··-____________ ..,.
`
`I,
`i ·.
`,,,
`
`-
`
`'/'
`
`I
`
`~__.:.__·-~ - -~- -
`I
`I \.
`
`'-.
`
`-·-----
`
`·-l
`
`I
`
`I
`
`I
`
`PATENT NUMBER
`\ .
`8316720
`
`0 ll~~i!~~HI
`
`--
`
`U.S. UTILITY Patent Applil.:aiion
`PATENT DATE
`
`NOV 13 2001
`
`r
`
`APPLICATION NO.
`O'J I Ci ~J/l.? 1 7
`
`CONT/PRIOR
`
`CLASS ·"
`(_,(l(j
`
`SUBCLASS
`
`:-'l-:.....,r."""'.)
`
`ART UNIT
`:3 r:·ic.
`
`,,
`
`i>'•lf1:-
`(:1 111:>"'
`'I
`l•l:i :i_
`I: '·'Iii i. 1'1 -:: I-
`_I' ,_, .-: ·:•1 :·\ I
`
`l
`
`EXAM IN&~
`\)\I i
`
`, _ _..
`
`l'
`
`1·-i,···,I: I >1_·1·.l·
`t '· J I J·' J
`:.:, ! .'! ··:-. (-'.~ r, J ;·:·1 :·/
`
`I .! J
`
`1.
`
`1: '•' ·11.·, -·::,
`
`i·:, __ ,, ...
`
`1:1'_:· ·1
`1· :1 ·r.
`·!·:. J· Ii::··
`
`·i_
`
`·,:f \ ';
`
`•'. ! i
`
`·1,·I·" i' , .. i
`; :1. I"·\"-:- 1:-'~ i
`l .t .i:,:1
`
`'-:i.
`:'.-'~-I·:·~
`
`1.·:1··1 !•'."I
`'. I 1 .. :i
`·. ·.
`~
`
`I __ ,·::_ I··
`,i_ 1:::'1· 1-I:·
`·l:.c:-:1
`1 L.
`(" ~ r·· f· i: :: ~- ·
`~ ,; . i '! • ) .,. .1 1 ·1
`
`r
`
`\ ' '
`
`PT0·2040
`1211111
`
`ISSUING CLASSIFICATION
`
`CROSS REFERENCE(S)
`
`ORIGINAL
`
`CLASS
`
`60 0
`
`I
`
`SUBCLASS
`300
`INTERNATIONAL CLASSIFICATION
`
`IA ~ I B s /r;:;o
`
`CLASS
`Z~S-
`
`SUBCLASS (ONE SUBCLASS PER BLOCK)
`3;z.~
`
`l ., Continued on Issue Slip Inside File Jacket
`
`DTERMINAL
`DISCLAIMER
`
`DRAWINGS
`
`.'
`
`CLAIMS ALLOWED
`
`Sheets Drwg.
`
`Figs. Drwg.
`
`Print Fig.
`
`Total Claims
`
`-'
`
`3 2..
`
`Print Claim for O.G.
`
`i
`
`NOTICE OF ALLOWANCE MAILED
`
`0 The te\Tll of this patent
`subsequent to _ · - - - (dale)
`has been dlsclalmed.
`D
`The teJTTl of this patent shall
`not extend beyond \he expiration date
`
`of U.S Patent No. - - - - -
`
`- - - - - -
`
`[J The terminal _months of
`this patent have bean disclaimed.
`
`-
`,.,.,.. ______
`
`--
`-
`
`· \A88lclnnt Ex.miner)
`
`.
`
`V?.o5~tJ1
`
`(Dal~)
`
`1'
`
`ERIC F. WINm.Uf4
`PRIMARY~~~
`
`y;'-=--
`
`__ ,,
`
`-------·
`(PrlmBry Examlnar)
`
`~t( r' I\' r
`-
`ISSUE FEE~_ t~x~~
`CJ..:zr>-rJ" t
`
`7}_1/01 _
`
`(Dat•)
`
`Amount Due
`
`JJ4ot
`
`Date Paid
`
`----
`
`(Leg~I ln•lrum0n11 Examiner)' ~-
`
`ISSUE BATCH NUMBER
`·--· C) 0
`'- .
`--
`
`.
`
`)
`
`WARNING:
`The lnform11t\on disclosed herein may bll reetrlcted. Unauthor\?ed dl11closure may be prohibited by the United States Code Title ~Ei. Sections 122, 161 and 366.
`Poes6sslon out11lde the U.S. Patent & Trademark Office Is reetrlcted to, authorized employees and contractor~ only.
`
`Form PT0·438A
`(R•v. 6(99)
`
`FILED WITH: D DISK (CRF) D FICHE D CD-ROM
`
`(Attached In pookat on right lnolda flllp)
`
`/' Ir
`
`I
`
`(FACE)
`
`CFAD VI 1002-0001
`
`

