(19) United States
`(12) Patent Application Publication (10) Pub. No.: US 2014/0219919 A1
`EDWARDS et al.
`(43) Pub. Date:
`Aug. 7, 2014
`
`US 20140219919A1
`
`(54) IL-11 RBINDING PROTEINS AND USES
`THEREOF
`
`(71) Applicant: CSL Limited, Parkville (AU)
`(72) Inventors: Kirsten EDWARDS, Parkville (AU):
`Matthew HARDY, Parkville (AU):
`Veronika RAYZMAN, Parkville (AU):
`Michael WILSON, Parkville (AU)
`
`(73) Assignee: CSL Limited, Parkville (AU)
`
`(21) Appl. No.: 14/174,009
`
`(22) Filed:
`
`Feb. 6, 2014
`
`Related U.S. Application Data
`(60) Provisional application No. 61/764,756, filed on Feb.
`14, 2013.
`
`(30)
`
`Foreign Application Priority Data
`
`Feb. 7, 2013 (AU) ................................ 2O1390O389
`Publication Classification
`
`(2006.01)
`(2006.01)
`(2006.01)
`
`(51) Int. Cl.
`C07K 6/28
`GOIN33/569
`A614.9/00
`52) U.S. C.
`(52) CPC ............. C07K 16/2866 (2013.01); A61K 49/00
`(2013.01); G0IN33/56966 (2013.01)
`USPC ... 424/9.1; 530/389.1:530/387.9; 530/387.3;
`530/391.1:536/23.53; 435/320.1; 435/252.33;
`424/172.1; 435/7.21: 435/254.2:435/334
`ABSTRACT
`(57)
`The present disclosure provides proteins comprising antigen
`binding sites of antibodies that bind to interleukin-11 (IL-11)
`receptor alpha (IL-11 RO) and uses thereof, e.g., in therapy.
`
`Lassen - Exhibit 1008, p. 1
`
`

`

`Patent Application Publication
`
`Aug. 7, 2014 Sheet 1 of 8
`
`US 2014/0219919 A1
`
`832 L3.2 DNLSPT
`TS~49
`ESQAPE
`TS“51
`ESQWPF
`
`ETQTPA
`TS*55
`TSHS7
`ETQMEL
`TS~53
`ETQQPF
`TS’SB
`DTQQPN
`T$“64
`ESQWPQ
`Com§nmw ETngF
`
`8E2 Ll ENNELN
`TS“3Q3
`VDYWVE
`TS~305
`VGIYVE
`TS*306
`VDKYVE
`T8m307
`VSMYVZ
`TS~310
`VAM?IE
`TS"311
`VSQYIE
`TS—312
`IGQYVE
`TS‘313
`VSGYUE
`TS~322
`VHHYME
`Consensus VSXYVE
`
`
`
`832 23.1 QQYDNL
`
`QQAEDQ
`TS‘E
`TE—é
`QQHEFQ
`TS—6
`EQFESQ
`TSfl7
`QQHENQ
`TS*9
`QQAEEQ
`TS“13
`QQNETQ
`Tg*lé
`QQEUNQ
`T3‘l7
`SQFESQ
`TS—QO
`QQNESQ
`TS~2 l
`QQSESQ
`TS‘ZZ
`QQFETQ
`TE? ~21 9
`QQSEEQ
`TS—32
`TQWETQ
`Cnnsenans
`QQKESQ
`
`Figure 1
`
`Lassen — Exhibit 1008, p. 2
`
`Lassen - Exhibit 1008, p. 2
`
`

`

`Patent Application Publication
`
`Aug. 7, 2014 Sheet 2 of 8
`
`US 2014/0219919 A1
`
`SWYSMT
`AWWS IA
`GWWSVT
`ERNST”
`9‘?ng 1‘1‘
`AWFS‘VM
`WRWS‘W’
`WRWSTT
`
`
`
`8E2 H1
`TS — 6 6
`TS‘SE}
`TS*71
`TS "75
`TS'~79
`TSAEZ
`TS~88
`
`WPWSI”
`TS ----- S 9
`EWYSJI.‘L1
`TSMQQ
`GWWSLT
`TS- 91
`SWWSIT
`T3” 92
`Consensus WW5 ET
`
`83.19. H3 . 3. GPGWGS
`‘“
`"
`
`
`
`a
`F?
`
`Consangus
`PEDWGX
`
`8E2 H2 VPSGGH
`TS # 9‘7
`VPWADY
`TSWIUl
`VPWGDL
`TS~103
`VPYC—QDL
`TS-“loli
`VPWGTI
`TS--l‘37
`VPWSDF
`TS~108
`VPWGTL
`TEX-“115
`VPi’iGDL
`
`Congensug VPWGDL
`
`Figure 2
`
`8E2 HS .2 WGSFDL
`T S —2 l 3
`WGQ FAV
`WGSFWF
`TEE—214
`
`WGSFWQ
`WIS—215
`TEE—218
`WGS ENE
`T’s—221
`WGSFWY
`TS~222
`WGTFAY
`TVS—224
`WGSFW’I‘
`
`Consensus WGSFWY
`
`Lassen — Exhibit 1008, p. 3
`
`Lassen - Exhibit 1008, p. 3
`
`

