using a written consent form and a signed agreement.);
Id. at 901-02 (A pregnancy test should be provided and, if
positive, appropriate counselling should be given.);
Id. at 901 (Patients should be specifically excluded from
treatment with thalidomide for any of the following reasons: a.
Unwilling to sign a consent form. b. Unable to understand the
potential risk from the use of thalidomide.);
Id. at 902 (Each patient being treated with thalidomide should
be given an information sheet (Figure 1). A doctor prescribing
thalidomide on a named patient basis is entirely responsible for
the patients welfare. He must inform the patient of any
contraindications, warnings and precautions associated with the
use of the drug.);
49

Id. at 903, Figure 1 (PATIENT INFORMATION SHEET
FOR THALIDOMIDE USE This treatment involves you in
possible risks and benefits. You should not agree to start
thalidomide until you clearly understand these.).
5. The method of
claim 4 wherein
said risk group
assignment and
said informed
consent is verified
by said prescriber
at the time that
said patient is
registered in said
computer readable
storage medium.
6. The method of
claim 5 wherein
said 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
claim 1 wherein
said set of
information
includes the
Ex. 1027, Fudin Decl. 113-14.

Dishman teaches that the pharmacist screens patients file before
the treatment:
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.
After the physician completes the evaluation, the pharmacist
reviews the documentation with the rest of the clozapine
treatment team. 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.).
Dishman teaches faxing patients evaluation to the NCC:
Ex. 1007 at 901 (Once the pharmacist and psychiatrist have
selected a drug regimen for treating the adverse effects, the
pharmacist makes routine dosage adjustments. 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.);
Id. (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. 1027, Fudin Decl. 120-23.
Powell teaches that the set of information includes the results of
diagnostic testing:
Ex. 1006 at 901 (Pregnancy should be excluded before
instituting therapy with thalidomide, specifically by a negative
pregnancy test within 2 weeks prior to starting therapy.);
50

results of
diagnostic testing.
Id. at 902 (Appropriate clinical and electrophysiological

measurements should be recorded before treatment is
commenced. For certain conditions, photographs may be useful
to monitor the progress of treatment.).
Dishman discloses extensive patient evaluation:
8. The method of
claim 7 wherein
said diagnostic
testing is probative
of the onset of
said adverse side
effect.
Ex. 1007 at 900 ([T]he VA developed its own clozapine

monitoring program and received approval from Sandoz to
dispense clozapine. The NCCC guidelines require extensive
patient evaluation and documentation. A complete physical
examination, including laboratory testing and
electrocardiographic analysis, is required.).
Powell teaches diagnostic testing for adverse side effect:
9. The method of
claim 7 wherein
said diagnostic
testing is probative
of the
concentration of
said drug in a
tissue of said
patient.

Powell teaches diagnostic testing to measure concentration of
drug in a patient:
Ex. 1006 at 902 (Appropriate clinical and electrophysiological
51

Ex. 1027, Fudin Decl. 129-32.
10. The method of Ex. 1027, Fudin Decl. 133-37.
claim 7 wherein
said diagnostic
testing comprises
genetic testing.
11. The method of Powell discloses thalidomide side effects in the patient:
claim 1 wherein
Ex. 1006 at 901 ([T]halidomide is both a causative agent of
said side effect is
severe irreversible peripheral neuropathy and a human
likely to arise in
teratogen.);
said patient.
Id. ([T]he risks of teratogenicity and peripheral neuropathy must
be recognized, and addressed in each and every patient.).
12. The method of Powell discloses thalidomide side effects in a foetus:
claim 1 wherein
said side effect is
likely to arise in a teratogen.);
foetus carried by
said patient.
be recognized, and addressed in each and every patient.);
with thalidomide for any of the following reasons d. Women
who wish to become pregnant. e. Women of childbearing
potential.).
13. The method of Powell discloses thalidomide side effects in a recipient or a foetus
claim 1 wherein
carried by a recipient of the bodily fluid of
said side effect is
said patient:
likely to arise in a
recipient or a
foetus carried by a severe irreversible peripheral neuropathy and a human
teratogen.);
recipient of the
bodily fluid of
said patient.
be recognized, and addressed in each and every patient.);
Id. (If you wish to consider thalidomide you must be prepared
to use adequate contraception throughout the duration of
thalidomide therapy and for 3 months after it has finished.);
52