`

`JC841 U.S. PTO
`
`09/694217
`I lll/l~lg y~ ~~~f lllll l////111
`
`CONTENTS
`Date Received
`(Incl. C. of M.)
`or
`Date Malled
`
`INITIAOLS '1 ') ~\ t\')
`. NOV . .: { H
`
`•'
`
`.; '
`• )
`
`Date Received
`(Incl. c. Of M.)
`or
`Date Malled
`
`I
`
`I
`
`.'' ',
`
`-~-
`
`papers.
`
`47. _ __ _ __ _
`
`48. ___ ____ _
`
`49. - - - - - - - -
`
`50. _______ _ ___
`
`. 51. - - - - - - - - - - - - -
`52. _______ _
`
`12. _ ________ _
`
`53. _______ _
`
`13._ - - - - - - - -
`14. _______ _
`
`'
`
`: 15. - - - - - - - -
`'
`'16. ____ __ _ _
`
`: 17. __ _ ___ _ _ _
`'
`
`; 18._ - - - - - - - - - - (cid:173)
`: 19. - - - - - ' - - - - - - -
`20. _______ _
`
`21. _______ _
`
`22. _____ _ _
`
`-
`
`-
`
`23.
`24. _______ _
`
`- - -
`26. ___ ___ __ __ - - - -
`: 26. _______ _
`
`:, 27._~------
`
`'' '
`
`28. - - - - - - - -
`
`1.'·
`
`'
`
`'I 32.
`
`- - - - - - , ' . , - - - - -
`'I
`
`,'"
`
`-1
`
`·,,
`
`------~
`;! 34.
`-
`. ,·
`'',/
`::, < 35. - - - - - - -
`36.~-------
`37. - - - - - - -
`
`.\:
`
`38. ~-------
`
`39. - - - - - - -
`
`. :. 40. - - - - - - - - -
`',1
`
`- - -
`
`54 .. · - - - - - - : - - - -
`55. ________ _
`
`56. _______ _
`
`57. _______ _
`
`68. _______ _
`
`59. _______ _
`
`60. - - - - - - -
`61. __ _____ _
`62. _______ _ - - -
`63. - - - - - - - -
`64. ________ _
`
`65. - - - - - - - -
`66. _______ _
`
`- - - , - - - - - -
`
`~--~
`
`67. __ __ ___ ~
`
`68. ________ _
`
`69. _______ _
`
`70. _______ _
`
`71.~-------
`72. _______ _
`
`73. ______ _
`
`74. -------~
`75. _______ ~
`- - -
`
`76. _ _ ____ _
`
`77. _ _ ~-----
`78. _______ _
`
`79. -----~-.,--
`
`,.
`
`80. - -_ _ _ , . - - - - - -
`
`81. __ ~~----
`82. ~------~
`
`,,
`41. - - - - - - - - -
`\
`,
`)
`
`(LEFT OUTSIDE)
`
`CFAD VI 1002-0002
`
`

`

`PATENT APPLICATION SERIAL NO . - - - - - - - - -
`
`U.S. DEPARTMENT OF COMMERCE
`PATENT AND TRADEMARK OFFICE
`FEE RECORD SHEET
`
`10/2G/2000 JBALIHAH 00000014 09&94217
`01 FC:101
`710.00 OP
`02 FC:103
`21G.OO OP
`
`PT0-1556
`(5/87)
`
`·u.s. GPO: 1~4eo-oe2!\SH4
`
`J
`
`~-------------------~
`
`CFAD VI 1002-0003
`
`

`

`Page 1 of 1
`
`COMMIS!l\ONrn !"OR PATEN""P.J
`UN!T~D STATES fAT~NT ANO TAADC.MARK OFF!O~
`Vio.8HING'llCN, Q_C, 2023\
`www.uspto.gov
`
`CLASS
`600
`
`GROUP ART UNIT
`3"136
`
`ATTORNEY
`DOCKET NO.
`CELG-0188
`
`-
`
`B4~LL bt7rr~
`
`STATE OR
`COUNTRY
`NJ
`
`SHEETS
`DRAWING
`-
`
`TOTAL
`CLAIMS
`32
`
`INDEPENDENT
`CL.AIMS
`1
`
`-
`
`-
`
`11811 ~!I!~ ~I II ~II~ ~II II llt lml 11111 IUI
`Bib Deita Shoot --
`
`SERIAL NUMBER
`09/694,217
`
`FILING DATE
`10/23/2000
`RULE
`-
`
`APPLICANTS
`Bruce A. Williams, Flemlngton, NJ ;
`Joseph K. Kaminski, Hampton, NJ ;
`
`-
`
`EQUIRED, FOREIGN FILING LICENSE
`GRANTED ** 12/1112000
`
`'"'CONTINUING DATA******"**""***********'""*
`Yc ti P n..:=
`/Ji OREIGN APPLICATIONS *""***""***u"*****"'
`lffii l'2 , /1 .c...-
`Foreign Priority claimed Q yes~ no
`--- -------
`)5 use 119 (a·d) conditions D yes ~ no D Meil altar
`/t.fv
`met
`All
`- -,,.,, " Signature
`Verified end
`Acknowledged
`-
`ADDRESS
`
`Initials
`
`John W. Caldwell
`WOODCOCK WASHBURN KURTZ
`MACKIEWICZ & NORRIS LLP
`One Liberty Place-46th Floor
`Philadelphia , PA 19103
`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
`
`FILING FEE FEES: Authority has been given in Paper
`RECEIVED No.
`to charge/credit DEPOSIT ACCOUNT
`No.
`for following:
`926
`
`=
`
`.. >;
`
`IQ All Fees
`ID 1.16 Fees ( Filln~)
`Q 1.17 Fees ( Processing Ext. of
`time)
`11:1 1.18 Fees ~Issue)
`IQ Other
`ID Credit
`
`I
`I
`
`l
`I
`I
`
`file ://C: \APP S\preexam \correspondence\ l _A. xml
`
`12/i 3
`
`CFAD VI 1002-0004
`
`