`

`Patent Application Publication
`
`Aug. 7, 2014 Sheet 3 of8
`
`US 2014/0219919 A1
`
`CDRZ
`r————————~
`DASNLQT
`
`
`
`DASNLQT
`DASNLQT
`DASNLQT
`DASNLQT
`DASNLQT
`DASNLQT
`DASNLQT
`DASNLQT
`DASNLQT
`DASNLQT
`DASNLQT
`DASNLQT
`DASNLQT
`DASNLQT
`DASNLQT
`DASNLQT
`DASNLQT
`DASNLQT
`DASNLQT
`DASNLQT
`DASNLQT
`DASNLQT
`DASNLQT
`DASNLQT
`DASNLQT
`DASNLQI
`DASNLQT
`DASNLQT
`DASNLQT
`
`DASNLQT
`
`8E2
`
`DIQMTQSPSSLSASVGDRVTITC
`
`INNYLN WYQQKPGKAPKLLIY
`
`CDRl
`
`DIQMTQSPSSLSASVGDRVTITC
`VDYWVE WYQQKPGKAPKLLIY
`VGIYVE WYQQKPGKAPKLLIY
`DIQMTQSPSSLSASVGDRVTITC
`DIQMTQSFSSLSASVGDRVTITC
`VDKYVE WYQQKPGKAPKLLIY
`VSMYVE WYQQKPGKAPKLLIY
`DIQMTQSPSSLSASVGDRVTITC
`DIQMTQSPSSLSASVGDRVTITC
`VAMYIE WYQQKPGKAPKLLIY
`
`DIQMTQSPSSLSASVGDRVTITC
`VSQYIE WYQQKPGKAPKLLTY
`
`DIQMTQSPSSLSASVGDRVTITC
`IGQYVE WYQQKPGKAPKLLIY
`DIQMTQSPSSLSASVGDRVTITC
`VSGYVE WYQQKPGKAPKLLIY
`
`DIQMTQSPSSLSASVGDRVTITC
`VHHYME WYQQKPGKAPKLLIY
`
`DIQMTQSPSSLSASVGDRVTITC
`INNYLN WYQQKPGKAPKLLIY
`INNYLN WYQQKPGKAPKLLIY
`
`DIQMTQSPSSLSASVGDRVTITC
`DIQMTQSPSSLSASVGDRVTITC
`INNYLN WYQQKPGKAPKLLIY
`
`DIQMIQSFSSLSASVGDRVTITC
`INNYLN WYQQKPGKAPKLLIY
`
`DIQMTQSPSSLSASVGDRVTITC
`INNYLN WYQQKPGKAPKLLIY
`DIQMTQSPSSLSASVGDRVTITC
`INNYLN WYQQKPGKAFKLLIY
`
`DIQMTQSPSSLSASVGDRVTIIC
`INNYLN WYQQKPGKAPKLLIY
`DIQMTQSPSSLSASVGDRVTIIC
`INNYLN WYQQKPGKAPKLLIY
`
`DIQMTQSPSSLSASVGDRVTITC
`INNYLN WYQQKPGKAPKLLIY
`
`INNYLN WYQQKPGKAPKLLIY
`DIQMTQSPSSLSASVGDRVTITC
`
`DIQMTQSPSSLSASVGDRVTITC
`INNYLN WYQQKPGKAPKLLIY
`
`DIQMTQSPSSLSASVGDRVTIIC
`INNYLN WYQQKPGKAPKLLIY
`
`DIQMTQSPSSLSASVGDRVTIIC
`INNYLN WYQQKPGKAPKLLIY
`DIQMTQSPSSLSASVGDRVTITC
`INNYLN WYQQKPGKAPKLLIY
`
`DIQMTQSPSSLSASVGDRVIITC
`INNYLN WYQQKPGKAPKLLIY
`
`INNYLN WYQQKPGKAPKLLIY
`DIQMTQSPSSLSASVGDRVTITC
`DIQMTQSPSSLSASVGDRVTITC
`INNYLN WYQQKPGKAPKLLIY
`
`DIQMTQSPSSLSASVGDRVTIIC
`INNYLN WYQQKPGKAPKLLIY
`DIQMTQSPSSLSASVGDRVTITC
`INNYLN WYQQKPGKAPKLLIY
`
`DIQMTQSPSSLSASVGDRVTITC
`INNYLN WYQQKPGKAPKLLIY
`
`DIQMTQSPSSLSASVGDRVTITC
` XXXXXX WYQQKPGKAPKLLIY
`INNYLN
`VDYWVE
`GI
`I
`SK M
`AM
`HQ
`
`GH
`
`Figure 3A
`
`TS~303
`18—305
`TS~306
`TS~307
`TS—3lO
`TS—3ll
`TS‘312
`TSv313
`TS~322
`TS—Z
`TS—4
`TS—S
`TS—7
`TS—9
`TSvl3
`TS—14
`TS—l7
`TSv2O
`TS-Zl
`TS—ZZ
`TS~29
`TS—32
`IS~49
`TS~51
`TS~55
`TSw57
`TSw58
`TS—63
`TSv64
`Consensus
`
`Lassen — Exhibit 1008, p. 4
`
`Lassen - Exhibit 1008, p. 4
`
`