potential: Women of childbearing potential: i. who have not
practised a reliable form of contraception for 1 year; ii. who are
unwilling to take reliable contraceptive precautions; iii. who are
considered not capable of complying with the requirements for
reliable contraception. Reliable contraceptive methods include
the contraceptive pill, an intrauterine device, surgical sterilization
of patient or sole partner. Female patients who do not normally
practise contraception because of a history of infertility should
do so whilst taking thalidomide.);
Id. at 903 (Your doctor can advise you about adequate
contraception.).
Ex. 1027, Fudin Decl. 144-47.
14. The method of Ex. 1027, Fudin Decl. 144-47.
claim 13 wherein
said recipient is a
sexual partner of
said patient.
15. The method of See Claim 1pre.
claim 1 further
comprising:
f. defining for
Powell discloses periodic monitoring and evaluation of patients:
each said risk
Ex. 1006 at 902 (Follow-up visits should be at monthly intervals
group a second set or less for the first 3 months to enable the clinician to detect side
of information to effects/early signs of toxicity.);
be collected from
Id. at 903 (This treatment is monitored in the out-patients clinic,
said patient on a
initially with monthly visits. You will be asked to have an electric
periodic basis;
nerve test at regular intervals.).
Dishman discloses periodic monitoring and evaluation of patients:
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
53

weekly blood tests and follow-up.);
Id. at 901 (After each weekly follow-up appointment, the
pharmacist faxes a tracking sheet containing an evaluation of the
patient to the NCCC.).
g. obtaining said
second set of
information from
said patient; and
Ex. 1027, Fudin Decl. 155-59.

Powell discloses periodic monitoring and evaluation of patients:
Ex. 1006 at 902 (Follow-up visits should be at monthly intervals
or less for the first 3 months to enable the clinician to detect side
effects/early signs of toxicity.);
Id. at 903 (This treatment is monitored in the out-patients clinic,
initially with monthly visits. You will be asked to have an electric
nerve test at regular intervals.).
Dishman discloses periodic monitoring and evaluation of patients:
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.);
patient to the NCCC.).
h. entering said
second set of
information in
said medium
before said patient
is approved to
receive said drug.
Ex. 1027, Fudin Decl. 155-59.

Dishman discloses entering patient information in the computer
storage medium prior to treatment:
Ex. 1007 at 900 (emphasis added) (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);
54

patient to the NCCC and places the original document in the
patients medical record.).
Ex. 1027, Fudin Decl. 160-62.
16. The method of Powell discloses survey regarding patients compliance with risk
claim 15 wherein
avoidance measures:
said second set of Ex. 1006 at 901 (Patients should be specifically excluded from
information
treatment with thalidomide [if u]nlikely to be able to comply
comprises a survey with the prescribing instructions [or] considered not capable
regarding said
of complying with the requirements for reliable contraception.);
patients behavior
Id. (Women of childbearing potential should agree to stop
and compliance
taking thalidomide immediately should they miss a period, and
with said risk
urgently contact their prescribing physician. A pregnancy test
avoidance
should be provided and, if positive, appropriate counselling
measures.
should be given.);
Id. at 902 (Follow up visits should be at monthly intervals or
less for the first 3 months [and t]he warnings about the
possible toxicity and the need for adequate contraception should
be reinforced. Adequate time should be allowed to answer all
questions raised by the patient.).
Dishman discloses survey regarding patients compliance with risk
avoidance measures:
Ex. 1007 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.);
Id. at 901 (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.).
Ex. 1027, Fudin Decl. 163-69.
17. The method of Ex. 1027, Fudin Decl. 170.
claim 16 wherein
said survey is
conducted
telephonically
using an integrated
55

voice response
system.
18. The method of
claim 16 wherein
said patient is a
female of
childbearing
potential and said
second set of
information
comprises the
results of a
pregnancy test.
Powell teaches pregnancy test for women of childbearing

potential who are treated with thalidomide:
pregnancy test within 2 weeks prior to starting therapy.).
Dishman teaches requiring WBC tests every week before
prescribing the next week of drugs:

dispensing to a one-week supply.).
19. The method of Powell discloses pregnancy test prior to thalidomide therapy:
claim 18 wherein
said periodic
interval comprises pregnancy test within 2 weeks prior to starting therapy.).
about 28 days.
Dishman teaches weekly supply of medication:
Ex. 1027, Fudin Decl. 171, 173-79.
20. The method of Powell teaches informing patients regarding adequate
claim 1 further
contraception:
comprising
Ex. 1006 at 903 (Your doctor can advise you about adequate
providing said
contraception.).
patient with a
Ex. 1027, Fudin Decl. 139, 149-53.
contraceptive
device or
formulation.
21. The method of Powell discloses teratogenic side effects:
claim 1 wherein
said adverse side
effect comprises a teratogen.);
teratogenic effect.
56