`

`. -u .
`. ~n
`.......... ~\O I
`,__
`c:::>-~
`. <.-.>-
`:---~
`.
`' c:::>-~
` -:!: -0 DOCKET NO. : CELG-0188
`I~ C
`
`IN THE UNITE:O STATES PATENT AND TRADEMARK OFFICE
`
`In Re Application of:
`Bruce A. Williams and Joseph K. Kaminski
`
`Serial No.: Not assigned
`
`Group Art Unit: Not assigned
`
`Filing D.ate: October 23, 2000
`
`Examiner: Not assigned
`
`For; 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
`
`EXPRESS MAIL LABEL NO: EV568026755US
`DATE OF DEPOSIT: October 23, 2000
`
`Box
`
`181 Patent Application
`D Provisional 0 Design
`
`Assistant Commissioner for Patents
`Washington DC 20231
`
`Sir:
`
`PATENT APPLICATION TRANSMITTAL LETTER
`
`Transmitted herewith for filing, please find
`
`A Utility Patent Application under 37 C.F.R. l.53(b).
`
`It is a continuing application, as follows:
`
`D continuation 0 divisional 0 continuation-in-part of prior application number
`_! ___ _
`
`D
`D
`
`A Provisional Patent Application under 37 C.F.R. l.53(c).
`
`A Design Patent Application (submitted in duplicate).
`
`Including the following:
`
`1
`
`: c:::> . .
`
`I.
`
`CFAD VI 1002-0005
`
`

`

`CJ
`
`'° en
`•JJ
`r"
`'1" ru
`~·
`"'~
`r.~
`C:l
`rtl
`IJ,!
`C)
`t~
`
`~
`
`DOCKET NO. : CELG-0188
`
`- 2 -
`
`PATENT
`
`D
`
`181
`
`D
`
`D
`
`Provisional App licarion Cover Sheet.
`
`New or Revised Specification, including pages J_ to _JL containing:
`
`~
`181
`181
`D
`
`Specification
`
`Claims
`
`Abstract
`
`Substitute Specification, including Claims and Abstract.
`
`D
`
`D
`
`The present application is a continuation application of Application
`. The present application includes the
`No.
`filed
`Specification of the parent application which has been revised in
`accordance with the amendments filed in the parent application. Since
`none of those amendments incorporate new matter into the parent
`application, the present revised Specification also does not include new
`matter.
`
`The present application is a continuation application of Application
`, which in turn is a continuation-in-part of
`No.
`filed
`Application No.
`filed
`. The present application
`includes the Specification of the parent application which has been
`revised in accordance with the amendments filed in the parent
`application. Although the amendments in the parent C-1-P application
`may have incorporated new matter, since those are the only revisions
`included in the present application, the present application includes no
`new matter in relation to the parent application.
`
`A copy of earlier application Serial No.
`Filed------
`including Specification, Claims and Abstract {pages 1 - @@), to which no new
`matter has been added TOGETHER WITH a copy of the executed oath or declara~ion
`for such earlier application and all drawings and appendices. Such earlier application
`is hereby incorporated into the present application by reference.
`
`Please enter the following amendment to the Specification under the Cross-Reference
`to Related Applications section (or create such a section) : "This Application:
`D is a continuation of 0 is a divisional of 0 claims benefit of U.S. provision~!
`Application Serial No.
`f i l ed - - - - - - - - - - - -
`
`CFAD VI 1002-0006
`
`