`

`Patent Application Publication
`
`Aug. 7, 2014 Sheet 4 of 8
`
`US 2014/0219919 A1
`
`CDR3
`
`8E2
`15—303
`TS~305
`TS«306
`15—307
`TS~310
`15-311
`TS~312
`IS 313
`Ts~322
`IS—z
`13—4
`IS‘S
`TSv7
`ISuB
`13-13
`15—14
`13-17
`TS-ZC
`15—21
`15—22
`TS—29
`T8732
`TS 49
`TS~Sl
`TSvSS
`TS—57
`TS~56
`1S~53
`TS—64
`
`Consensus
`
`SVPSRESGSGSETDETET:SSLQPEDIAIYYC QQYDNL SPT FGPGTKVDIK
`GVPSRFSGSGSGIDFTFTISSLQPEDIATYYC QQYDNL SPT FGPGTKVDIK
`GVPSRESGSGSGTDEIET1SSLQEEDIATYYC QQYDNL SPT FGPGTKVDIK
`GVPSRFSGSGSGIDFTFTISSLQPEDIAIYYC QQYDNL SPT FGPGTKVDIK
`GVPSRFSGSGSGTDFIFTISSLQPEDIATYYC QQYDNL SPT FGPGTKVDIK
`GV?SRFSGSGSGTDFTPTISSLQPEDIAIYYC QQYDNL SPT FGPGTKVDIK
`
`ATYYC QQYDNL SPT FGPGTKVDIK
`GVPSRFSGSGSGIDFTFIISSLQPE
`GVPSRFSGSGSGTDFTFTISSLQPE
`IYYC QQYDNL SPT FGPGTKVDIK
`GVPSRFSGSGSGTDFTFTISSLQPE _ TYYC QQYDNL SPT FGPGTKVDIK
`
`GVPSRFSGSGSGTDFTFTISSLQEEDIATYYC QQYDNL SPT EGPGTKVDIK
`GVPSRFSGSGSGIDFTFTISSLQPEDIAIYYC QQAEDQ SPT EGPGLKVDIK
`GVPSRFSGSGSGTDFTFTISSLDPEDiATYYC QQHBFQ SET FGPGTKVDIK
`GVPSRESGSGSGIDETEIISSLQPEDIAIXYC EQFESQ SPT VGPGTKVDIK
`GVFSRFSGSGbGIDFTETlSSLQPEDTATYYC QQHENQ SPT EGPGTKVDIK
`GVPSRESGSG dIDFTFTTSSLQPEDIATYYC QQAEEQ SPT FGPGTKVDIK
`GVPSRESGSGSGTDFTFTTSSLQPEDIATYYC QQNETQ SPT PGPGTKVDIK
`GVPSRFSGSGSGTDFTFTISSLQPEDIATYYC QQHDNQ SPT FGPGTKVDIK
`GVPSRFSGSGSGTDFTFTISSLQPEDIATYYC SQFESQ SPT FGPGIKVDIK
`GVPSRFSGSGSGTDFIFTISSLQPEDIATYYC QQNESQ SET FGPGTKVDIK
`GVPSRFSGSGSGTDFTFTISSLQPEDIATYYC QQSESQ SPT FGPGTKVDIK
`GVPSRFSGSGSGTDFTFTISSLQPEDIATYYC QQEEIQ SET FGPGTKVDIK
`GVPSRFSGSGSGTDFTFTISSLQPEDIATYYC QQSEEQ SPT FGPGIKVDIK
`GVPSRFSGSGSGTDFTFTISSLQPEDIATYYC TQWElQ SET FGPGIKVDIK
`GVPSRFSGSGSGTDFTFTISELQPEDIATYYC QQYEEQ APE FGPGTKVDIK
`GVPSRFSGSGSGTDFTFTISSLQPEDIATYYC QQYESQ WPF FGFGIKVDIK
`GVPSRFSGSGSGTDFIFTISSLQPEDIATYYC QQYErQ TEA FGPGTKVDIK
`GVPSRFSGSGSGTDFIFTISSLQEEDIAIYYC OOYETQ MPL FGPGIKVDLK
`GVPSRFSGSGSGTDFTFTTSSLQPEDIATXYC QQYEIQ QEE FGPGTKVDlK
`GVPSRFSGSGSGTDFTFTISELOPEDIAIYYC QQYDTQ DEN EGPGIKVDLK
`GVPSRFSGSGSGTDFTFIISSLQPEDlATYYC QQYESQ WPQ EGPGTKVDIK
`
`GVESEESSSGSGTDEiETiSSLQPEDTATYYC XQXXXX xpx FGPGTKVDIK
`.Q YDNL s T
`iE AEDQ A E
`E S H F
`w F
`ii F S
`I A
`g
`N E
`M L
`a
`s T
`Q N
`a
`w
`c
`
`
`
`
`
`5
`SEQ ID NO:
`6
`SEQ ID NO:
`7
`SEQ I
`NO:
`8
`SEQ ID NO:
`9
`SEQ ID NO:
`10
`SEQ ID NO:
`11
`SEQ ID NO:
`12
`SEQ ID NO:
`13
`SEQ 1D NO:
`SEQ ID NO: 14
`SEQ ID NO:
`15
`SEQ TD NO:
`16
`SEQ ID NO:
`17
`SEQ ID NO:
`is
`SEQ ID NO:
`19
`SEQ ID NO: 20
`SEQ ID NO: 21
`SEQ ID NO:
`2
`SEQ ID NO: 23
`SEQ ID NO: 24
`SEQ ID NO: 25
`SEQ ID NO: 26
`SEQ ID NO:
`SEQ ID NO:
`SEQ ID NO:
`SEQ ID NO:
`SEQ ID No:
`SEQ in No:
`SEQ ID NO:
`SEQ ID NO:
`
`
`
`SEQ ID NO:
`
`
`35
`
`Figure 3A Continued
`
`Lassen — Exhibit 1008, p. 5
`
`Lassen - Exhibit 1008, p. 5
`
`

`

`Patent Application Publication
`
`Aug. 7, 2014 Sheet 5 of 8
`
`US 2014/0219919 A1
`
`CDRI
`
`CDRZ
`
`
`DLQMTQSPSSLSASVQDRVTITC QASQD Ii
`LN WYQQKPGKAPKLLTY LASNLQT
`
`DIQMTQSPSSLSASVGDRVTITC QASQD VDKYVE WYQQKPGKAFKLLIY bASNLQT
`DIQMTQSPSSLSASVCDRVTITC QASQD INNYLN WYQQKPGKAPKLLIY DASNLQT
`DIQMTQSPSSLSASVGDRVTTTC QASQ;
`IENYLN WYQQKPGKRPKLLIY DASNLQT
`DIQMTQSPSSLSASVCDRVTTTC QASEC TNNYLN WXQQKFSKAPKLLIY DASNLQT
`DIQMTQSPSSLSASVGDRVTITC QASQD INNYLN WXQQKFGKAPKLLLY DASNLOT
`DTQMTQSPSSLSASVGDEVTITC QASQU LNNYLN WYQQKPGKAPKLLIY DASNLOT
`DIQMIQSPSSLSAhVGDRVTITC
`XXXYXX WYQQKPGKAFKLLIY ASNLQT
`IDK LN
`VNN V3
`
`
`
`
`
`SEQ
`
`ID NO:
`
`CDR?
`
`FGPGTKVDIK
`FGPGTKVDIK
`FGPGTKVDIK
`FGPGTKVDIK
`FGPGTKVDIK
`FGPGTKVDIK
`FGVGTKVDIK
`FGDGTKVUTK
`
`SEQ
`SEO
`SEQ
`
`SEQ
`SEQ
`SEQ
`
`
`
`
`
`GVPSRFSGSSSGTDFTFTTSSLQPEDIATYYC
`
`GVPSRFSSSGSGTDFTFTTSSLQ EDIATYYC QQYDNL
`
`
`
`.IATY" QQAEDQ
`GVPSRFSGSGSGTDFTFTIS LQ
`
`GVVSRFSa°fl
`C QQHEFC
`TDFTFTluaLQPLDiATY:
`
`
`FTFTLSSLQYEDIATYYC
`QOHENC
`
`‘SSSGSGTUFTPTISSLOPEDIATYVC
`
`QQHDNQ
`
`
`GYPSRFSGSGSGTDFTFTISSLQPEDIAT
`{C QQYESQ
`QQXXXXYDNI‘
`AEDQ w F
`H F
`
`N5
`
`
`
`Figure SB
`
`Lassen — Exhibit 1008, p. 6
`
`BEZ
`TS~306
`TS-Z
`TS-4
`TS—7
`TS—ld
`TS-El
`
`Ccnse‘)
`
`8E2
`
`Consensus
`
`Lassen - Exhibit 1008, p. 6
`
`