be recognized, and addressed in each and every patient.).
Ex. 1027, Fudin Decl. 140, 142-53.
22. The method of Powell discloses guidelines for treatment of patients with
claim 1 wherein
thalidomide:
said drug is
Ex. 1006 at 901 (Guideline for the clinical use and dispensing of
thalidomide.
Thalidomide.).
23. The method of
claim 21 wherein
said teratogenic
effect is likely to
arise in a foetus
carried by said
patient.
Powell discloses teratogenic effect likely to arise in a foetus:

potential.);

should be given.).
24. The method of Powell discloses teratogenic effect likely to arise in a foetus:
claim 21 wherein
said teratogenic
effect is likely to
arise in a foetus
carried by a
recipient of the
bodily fluid of said who wish to become pregnant. e. Women of childbearing
potential.);
patient.
should be given.).
Ex. 1027, Fudin Decl. 140, 144-47.
25. The method of Ex. 1027, Fudin Decl. 140, 144-47.
claim 24 wherein
said recipient of
57

the bodily fluid of
said patient is a
sexual partner of
said patient.
26. The method of
claim 21 wherein
said set of
information
includes the
results of a
pregnancy test.
Powell teaches pregnancy test for women of childbearing

potential who are treated with thalidomide:
should be given.).
Dishman similarly teaches pregnancy test:
Ex. 1007 at 900 (contraindications to clozapine therapy include
pregnancy.).
Ex. 1027, Fudin Decl. 172-73.

27. The method of Powell discloses pregnancy test prior to thalidomide therapy:
claim 26 wherein
said prescription is instituting therapy with thalidomide, specifically by a negative
filled for no more pregnancy test within 2 weeks prior to starting therapy.).
than about 28
Dishman teaches weekly supply of medication:
days.
28pre and (a)(e).
28. wherein said
adverse side effect
is likely to arise in
patients who take
said drug in
combination with
Ex. 1027, Fudin Decl. 172, 178-80.

See, supra Claim 1pre and (a)-(e).
Powell teaches the risks of teratogenicity and peripheral
neuropathy in patients:
patient.).
58

at least one other
drug.
Dishman teaches agranulocytosis:

Ex. 1007 at 899 (Patients are monitored for agranulocytosis
.).
Ex. 1027, Fudin Decl. 181, 183-84.

29. The method of Dishman discloses guidelines for extensive patient evaluation:
claim 28, wherein Ex. 1007 at 900 (The NCCC guidelines require extensive
said set of
information is also examination, including laboratory testing and
probative of the
likelihood that
Ex. 1027, Fudin Decl. 185-94.
said patient may
take said drug and
said other drug in
combination.
30. The method of Powell discloses that the information includes diagnostic test
claim 28 wherein
results:
said set of
Ex. 1006 at 901(Pregnancy should be excluded before
information
includes the
results of
diagnostic testing. Id. at 903 (Thalidomide is toxic to the developing baby.);
commenced.);
Id. at 902 (All adverse events should be recorded and serious
events notified to the Clinical Trials Section, Medicines Control
Agency.).
Dishman discloses information containing diagnostic test results:
Ex. 1007 at 900 (The NCCC guidelines require extensive
31. The method
claim 30 wherein
said diagnostic
testing comprises
testing for
Ex. 1027, Fudin Decl. 181, 185-89.

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,
59

evidence of the
use of said other
drug.
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 electrocardiographic analysis, is
required.).
Ex. 1027, Fudin Decl. 181, 190-202.

32. The method of Dishman discloses extensive patient evaluation and teaches that
claim 30 wherein
its clozapine regime may be contraindicated for those with
substance abuse problems:
said diagnostic
testing comprises Ex. 1007 at 900 (The NCCC also recommends that clozapine
for evidence
not be used in patients who, because of social situation,
which is indicative substance abuse, or other factors, cannot be relied upon to keep
of the onset of
follow-up appointments.).
said adverse side
Id. (The NCCC guidelines require extensive patient evaluation
effect.
and documentation. A complete physical examination,
including laboratory testing and electrocardiographic analysis, is
required.).
Ex. 1027, Fudin Decl. 181, 185-89.
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/

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Paper No.

Patent No. 6,315,720

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

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

IV. 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

VI. DETAILED EXPLANATION OF THE CHALLENGE .................................. 17

Patent No. 6,315,720

Claim 1 is obvious over Powell in view of Dishman and in further

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 Powell,

VII. CONCLUSION ........................................................................................................... 60

Patent No. 6,315,720

Abbott Labs v. Andrx Pharms., Inc.,

Patent No. 6,315,720

37 C.F.R. 42.103 .................................................................................................................. 3

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,