`

`DOCKET NO. : CELG-0188
`
`-3-
`
`PATENT
`
`D
`
`0
`
`D
`
`D
`
`Signed Statement attached deleting inventor(s) named in the prior application.
`
`A Preliminary Amendment.
`
`Sheets of D Formal D Informal Drawings.
`
`Petition to Accept Photographic Drawings.
`
`D
`
`Petition Fee
`
`An 181 Executed D Unexecuted Declaration or Oath and Power of Attorney.
`
`An Associate Power of Attorney.
`
`D
`
`An D Executed D Copy of Executed Assignment of the Invention to __ __ _
`
`0
`0
`
`D
`
`D A Recordation Form Cover Sheet.
`0 Recordation Fee - $40.00.
`The prior application is assigned ofrecord to - - - - - -
`
`Priority is claimed under 35 U.S.C. § 119 of Patent Application No. _____ _
`filed
`m
`(country).
`D
`A Certified Copy of each of the above applications for which priority is
`claimed:
`0 is enclosed.
`D has been filed in prior application Serial No. ___ filed _ _ _
`
`An D Executed or 0 Copy of Executed Earlier Statement Claiming Small Entity
`Status under 37 C.F.R. 1.9 and 1.27
`D is enclosed.
`D has been filed in prior application Serial No.
`said status is still proper and desired in present case.
`
`filed --~
`
`CFAD VI 1002-0007
`
`

`

`DOCKET NO. : CELG-0188
`
`-4-
`
`PATENT
`
`D
`
`D
`
`D
`
`D
`
`D
`
`D
`
`C8:J
`
`D
`
`Diskette Containing DNA/ Amino Acid Sequence Information.
`
`Statement to Support Submission of DNA/Amino Acid Sequence Information.
`
`The computer readable form in this application
`, is identical with that filed in
`Application Serial Number
`, filed
`In accordance with 37 CFR
`l.82l(e), please use the D first-filed, D last-filed or D only computer readable
`form filed in that application as the computer readable form for the instant
`application. It is understood that the Patent and Trademark Office will make the
`necessary change in application number and filing date for the computer readable
`form that will be used for the instant application. A paper copy of the Sequence
`Listing is D included in the originally-filed specification of the instant application,
`D included in a separately filed preliminary amendment for incorporation into the
`specification.
`
`Information Disclosure Statement.
`D
`D
`
`Attached Form 1449.
`
`Copies of each of the references listed on the attached Form PT0-1449 are
`enclosed herewith.
`
`A copy of Petition for Extension of Time as filed in the prior case.
`
`Appended Material as follows: - - - - - - - - - - - - - - - - - -
`
`Return Receipt Postcard (should be specifically itemized).
`
`Other as follows: - - - - - - - - - - - - - - - - - - - - - - -
`
`CFAD VI 1002-0008
`
`

`

`DOCKET NO. : CELG-0188
`
`- 5 -
`
`PATENT
`
`FEE CALCULATION:
`
`D
`
`of the prior application before
`Cancel in this application original claims
`calculating the filing fee. (At least one original independent claim must be retained
`for filing purposes.)
`
`r
`
`t
`:
`• c
`
`I
`
`SMALL ENTI1Y
`
`NOT SMALL ENTI1Y
`
`RATE
`
`FEE
`
`RATE
`
`FEE
`
`PROVISIONAL APPLICATION
`
`DESIGN APPLICATION
`
`UTTLl1Y APPLICATIONS BASE FEE
`
`$75.00
`
`$160.00
`
`$355.00
`
`UTILI1Y APPLICATION; ALL CLAIMS
`CALCULATED AFTER ENTRY OF ALL
`AMENDMENTS
`
`No. Extra
`
`•""I TOTAL
`
`32 - 20-
`
`12
`
`~ . ••• CLAIMS
`----------·- - No, Filed
`-------
`-------
`II ... INDEP.
`~. CLAIMS
`••
`... :. FIRST PRESENT A TTON OF MULTIPLE
`.. .
`•••• DEPENDENT CLAIM
`ADDITIONAL FILING FEE
`
`1 - 3 00
`
`0
`
`I
`
`I
`
`TOT AL FILING FEE DUE
`
`$9 each
`
`$40 each
`
`$135
`
`$
`
`$
`
`$
`
`$
`
`$
`
`$
`
`$
`
`$
`
`$150.00
`
`$320.00
`
`$710.00
`
`$
`
`$
`
`$710.00
`
`$18 each
`
`$216.00
`
`$80 each
`
`$ 0
`
`$270
`
`$
`
`$
`
`$926.00
`
`A Check is enclosed in the amount of$ 926.00 .
`
`181
`
`The Commissioner is authorized to charge payment of the following fees and to
`refund any overpayment associated with this communication or during the pendency
`of this application to deposit account 23-3050. This sheet is provided in duplicate.
`
`0
`
`181
`
`D
`
`The foregoing amount due.
`
`Any additional filing fees required, including fees for the presentation of extra
`claims under 3 7 C.F .R. 1.16.
`
`Any additional patent application processing fees under 37 C.F.R. 1.17 or
`l.20(d).
`
`The issue fee set in 3 7 C.F .R. 1.18 at the mailing of the Notice of Allowance.
`
`18]
`
`The Commissioner is hereby requested to grant an extension of time for the .
`appropriate length oftime, should one be necessary, in connection with this filing or
`any future filing submitted to the U.S. Patent and Trademark Office in the above-
`
`CFAD VI 1002-0009
`
`