`

`Patent Application Publication
`
`Aug. 7, 2014 Sheet 6 of 8
`
`US 2014/0219919 A1
`
`COR;
`
`CDRZ
`
`8E2
`
`T6-66
`T5769
`TS~71
`TS~76
`TS~79
`TS—SZ
`TS'SB
`TS~89
`TF~91
`TS—92
`TS—97
`
`
`
`Consensus
`
`
`
`EVQLLESGGG VQFGGSLRLSCAASGFTP
`
`EVQLLESGGGLVQPGGSLRLSCAASGFIF
`EVQLLESGGGLVQPGGSLR,QSAASGFTF
`
`EVQLLESGGGLVQPGGSLRLSuAASGFTF
`EVQLLESGGGLVQPGGSLRLSCAASGFTF
`EVQLLESGGGLVQPGGSLRLSCAASGFTF
`EVQLLESGGGLVOPGGSLRLSCAASGFTF
`EVQLLESGGGLVQPGGSLRLSCAASGFTF
`E
`LLESGGGLVQPGGSLRLSCAASGFTF
`
`EVQLLESGGGLVQPGGSLRLSCAASGFTF
`EVQLLESGGGLVOPGGSLRLSCAASGFTF
`EVQLLESGGGLVQPGGSLRLSCAASGFTF
`EVQLLESGGGLVQPGGSLRLSCAASGFTF
`QLLESGGGLVQPGGSLRLSCRASGFTF
`QLLESGGGLVQPGGSLRLSCAASGFTF
`QLLESGGGLVQPGGSLRLSCAASGFTF
`QLLESGGGLVQPGGSLELSCAASGET?
`VQLLESGGGLVQPGGSLRLSCAASGFTE
`
`QLLESGGGLVQPGGSLRLSCAASGFTF
`, QLLESGGGLVQPGGSLRLSCAASGFTE
`
`EVQLLESGGGLVQPGGSLRLSCAASGFIF
`
`EVQLLESGGGLVQPGGSLFLSCAASGFTF
`
`EVQLLESGGGLVQPGG
`RLSCAASUBIE
`EVQLLESGGGLVOPGGSLRLSCAASGFIF
`EVQLLESGGGLVQPGGSLRLSCAASGFTF
`EVOLLESGGGLVQPGGSLRLSCAASGF
`
`
`EVQLLESGGGLVQPGGSLRLSCAASGFI:
`EVQLLESGGGLVQPGGSLRLSCAASGFTF
`
`EVQLLESGGGLVQPGGSLRLSCAASGAIF
`EVQLLESGGGLVQPGGSLRLSCAASGFT?
`EVQLLESGGGLVQPGGSLRLSCAASGFIF
`EVQLLESGGGLVQPGGSLRLSCAAS1F
`
`
`EVQLLESGGGLVQPGGSLRLSCAASG
`EVQLLESGCCLVQPGGSLRLSCAASGFIF
`SVOLLESGGGLVQPGGSLRLSCAASGFT?
`
`m
`
`Lamar/2mmmmmmmmmmmmmmmmmmmmmiz"
`
`SaWmK
`
`
`
`
`
`Figure 3C
`
`Lassen — Exhibit 1008, p. 7
`
`
`
`IOYADSVKG
`TQYADSVKG
`TQYADSVKG
`TQYADSVKG
`IQYADSVKG
`TQYADSVKG
`TQYADSVKG
`TOYADSVKG
`TQYADSVKG
`IQYADSVVG
`TQYADSVI
`
`TQYADSVKG
`TQYADSVKG
`TQYADSVKC
`TQYADSVKG
`q
`TQYADS
`
`TQYADSVWG
`TQYADS
`
` a
`
`TQVADSV'
`TQYADSVKG
`TQYADSVKG
`TQYADSVKG
`TQYADSVKG
`TQYADSVKG
`TQYADSVKG
`TQYADSVKG
`TQYADSVKG
`TQYADSVKG
`TQYADSVKG
`TQYADSVKG
`TQYADSVKG
`TQYADSVKG
`TQYADSVKG
`TQYADSVKG
`
`TQYADSVKG
`
`VPSGCH
`VPSGGH
`VPSGGH
`VPSGGH
`VPSG .
`
`VPSGGH
`VPSGGH
`VPSGCH
`VPSGGH
`VPSGGH
`VPSGGH
`VFWADY
`VPWGDL
`VPYGDL
`VPWGTI
`VPNGDE
`VPWGTL
`VPHGDL
`VPSGGH
`VPSGGE
`PSGGH
`VPSGGE
`VPSGGH
`VPSGGH
`VPSGGE
`VPSGCH
`VPSGGH
`VPSGGE
`VPSGGH
`VPSGGE
`VPSGGE
`VPSGGH
`VPSCGE
`VPSGGE
`VPXXXX
`SGGE
`WADY
`Y TL
`H
`
`TF
`
`HhHHHHHHHH
`
`H,;
`
`u
`
` H
`><HHHHHHHHHHHHkuHHHHHHH
`
`WVRQA?GKGLEWVS
`
`WYSMT WVRQAPGKGLEWVS
`
`NWSIA
`WVRQAPGKGLEWVS
`WWSVT
`
`WVRQAPGKGLEWVS
`MSTT
`WVRQAPGKGLEWVS
`
`,WSIT
`WVRQAPGKGLEWVS
`
`IFSVT
`WVRQAPGKGLEWVS
`
`WSVT
`WVRQAPGKGLEWVS
`RWS"T
`WVPQAFGKGLEWVS
`
`RWSTT
`WVRQRPGKGLEWVS
`VWSLT
`WVRQAPGKGLEWVS
`
`IWSIT
`WVRQAPGKGLEWVS
`VYSMT
`WVRQAPGKGLEWVS
`
`IYSMT
`WVRQAPGKGLEWVS
`WYSMT
`WVRQAPGKGLEWVS
`'JYSMT
`WVRQAPGKGLEWVS
`
`JYSMT
`WVEQAPGKGLEWVS
`NYSMT
`WVRQAPGKGLEWVS
`WYSMT
`WVEQAPGKGLEWVS
`
`IYSMT
`WVRQAPGKGLEWVS
`WYSMT
`WVRQAPGKGLEWVS
`WISMT
`WVRQAPGKGLEWVS
`
`WYSMT
`WVRQAPGKGLEWVS
`VYSMT
`WVROAPGKGLEWVS
`WYSMT
`WVRQAPGKGLEWVS
`JYSMT
`WVRQAPCKCLEWVS
`WYSMT
`WVRQAPGKGLEWVS
`JYSMT
`WVRQAPGKGLEWVS
`WYSMT
`WVRQAPGKGLEWVS
`WYSMT
`WVEQAPGKGLEWVS
`WYSMT
`
`WVRQAPGKGLEWV
`XSMT
`WVRQAEGKGLEWVS
`WYSMT
`
`WVRQAPGKGLEWV‘
`YSMT
`WVRQAPGKGLEMVS
`WYSMT
`hVRQAPGKGLEWVS
`XSXX
`WY MT
`
`Lassen - Exhibit 1008, p. 7
`
`

