(12) Unlted States Patent
`Buggy et a].
`
`(10) Patent N0.:
`(45) Date of Patent:
`
`US 8,754,090 B2
`*Jun. 17, 2014
`
`USOO8754090B2
`
`(54) USE OF INHIBITORS OF BRUTON’S
`TYROSINE KINASE (BTK)
`
`_
`.
`.
`(75) Inventors. Joseph J. Buggy, Mountaln YleW, CA
`(Us); Gwen Fyfe, San FranCISco, CA
`(US); David J. Loury, San Jose, CA
`(Us)
`
`(73) Assignee: Pharmacyclics, Inc., Sunnyvale, CA
`(Us)
`
`( * ) Notice:
`
`Subject to any disclaimer, the term of this
`patent is extended or adjusted under 35
`U30 1540’) by 0 days'
`This patent is subject to a terminal dis
`Clalmer'
`
`~
`
`(21) Appl- NO-I 13/3401522
`
`(22) Filed:
`
`Dec. 29, 2011
`
`Prior Publication Data
`
`us 2012/0183535 A1
`
`Jul. 19, 2012
`
`Related US. Application Data
`
`(63) Continuation of application No. 13/ 153,317, ?led on
`J _3 2011_
`un ’
`(60) Provisional application No. 61/351,130, ?led on Jun.
`
`3, 2010, provisional application No. 61/351,655, ?led on Jun. 4, 2010, provisional application No.
`
`61/351,793, ?led 011 Jun. 4, 2010, provisional
`appllcatlon No. 61/351,762, ?led on Jun. 4, 2010,
`provisional application No. 61/419,764, ?led on Dec.
`3, 2010, prOV1slonal appllcatlon No. 61/472,138, ?led
`on Apr_ 5, 2011_
`
`(2006.01)
`(200601)
`(200601)
`(200691)
`(2006.01)
`
`(51) Int Cl
`'
`'
`A61K 31/519
`A611, 35/00
`A611) 29/00
`A611” 35/02
`C07D 487/04
`(52) U_s_ CL
`USPC ...................................... .. 514/262.1; 544/262
`(58) Field of Classi?cation Search
`USPC ...................................... .. 514/262.1; 544/262
`See application ?le for complete search history.
`R f
`Ct d
`e erences 1 e
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`(commued)
`
`FOREIGN PATENT DOCUMENTS
`
`EP
`WO
`WO
`WO
`W0
`
`W0
`W0
`WO
`
`1473039
`WO-97-28161
`WO-99-54286
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`OTHER PUBLICATIONS
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`Hiddeman et a1. (Seminars in Oncology, 30, 1, 2, Feb. 2003, p.
`16-20).*
`
`iglly-ea et a1. (Poster Abitracts, Dec. 3, 2009, 51st ASH Annual
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`PRNewswire (Dec. 2009) and.*
`US. Appl. No 13/654,173, ?led Oct. 17, 2012, Honigberg et a1.
`US. Appl. No. 13/736,812, ?led Jan. 8, 2013, Buggy et a1.
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`U~S~APP1~ N°~ 13/747319, ?led Jim 22, 2013, Buggy et ill
`(Continued)
`
`Primary Examiner i Uma Ramachandran
`(74) Attorney, Agent, or Firm * Wilson, Sonsini, Goodrich
`-
`& Rosat1
`
`ABSTRACT
`(57)
`Disclosed herein are methods for treating a cancer compris
`ing: a. administering a Btk inhibitor to a subject suf?cient to
`result in an increase or appearance in the blood of a subpopu
`lation of lymphocytes de?ned by immunophenotyping; b.
`determining the expression pro?le of one or more biomarkers
`from one or more subpopulation of lymphocytes; and c.
`administering a second agent based on the determined
`expression pro?le.
`
`2 Claims, 39 Drawing Sheets
`
`Coalition for Affordable Drugs IV LLC – Exhibit 1001
`
`

`

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