`

`DOCKET NO. : CELG-0188
`
`-6-
`
`PATENT
`
`identified application during the pendency of this application. The Commissioner is
`further authorized to charge any fees related to any such extension of time to deposit
`account 23-3050. This sheet is provided in duplicate.
`
`SHOULD ANY DEFICIENCIES APPEAR with respect to this application, including
`deficiencies in payment of fees, missing parts of the application or otherwise, the United
`States Patent and Trademark Office is respectfully requested to promptly notify the
`
`undersigned.
`
`Date:
`
`Woodcock Wash bum Kurtz
`Mackiewicz & Norris LLP
`One Liberty Place - 46th Floor
`Philadelphia PA 19103
`Telephone: (215) 568-3100
`Facsimile: (215) 568-3439
`
`s.~~:Y#H
`
`Registration No. 43,966
`
`e I 997 WWKMN
`
`CFAD VI 1002-0010
`
`

`

`DOCKET NO. : CELG-0188
`
`PATENT
`
`IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
`
`In Re Application of:
`Bruce A. Williams and Joseph K. Kaminski
`
`Serial No.: Not assigned
`
`Group Art Unit: Not assigned
`
`Filing Date: October 23, 2000
`
`Examiner: Not assigned
`
`For: 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
`
`EXPRESS MAIL LABEL NO: EL5680267!5!5US
`DATE OF DEPOSIT: October 23, 2000
`
`Box
`
`181 Patent Application
`D Provisional D Design
`
`Assistant Commissioner for Patents
`Washington DC 20231
`
`Sir:
`
`PATENT APPLICATION TRANSMITTAL LETTER
`
`Transmitted herewith for filing, please find
`
`A Utility Patent Application under 37 C.F.R. l.53(b).
`
`It is a continuing application, as follows:
`
`D continuation D divisional D continuatie>n-in-part of prior application number
`_ / __ _
`
`D
`D
`
`A Provisional Patent Application under 37 C.F.R. l.53(c).
`
`A Design Patent Application (submitted in duplicate).
`
`Including the following:
`
`CFAD VI 1002-0011
`
`

`

`DOCKET NO. : CELG-0188
`
`-2-
`
`PATENT
`
`D
`
`181
`
`D
`
`D
`
`Provisional Application Cover Sheet.
`
`New or Revised Specification, including pages _l_ to --12_ containing:
`
`181
`181
`181
`D
`
`Specification
`
`Claims
`
`Abstract
`
`Substitute Specification, including Claims and Abstract.
`
`D
`
`D
`
`The present application is a continuation application of Application
`No.
`filed
`. The present application includes the
`Specification of the parent application which has been revised in
`accordance with the amendments filed in the parent application. Since
`none of those amendments incorporate new matter into the parent
`application, the present revised Specification also does not include new
`matter.
`
`The present application is a continuation application of Application
`No.
`filed
`, which in tum is a continuation-in-part of
`Application No.
`filed
`. The present application
`includes the Specification of the parent application which has been
`revised in accordance with the amendments filed in the parent
`application. Although the amendments in the parent C-1-P application
`may have incorporated new matter, since those are the only revisions
`included in the present application, the present application includes no
`new matter in relation to the parent application.
`
`A copy of earlier application Serial No. ______ Filed _____ _
`including Specification, Claims and Abstract (pages 1 - @@), to which no new
`matter has been added TOGETHER WITH a copy of the executed oath or declaration
`for such earlier application and all drawings and appendices. Such earlier application
`is hereby incorporated into the present application by reference.
`
`Please enter the following amendment to the Specification under the Cross-Reference
`to Related Applications section (or create such a section) : "This Application:
`
`Dis a continuation of Dis a divisional of D claims benefit of U.S. provisional
`Application Serial No.
`f i l ed - - - - - - - - - - - -
`
`CFAD VI 1002-0012
`
`

`

`DOCKET NO. : CELG-0188
`
`- 3 -
`
`PATENT
`
`D
`
`D
`
`D
`
`D
`
`18]
`
`18]
`
`Signed Statement attached deleting inventor(s) named in the prior application.
`
`A Preliminary Amendment.
`
`Sheets of D Formal D Informal Drawings.
`
`Petition to Accept Photographic Drawings.
`
`D
`
`Petition Fee
`
`An 18] Executed D Unexecuted Declaration or Oath and Power of Attorney.
`
`An Associate Power of Attorney.
`
`D
`
`An D Executed D Copy of Executed Assignment of the Invention to ____ _
`
`D
`0
`
`D
`
`D A Recordation Form Cover Sheet.
`D Recordation Fee - $40.00.
`The prior application is assigned of record to - - - - - -
`
`Priority is claimed under 35 U.S.C. § 119 of Patent Application No . - - - - - -
`filed
`m
`(country).
`D
`
`A Certified Copy of each of the above applications for which priority is
`claimed:
`D is enclosed.
`D has been filed in prior application Serial No. ___ filed __ _
`
`An D Executed or D Copy of Executed Earlier Statement Claiming Small Entity
`Status under 37 C.F.R. 1.9 and 1.27
`D is enclosed.
`D has been filed in prior application Serial No.
`said status is still proper and desired in present case.
`
`filed -~-
`
`CFAD VI 1002-0013
`
`