`

`Patent Application Publication
`
`Aug. 7, 2014 Sheet 7 of8
`
`US 2014/0219919 A1
`
`CD83
`NO'
`NO:
`NO:
`NO
`NC
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`
`Figure 3C Continued
`
`Lassen — Exhibit 1008, p. 8
`
`VLNHE
`
` 29
`
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`
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`TS-l35
`TS—136
`‘
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`1“ 143
`
`TS*151
`TS~156
`TE~213
`T372l4
`TSr2WS
`TS—218
`TS—ZZl
`TS~222
`TS~224
`Consensus
`
`EFTISRDNSKNTLYLQMNSLRAEDTAVYYCAK
`RFTTSRDNSKNTLYLQMNSLRBVDVA”YYCAK
`RFTISRDNSKNTLYLQMNSLRP
`YYCRK
`
`RFIISRDNSKNTIYLQMNSLRAED AVYYCAK
`RPTISRDNSKNTLYLQMNSLRAEDTAVYYCAK
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`RFTT5RDUSKNTLYLQMNSLRAEDTAVYYCAK
`RF:ISRDNSKNTLYLQMNELEAEDTAVXECAK
`EFTISRDNSKNTLYLQMNSLRAEDTAVYYCAK
`KFTISRDNS NTLYLQMNSLRAEDTAVYYCAK
`
`RFTISRDN
`NSLRAEDTAVYYCAK
`RFTISRDN”iNTLYLQMNSLRAEDIAVYYCAK
`RFTISRDNS NTLYIQMNSLRAEDTAVYYCAK
`RFTISRDNSANTLYLQMNSLRAEDIAVYYCAK
`RFTISRDNSKNTLYLOMNSLRAEDIAVYYCAK
`RFTTSRDNSiNTLYLQMNSLRAEDTAVYYCAK
`REIISRDNSKNTLYDQMNGLBEBDIAVXYCAK
`RETISRDNSKNTLYLCMNS RAEDTRVYYCRV
`RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAK
`
`R TISRDNSKNTLYLCMNSLRAEDTAVYYCAK
`R:TlERDNSKNTLYLQMNSLRAEDTAVYYCAK
`
`RETISRDNSKNTLYLQMNS RAEDlAVYYCAK
`RETISRDNSKNTLYLQMNSLRAEDTRVYYC3?
`RFTISRDNSKNTLYLQMNSLRAEDTAVYYF
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`
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`
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`
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`RFTISRDNSKNT ILQMNSLRAEDTAVY’
`.
`
`
`RFTl5RDNSKNTLYLQMNSLRABDTAVYYCAS
`
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`RFTISRDNSKNTuYLQMNSLRAEDTAVYYVAK
`RFTISRDNSKNT ILQMNSLRREDTAVYYF
`.
`
`
`RFTISRDNSKNTLYLQMNSLRAEDIAVYYCAK
`
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`
`acr'wzm
`
`_ WGREILVTVSS
`
`GPS
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`
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`GPG
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`WGFGILVIVSS
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`GPG
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`WGSFDL
`GPG
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`WGSFDL
`CPS
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`SS
`
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`WGRGTLVTVSS
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`GPG
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`WGRGTLV”VSS
`EED
`WGMFEL
`WGQGT’
`
`PVD
`WGPFEL
`
`WGRGTI‘
`‘.
`
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`FED
`WGRGTLVIV
`PLD
`WGLFDL
`WGRGTL
`FLU
`WGRFrL
`
`WGRGTI
`PND
`WGRGTL
`wc FLL
`PHD
`WGRGTLV
`WULFDL
`PHD
`WGRFDL
`WGRGTL
`WGRFDL
`
`FED
`WGRGTL‘
`GFG
`WGRGTL
`WGQFAV
`GFG
`wcstr
`WGRGT'LV’r
`WGRGTLVTV
`GFG
`WGSFWQ
`
`GPG
`WGSFWE
`WGRGTL‘
`GPG
`WGSFWY
`WGRGTLV;
`
`WGRGTL
`GFG
`WGTEAZ
`WGSFMT
`GPG
`WGRGTLVLVSS
`
`WGXFXX
`XXX
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`GFG
`DL
`AV
`PED
`WF
`
`
`
`QEYT
`
`Lassen - Exhibit 1008, p. 8
`
`