`

`DOCKET NO. : CELG-0188
`
`-4-
`
`PATENT
`
`0
`
`D
`
`D
`
`D
`
`0
`
`D
`
`181
`
`Diskette Containing DNN Amino Acid Sequence Information.
`
`Statement to Support Submission of DNA/ Amino Acid Sequence Information.
`
`The computer readable form in this application
`, is identical with that filed in
`Application Serial Number
`, filed
`In accordance with 37 CPR
`l.821(e), please use the 0 first-filed, D last-filed or 0 only computer readable
`foim filed in that application as the computer readable form for the instant
`application. It is understood that the Patent and Trademark Office will make the
`necessary change in application number and filing date for the computer readable
`form that will be used for the instant application. A paper copy of the Sequence
`Listing is 0 included in the originally-filed specification of the instant application,
`D included in a separately filed preliminary amendment for incorporation into the
`specification.
`
`Info1mation Disclosure Statement.
`D
`D
`
`Attached Form 1449.
`
`Copies of each of the references listed on the attached Form PT0-1449 are
`enclosed herewith.
`
`A copy of Petition for Extension of Time as filed in the prior case.
`
`Appended Material as follows:
`
`Return Receipt Postcard (should be specifically itemized).
`
`CFAD VI 1002-0014
`
`

`

`DOCKET NO. : CELG-0188
`
`- 5 -
`
`PATENT
`
`FEE CALCULATION:
`
`D
`
`of the prior application before
`Cancel in this application original claims
`calculating the filing fee. (At least one original independent claim must be retained
`for filing purposes.)
`
`SMALL ENTITY
`
`NOT SMALL ENTITY
`
`RATE
`
`FEE
`
`RATE
`
`--
`
`FEE ~
`P.,
`
`-~
`
`
`Ul
`-::
`~
`•
`I l
`
`.
`
`PROVlSIONAL APPLICATION
`
`DESIGN APPLICATION
`
`UTILITY APPLICATIONS BASE FEE
`
`$75.00
`
`$160.00
`
`$355.00
`
`UTILITY APPLICATION; ALL CLAIMS
`CALCULATED AFTER ENTRY OF ALL
`AMENDMENTS
`
`No. Extra
`
`32- 20 =
`
`12
`
`1 - 3 -
`
`0
`
`-----
`------- No. Filed
`-·-----
`-------
`Yl TOTAL
`.. v CLAIMS
`l
`.... INDEP.
`l._l
`....
`.... CLATMS
`...
`....
`y. FIRST PRESENTATION OF MULTIPLE
`• •
`•••• DEPENDENT CLAIM
`ADDITIONAL FILING FEE
`
`TOTAL FlLINGFEE DUE
`
`$9 each
`
`$40 each
`
`$135
`
`$
`
`$
`
`$
`
`$
`
`$
`
`$
`
`$
`
`$
`
`$150.00
`
`$320.00
`
`$
`
`$
`
`$710.00
`
`$710.00
`
`$18 each
`
`$216.00
`
`$80 each
`
`$ 0
`
`$270
`
`$
`
`$
`
`$926.00
`
`.:i,</.1:j
`
`[81
`181
`
`181
`
`A Check is enclosed in the amount of$ 926.00 .
`
`The Commissioner is authorized to charge payment of the following fees and to
`refund any overpayment associated with this communication or during the pendency
`of this application to deposit account 23-3050. This sheet is provided in duplicate.
`
`D
`181
`
`181
`
`D
`
`The foregoing amount due.
`
`Any additional filing fees required, including fees for the presentation of extra
`claims under 37 C.F.R. 1.16.
`
`Any additional patent application processing feea under 3 7 C.F .R. 1.17 or
`l.20(d).
`
`The issue fee set in 37 C.F.R. 1.18 at the mailing of the Notice of Allowance.
`
`The Commissioner is hereby requested to grant an extension of time for the
`appropriate length of time, should one be necessary, in connection with this filing or
`any future filing submitted to the U.S. Patent and Trademark Office in the above-
`
`CFAD VI 1002-0015
`
`

`

`DOCKET NO. : CELG-0188
`
`-6-
`
`PATENT
`
`identified application during the pendency of this application. The Commissioner is
`further authorized to charge any fees related to any such extension of time to deposit
`account 23-3050. This sheet is provided in duplicate.
`
`SHOULD ANY DEFICIENCIES APPEAR with respect to this application, including
`deficiencies in payment of fees, missing parts of the application or otherwise, the United
`States Patent and Trademark Office is respectfully requested to promptly notify the
`undersigned.
`
`Date:
`
`S. Mauri
`Registration No. 43,966
`
`Woodcock W ashbum Kurtz
`Mackiewicz & Norris LLP
`One Liberty Place - 46th Floor
`Philadelphia PA 19103
`Telephone: (215) 568-3100
`Facsimile: (215) 568-3439
`
`IC 1997 WWKMN
`
`CFAD VI 1002-0016
`
`