`

`Patent Application Publication
`
`Aug. 7, 2014 Sheet 8 of 8
`
`US 2014/0219919 A1
`
`2 I
`
`QYADSVKG
`TQYADSVKG
`TQYADSVKG
`TQYADSVKG
`TQYADQVVG
`TQYADSVKG
`
`’1,
`
`CDR
`VPSGGH
`VFWGDL
`VPWGTL
`VPSGGH
`VPSGGH
`VPXGXX
`5 GH
`W DL
`
`WVRQAPGKGLEWVS
`WVRQATGKGLEWVS
`WVRQAPGKGLEWVS
`WVRQAPGKGLEWVS
`WVRQAPGKGLEWVS
`WVRQAPGKGLEWVS
`
`
`
`CDRI
`NYSMT
`WYSMT
`IIYSMT
`WYSMT
`JYSMI
`flYSMT
`
`S mwmm
`
`EVQLLESGGGLVQPGGSLRLSCAASGFTF
`
`EVQLLESGGGLVQPGGSLRLSCAASG
`EVQLLESGGGLVQPGGSLRLSCAASGA
` m
`BVQLLESGGGIVQPGGSLRLSCAASGF
`EVQLLESGGGLVQPGGSLRLSCABSG.M
`EVQLLESCCCLVQPGGSLRLSCAASGETF
`
`832
`TS—lDl
`TS—lOB
`:37134
`TS~136
`Consensus
`
`
`GPG
`GPG
`GPG
`PED
`PLD
`XXX
`GPG
`PED
`L
`
`
`
`ID NO: 37
`10 NO:
`49
`ID NO:
`33
`ID NO:
`5
`ID NO:
`5
`ID NO:
`72
`
`Lassen — Exhibit 1008, p. 9
`
`
`WGSFDL WGRGTLVTVSS
`
`
`WGDGTTVTV
`WGSFDL
`WGSFDI
`WG:
`LVTVSS
`
`
`WGLFDL
`WGRGTLVTVSS
`WGRFDL
`WGRGTLVTVSS
`
`WCXFD;
`WGRGTLVTVSS
`
`
`SLR
`
`IfigurEBD
`
`1a
`TS
`IS
`
`IS
`
`Consensus
`
`RFIISRDNSKNELYLQMNSLRAEDTAVYYCAK
`RETISRDNSKNT
`LYLQMNSLRAEDTAVYYCAK
`RFTISRDNSKN”LYLQMNSLRAEDEAVYYCAK
`
`AVYYCAK
`RFTISRDNSKNTLYLQMNSDRAL
`DTAVYYCAK
`RVTiSHDNSKNTLYLQMNSLR
`
`RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAK
`
`
`
`Lassen - Exhibit 1008, p. 9
`
`

`

`US 2014/02199 19 A1
`
`Aug. 7, 2014
`
`IL-11 RBINDING PROTEINS AND USES
`THEREOF
`
`RELATED APPLICATION DATA
`0001. The present application claims priority from Aus
`tralian Patent Application No. 2013900389 entitled “IL-11R
`binding proteins and uses thereof filed on 7 Feb. 2013 and
`from U.S. Patent Application No. 61/764,756 entitled “IL
`11 Rbinding proteins and uses thereof filed on 14 Feb. 2013.
`The entire contents of those applications are hereby incorpo
`rated by reference.
`
`SEQUENCE LISTING
`0002 The Sequence Listing in the ASCII text file, named
`as P29799 SequenceListingProvisional.txt of 164 KB, cre
`ated on Feb. 14, 2013, and submitted to the United States
`Patent and Trademark Office via EFS-Web, is incorporated
`herein by reference.
`
`FIELD
`0003. The present disclosure relates to proteins compris
`ing antigen binding sites of antibodies that bind to interleu
`kin-11 (IL-11) receptor alpha (IL-11 RC.) and uses thereof,
`e.g., in therapy.
`
`BACKGROUND
`0004 IL-11 is a member of the IL-6 cytokine family which
`also comprises IL-27, IL-31, leukemia inhibitory factor
`(LIF), oncostatin M (OSM) and ciliary neurotrophic factor
`(CNTF) amongst others. IL-6 family cytokines induce signal
`transduction via a common signal-transducing receptor
`B-subunit, gp130 and a specific receptor C-Subunit. In the
`case of IL-11, binding of this cytokine to its specific receptor
`C.-subunit, IL-11 RC, induces gp130 homodimerization.
`Dimerization of gp130 activates the JAK/STAT signaling
`pathway and leads to the activation of signal transducer and
`activator of transcription (STAT) 3 (STAT3) and to a lesser
`extent, STAT1.
`0005 IL-11 signaling is known to play a role in hemato
`poiesis, immune response, inflammation, adipogenesis,
`osteoclastogenesis, neurogenesis, megakaryocyte maturation
`and platelet production. IL-11 is used clinically or is in devel
`opment for treating a variety of conditions, e.g., chemo
`therapy-induced thrombocytopenia, and various inflamma
`tory disorders including arthritis, inflammatory bowel
`disease, radiation-induced lung damage, sepsis and psoriasis.
`However, clinical use of IL-11 has been restricted due to
`reports of serious adverse events including edema. Moreover,
`IL-11 has been shown to have deleterious effects in various
`conditions.
`0006 For example, IL-11 has been found to act as an
`inhibitor of bone formation, and is critical for osteoclast
`formation and activity and bone resorption. Thus, blocking
`the activity of IL-11 has been proposed as a treatment for
`osteoporosis and for preventing bone resorption/promoting
`bone formation in other conditions such as metastatic bone
`cancer, myeloma, Paget’s disease of bone, and bone fracture
`and healing.
`0007 IL-11 signaling has been implicated as having a
`pathogenic role during the early phase of tuberculosis. Block
`ing IL-11 with an anti-IL-11 antibody was shown to diminish
`histopathology and neutrophilic infiltration of the lung tissue
`in mice infected with Mycobacterium tuberculosis.
`
`0008 Antagonism of IL-11 has also been proposed as a
`method of treating Th2-mediated disorders including asthma,
`chronic obstructive pulmonary disease (COPD), rhinitis,
`allergies and atopic dermatitis. In this regard, blocking IL-11
`signaling using a mutant form of IL-11 that does not induce
`signal transduction was shown to be of therapeutic benefit in
`a mouse model of asthma.
`0009 IL-11 and/or IL-11 RC. is overexpressed in liver can
`cer, pancreatic cancer, gastric cancer, osteosarcoma, endome
`trial cancer and ovarian cancer. Moreover, as discussed
`above, IL-11 induced gp130 dimerization leads to activation
`of STAT3, which induces expression of genes associated with
`angiogenesis (e.g. VEGF), cell cycle progression (e.g. cylin
`D1) and cell survival (e.g. Bcl-XL, survival). Persistent
`STAT3 activity appears to be associated with hematologic
`malignancies and tumors of epithelial origin. Excessive
`STAT3 activation promotes the growth and survival of gastric
`cells, is associated with increased gastric angiogenesis and
`leads to gastric tumorigenesis in mice. However, gastric
`inflammation, hyperplasia and tumor formation are Sup
`pressed in IL-11 unresponsive mice or in mice treated with a
`non-signaling mutant of IL-11.
`0010 IL-11 is also involved in other biological processes,
`Such as, inhibition of adipogenesis, induction of cachexia
`(e.g., cancer cachexia), induction of a febrile response, modu
`lation of extracellular matrix metabolism, stimulation of
`acute-phase reactants and embryo implantation.
`0011. It will be apparent to the skilled artisan from the
`foregoing that reagents that neutralize IL-11 signaling are
`desirable for their potential to provide a therapeutic benefit in
`any of a number of diverse conditions. Reagents that bind to
`the IL-11 RC. are also desirable since they have the advantage
`of being capable of specifically targeting cells in vivo as
`opposed to needing to bind to and neutralize soluble IL-11
`throughout a subject.
`0012 Despite this desirability, many reagents (e.g., anti
`bodies) that bind to IL-11 RC. do not neutralize IL-11 signal
`ing. For example, Blanc et al (Journal of Immunological
`Methods 241: 43-59, 2000) described a panel of 14 mouse
`monoclonal antibodies raised against human IL-11 RC, but
`none of them were capable of inhibiting IL-11-induced pro
`liferation of BaF3/gp130/IL-11R cells, indicating that the
`antibodies do not neutralize IL-11 signaling. Commercially
`available anti-IL-11 RC. antibodies, e.g., 4D12 available from
`Santa Cruz, Biotechnology, Inc., also do not neutralize IL-11
`signaling.
`
`SUMMARY
`0013. In producing the present invention, the inventors
`sought to produce reagents (e.g., antibodies and proteins
`comprising antigen binding domains thereof) that bind to
`IL-11 RC. and neutralize IL-11 signaling. The inventors pro
`duced a series of antibodies having Such activity, some of
`which potently neutralize IL-11 signaling, e.g., prevent pro
`liferation of IL-11-dependent BaF3 cell proliferation. These
`antibodies were shown to be cross-reactive with human
`IL-11RC. (hIL-11RC.) and cynomolgus monkey IL-11 RC. (cy
`noIL-11 RO), meaning that they may be used in primate mod
`els of human disease. The antibodies were also found to bind
`to overlapping epitopes. The inventors then affinity matured
`one of these antibodies and produced a series of additional
`antibodies having additional desirable properties, e.g., neu
`tralization of IL-11 signaling and/or improved affinity and/or
`
`Lassen - Exhibit 1008, p. 10
`
`