`

`CELG-0188
`
`PATENT
`
`METHODS FOR DELIVERING A DRUG TO A PATIENT
`WHILE AVOIDIJ~~G THE OCCURRENCE OF AN ADVERSE SIDE
`EFFECT KNOWN OR SUSPECTED OF BEING CAUSED BY THE DRUG
`
`FIELD OF THE INVENTION
`
`5
`
`The present invention relates to improved methods for delivering a drug to a
`
`patient. More particularly, the present invention relates to novel methods for delivering
`
`a teratogenic or other potentially hazardous drug to a patient in need of the drug, while
`
`avoiding the occurrence of known or suspected side effects of the drug. The novel
`
`methods permit the distribution to patients of drugs, particularly teratogenic drugs, in
`
`10
`
`ways wherein such distribution can be carefully monitored and controlled.
`
`BACKGROUND OF THE INVENTION
`
`Many beneficial drugs are known or suspected of producing adverse side effects
`
`in certain individuals. These side effects may be manifest in the patient talcing the drug,
`
`in a foetus (i.e. fetus) carried by the patient, or in a recipient (or foetus carried by a
`
`15
`
`recipient) of the bodily fluids of the patient. In some cases, administration of the drug
`
`may be acceptable in some patients, but absolutely contraindicated in other patients.
`
`For example, drugs known or suspected of causing birth defects if taken by a pregrtant
`
`woman (i.e. teratogenic drugs), may nonetheless. be beneficial for treating certain
`
`conditions. However, because of the teratogenic properties of the drug, administration
`
`20
`
`to pregnant women must be avoided. Other drugs are known which may be beneficially
`
`employed in the general population, but must be avoided by individuals having a certain
`
`.I-
`
`CFAD VI 1002-0017
`
`

`

`CELG-0188
`
`-2-
`
`PATENT
`
`preexisting condition, or those concurrently taking certain other medication(s), due to
`
`adverse side effects which may develop in those individuals.
`
`One such drug which is known to produce adverse side effects, but which may
`
`nevertheless be beneficially employed in certain patients is thalidomide. Thalidomide is
`
`5
`
`a drug which was first synthesized in Germany in 1957. Beginning in 1958, it was
`
`marketed in many countries for use as a sedative, although it was never approved for
`
`use in the United States. After reports of serious birth defects, thalidomide was
`
`withdrawn from all markets by 1962. However, during the years it was used, it was
`
`found to be effective in treating erythema nodosum leprosum (ENL ), a condition of
`
`10
`
`leprosy, and the U.S. Food and Drug Administration (FDA)has made the drug available
`
`for this specific use via a program of the Public Health Service. More recently,
`
`investigators have found that thalidomide may be effective in treating AIDS wasting
`
`and aphthous ulcers occurring in AIDS patients. In addition, treatments for other
`
`diseases, such as a number of neoplastic diseases including cancers, rheumatoid
`
`15
`
`arthritis, and macular degeneration, are also believed to be possible. The FDA has
`
`recently approved an application by Celgene Corporation, whlch is the assignee of the
`
`present patent application, to market thalidomide for the treatment ofENL. The
`
`medical community anticipates that thalidomide will be used for treatment of additional
`
`conditions and diseases, including those set forth above. However, due to the severe
`
`20
`
`teratogenic risk of thalidomide, methods are needed to control the distribution of this
`
`drug so as to preclude administration to foetuses.
`
`In this regard, U.S. Patent No. 6,045,501, to Elsayed et al., provides methods for
`
`delivering a drug to a patient while preventing the exposure of a foetus or other
`
`contraindicated individual to the drug. According to the methods of this patent,
`
`25
`
`prescriptions for the drug are filled only after a computer readable storage mediUIJI: has
`
`been consulted to assure that the prescriber is registered in the medium and qualified to
`
`prescribe the drug, that the pharmacy is registered in the medium and qualified to fill
`
`the prescription for the drug, and the patient is registered in the medium and approved
`
`to receive the drug. Improvements to this method may be useful, however, to minimize
`
`30
`
`and simplify the demands on the pharmacy, thereby improving compliance with the
`
`0
`~tr
`al
`tJJ
`+:
`i'l)
`~ ". 11,1
`
`!;'
`~.
`Cl
`
`MJ uJ
`a
`c~
`
`CFAD VI 1002-0018
`
`

`

`-----------~--·- --
`
`-
`
`-
`
`0
`\b~
`Qi
`
`'° .r. ru
`
`~i.
`\"-!
`
`II
`~~"
`C:)
`MJ w
`r.:i
`0
`
`CELG-0188
`
`-3-
`
`PATENT
`
`system of distribution, and reducing the risk that the drug will be dispensed to a
`
`contraindicated individual.
`
`Methods formonitoring and educating patients to whom a drug is distributed
`
`have been developed in connection with Accutane (isotretinoin). Accutane, which is a
`
`5
`
`known teratogen, is a uniquely effective drug for the treatment of severe, recalcitrant,
`
`nodular acne. A pregnancy prevention program was developed, and the Slone
`
`Epidemiology Unit of Boston University designed and implemented a survey to
`
`evaluate these efforts. The survey ident1fied relatively low rates of pregnancy during
`
`Accutane treatment, which suggests that such a program can be effective. With more
`
`10
`
`than about 325,000 women enrolled to date in the Accutane survey, it is also clear that
`such a large-scale study can be conducted. Enrollment in the Accutane survey is
`voluntary, however. Accordingly, assessing the representativeness of the women who
`
`have been enrolled in the survey has been problematic, and it has been difficult to
`
`determine whether the survey results can be generalized to all female Accutane users.
`
`15
`
`Thus, an improved survey is needed which would be representative of all users of a
`
`particular drug, such as thalidomide, who obtain the drug through legal distribution
`
`channels. There are also no mechanisms provided to assure compliance with the
`
`program or to limit distribution of the drug to participants in the survey.
`
`Because drug sharing may frequently occur among AIDS patients, which may
`
`20
`
`result in placing a foetus at risk, a program is needed which can be used to educate men
`
`and women about the risk of teratogenic drugs, such as thalidomide. In addition, a
`
`system is needed for the controlled distribution of a drug, in which of all users of the
`
`drug, including prescribers, pharmacies, and patients, may be accountable for their
`
`compliance with methods that may be established to minimize the risk that a
`
`25
`
`contraindicated individual will be exposed to the drug. The present invention is
`
`directed to these, as well as other important ends.
`
`SUMMARY OF THE INVENTION
`
`The present invention is directed to improved methods for delivering a drug to a
`
`patient in need of the drug, while avoiding the occurrence of an adverse side effect
`
`30
`
`known or suspected of being caused by the drug, of the type in which prescriptions for
`
`--... ·-
`
`CFAD VI 1002-0019
`
`

`

`CELG-0188
`
`- 4 -
`
`PATENT
`
`the drug are filled only after a computer readable storage medium has been consulted to
`
`assure that the pres~riber is registered in the medium and qualified to prescribe the drug,
`
`that the pharmacy is registered in the medium and qualified to fill the prescription for
`
`the drug, and the patient is registered in the medium and approved to receive the drng.
`
`5
`
`Jn one embodiment of the invention, there are provided improved methods comprising
`
`the steps of:
`
`a.
`
`defming a plurality of patient risk groups based upon a predefined set of
`
`risk parameters for the drug;
`
`b.
`
`defining a set of information to be obtained from the patient, which
`
`10
`
`information is probative of the risk that such adverse side effect is likely
`
`to occur if the drug is taken by the patient;
`
`in response to the information set, assigning the patient to at least one of
`
`the risk groups; and
`
`entering the risk group assignment in the medium before the patient is
`
`c.
`
`d.
`
`15
`
`approved to receive the drug.
`
`The improved methods described herein provide advantageous and effective
`
`means for monitoring, controlling and authorizing the distribution to patients of drugs
`
`known or suspected of causing adverse side effects. The methods of the present
`
`invention include a variety of checks and balances which serve to limit unauthorized
`
`20
`
`and possibly inappropriate distribution of the drug. These methods are particularly
`
`applicable to distribution of teratogenic drugs, in which case the checks and balances
`
`may be particularly advantageous for preventing distribution of the drug to patients
`
`whose use of the drng may pose an unacceptable risk that a foetus carried by the patient
`
`or a recipient of the bodily fluids of the patient will be exposed to such drugs.
`
`25
`
`Accordingly, the present methods may be advantageously used to avoid exposure of
`
`foetuses to teratogenic drugs, thereby avoiding the terrible birth defects which may
`
`result from such exposure.
`
`The invention is not limited to the distribution of teratogenic drugs; other
`
`potentially hazardous drugs may also be distributed in accordance with embodiments of
`
`30
`
`this invention and such drugs may be distributed in such a fashion that persons for
`
`CFAD VI 1002-0020
`
`

`

`CELG-0188
`
`-5-
`
`PATENT
`
`whom such drugs are contraindicated will not receive them. These and other aspects of
`
`the invention will become more apparent from the present description and claims.
`
`DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS
`
`The present invention is directed generally to methods for the delivery of drugs
`
`5
`
`known or suspected of causing an adverse side effect, especially teratogenic drugs, to
`
`patients. The term "drug," as used herein, refers to any substance which is intended for
`
`use in the diagnosis, cure, mitigation, treatment or prevention of disease, or to affect the
`
`structure or function of the body. The term "side effect" refers to any abnormality,
`
`defect, mutation, lesion, degeneration or injury which may be caused by talcing the
`
`10
`
`drug. The side effect may be one which is likely to arise in the patient or in a foetus
`
`(i.e., fetus) carried by the patient. The side effect may also be one which is likely to
`
`arise in a recipient of