`

`US 2014/02199 19 A1
`
`Aug. 7, 2014
`
`sequences similar to human germline (e.g., having a reduced
`likelihood of inducing an immune response when adminis
`tered to a human).
`0014 Based on the foregoing, it will be apparent to the
`skilled artisan that the inventors have produced a protein
`comprising an antigen binding domain of an antibody, the
`antigen binding domain capable of binding to or specifically
`binding to IL-11RC. and neutralizing IL-11 signaling.
`0015. In one example, the present disclosure provides an
`IL-11RC.-binding protein comprising an antigen binding
`domain of an antibody, the antigenbinding domain binds to or
`specifically binds to IL-11 RC. and neutralizes IL-11 signal
`ing, wherein the antigenbinding domain is capable of binding
`to hiL-11RC. and cynoIL-11 RC.
`0016. In one example, the IL-11 RC-binding protein neu
`tralizes human IL-11 (hIL-11) and/or cynomolgus monkey
`IL-11 (cynoL-11) signaling.
`0017. The present disclosure additionally or alternatively
`provides an IL-11 RC.-binding protein comprising an antigen
`binding domain of an antibody, wherein the antigen binding
`domain binds to or specifically binds to IL-11 RC. and neu
`tralizes IL-11 signaling and the protein inhibits IL-11 (e.g.,
`hIL-11 or cynolL-11)-mediated proliferation of BaF3 cells
`expressing IL-11 RC. and gp130 with an ICso of 10 ug/ml or
`less. In one example, the ICso is 5ug/ml or less. For example,
`the ICs is 4 g/ml or less or 3.5 g/ml or less. In one example,
`the ICso is 3 ug/ml or less or 2 ug/ml or less. For example, the
`ICs is 1 g/ml or less. For example, the ICs is 0.9 g/ml or
`less or 0.8 g/ml or less or 0.7 g/ml. In one example, the ICso
`is 0.7 ug/ml or less. In one example, relating to each of the
`foregoing examples, the ICso can be 10 pg/ml or more or 10
`ng/ml or more.
`0018. In one example, the IL-11 RC-binding protein inhib
`its IL-11 (e.g., hIL-11 or cynolL-11)-mediated proliferation
`of BaF3 cells expressing IL-11 RC. and gp130 with an ICso at
`least about 1.5 fold greater than antibody 8E2 (comprising a
`heavy chain comprising a sequence set forth in SEQID NO:
`83 and a light chain comprising a sequence set forth in SEQ
`ID NO: 84). In one example, the ICs is at least about 2 fold
`greater or at least about 2.5 fold greater or at least about 3 fold
`greater than antibody 8E2.
`0019. In one example, the ICso is determined by culturing
`BaF3 cells expressing IL-11RC. and gp130(e.g., genetically
`modified to express IL-11 RC. and/or gp130) (e.g., about
`1x10" cells) in the presence of from about 0.5 ng/mL hIL-11
`to about 5 ng/mL hIL-11 (e.g., in the presence of about 0.5
`ng/mL hIL-11 or about 5 ng/mL hIL-11) for about 48 hours.
`In one example, proliferation is determined by measuring
`incorporation of 3H-thymidine into DNA during the last 6
`hours of culture. In assays performed to determine neutral
`ization of cynolL-11, the cells can be cultured in the presence
`offrom about 0.5 ng/mL cynoIL-11 to about 5 ng/mL cynoL
`11 (e.g., in the presence of about 0.5 ng/mL cynoL-11 or
`about 5 ng/mL cynoIL-11).
`0020. The present disclosure additionally or alternatively
`provides an IL-11 RC.-binding protein comprising an antigen
`binding domain of an antibody, wherein the antigen binding
`domain binds to or specifically binds to IL-11 RC. and neu
`tralizes IL-11 signaling and the level of binding of the
`IL-11RC.-binding protein to a polypeptide of SEQID NO: 86
`is lower than the level of binding of the IL-11 RC-binding to a
`polypeptide of SEQID NO:3 and/or 85.
`0021. The present disclosure additionally or alternatively
`provides an IL-11 RC.-binding protein comprising an antigen
`
`binding domain of an antibody, wherein the antigen binding
`domain binds to or specifically binds to IL-11 RC. and neu
`tralizes IL-11 signaling and the level of binding of the
`IL-11RC.-binding protein to a polypeptide of SEQID NO: 89
`is lower than the level of binding of the IL-11 RC-binding to a
`polypeptide of SEQID NO:3 and/or 85.
`0022. In one example, the level of binding is determined
`by Western Blotting and/or by fluorescence-activated cell
`sorting (FACS) of cells expressing the polypeptide.
`0023. In one example, the level of binding of the IL-11 RC.-
`binding protein to the polypeptide of SEQID NO: 86 or 89 is
`reduced by at least about 10 fold or 20 fold or 50 fold or 100
`fold or 150 fold or 200 fold compared to the binding of the
`IL-11RC.-binding protein to the polypeptide of SEQID NO:
`3 and/or 85.
`0024. In one example, the IL-11RC.-binding protein does
`not detectably bind to the polypeptide of SEQID NO: 86 or
`89.
`0025. In one example, the IL-11RC.-binding protein binds
`to a polypeptide of SEQID NO: 87 or 88. For example, the
`level of binding of the IL-11 RC.-binding protein binds to a
`polypeptide of SEQID NO: 87 or 88 is similar to or about the
`same as (e.g., within about 20% or 15% or 10% or 5%) of the
`level of binding to the polypeptide of SEQID NO: 3 and/or
`85.
`0026. The present disclosure additionally or alternatively
`provides an IL-11 RC-binding protein comprising an antigen
`binding domain of an antibody, wherein the antigen binding
`domain binds to or specifically binds to IL-11 RC, and neu
`tralizes IL-11 signaling and the antigenbinding domain binds
`to an epitope comprising residues within the first fibronectin
`III domain of IL-11 RC.
`0027. In one example, the epitope comprises residues
`within the immunoglobulin-like domain and the first
`fibronectin III domain of IL-11RC.
`0028. In one example, the epitope comprises residues
`between amino acids 111-215 of SEQID NO: 1.
`0029. In one example, the epitope comprises residues
`between amino acids 1-215 of SEQID NO: 1.
`0030 The present disclosure additionally or alternatively
`provides an IL-11 RC-binding protein comprising an antigen
`binding domain of an antibody, wherein the antigen binding
`domain binds to or specifically binds to IL-11 RC. and neu
`tralizes IL-11 signaling and wherein the protein competi
`tively inhibits binding of antibody 8E2 (comprising a V
`comprising a sequence set forth in SEQID NO:37 and a V,
`comprising a sequence set forth in SEQ ID NO: 5) to hiL
`11RC. and/or to a polypeptide of SEQID NO:3 and/or 85.
`0031. The present disclosure additionally or alternatively
`provides an IL-11 RC-binding protein comprising an antigen
`binding domain of an antibody, wherein the antigen binding
`domain binds to or specifically binds to IL-11 RC. and neu
`tralizes IL-11 signaling and wherein the protein competi
`tively inhibits binding of antibody 8E4 (comprising a V
`comprising a sequence set forth in SEQID NO: 74 and a V,
`comprising a sequence set forth in SEQID NO: 73) to hiL
`11RC. and/or to a polypeptide of SEQID NO:3 and/or 85.
`0032. The present disclosure additionally or alternatively
`provides an IL-11 RC-binding protein comprising an antigen
`binding domain of an antibody, wherein the antigen binding
`domain binds to or specifically binds to IL-11 RC. and neu
`tralizes IL-11 signaling and wherein the protein competi
`tively inhibits binding of antibody 8D10 (comprising a V
`comprising a sequence set forth in SEQID NO: 76 and a V,
`
`Lassen - Exhibit 1008, p. 11
`
`

`

`US 2014/02199 19 A1
`
`Aug. 7, 2014
`
`comprising a sequence set forth in SEQID NO: 75) to hIL
`11 RC. and/or to a polypeptide of SEQID NO:3 and/or 85.
`0033. The present disclosure additionally or alternatively
`provides an IL-11 RC.-binding protein comprising an antigen
`binding domain of an antibody, wherein the antigen binding
`domain binds to or specifically binds to IL-11 RC. and neu
`tralizes IL-11 signaling and wherein the protein competi
`tively inhibits binding of antibody 8E2 (comprising a heavy
`chain comprising a V comprising a sequence set forth in
`SEQID NO:37 and a human IgG4 constant region and a light
`chain comprising a V, comprising a sequence set forth in
`SEQ ID NO: 5 and a human light chain constant region) to
`hIL-11 RC. and/or to a polypeptide of SEQID NO: 3 and/or
`85.
`0034. The present disclosure additionally or alternatively
`provides an IL-11 RC.-binding protein comprising an antigen
`binding domain of an antibody, wherein the antigen binding
`domain binds to or specifically binds to IL-11 RC. and neu
`tralizes IL-11 signaling and wherein the protein competi
`tively inhibits binding of antibody 8E4 (comprising a heavy
`chain comprising a V comprising a sequence set forth in
`SEQID NO: 74 and a human IgG4 constant region and a light
`chain comprising a V comprising a sequence set forth in
`SEQID NO: 73 and a human light chain constant region) to
`hIL-11 RC. and/or to a polypeptide of SEQID NO: 3 and/or
`85.
`0035. The present disclosure additionally or alternatively
`provides an IL-11 RC.-binding protein comprising an antigen
`binding domain of an antibody, wherein the antigen binding
`domain binds to or specifically binds to IL-11 RC. and neu
`tralizes IL-11 signaling and wherein the protein competi
`tively inhibits binding of antibody 8D10 (comprising a heavy
`chain comprising a V comprising a sequence set forth in
`SEQID NO: 76 and a human IgG4 constant region and a light
`chain comprising a V comprising a sequence set forth in
`SEQID NO: 75 and a human light chain constant region) to
`hIL-11 RC. and/or to a polypeptide of SEQID NO: 3 and/or
`85.
`0036. The present disclosure additionally or alternatively
`provides an IL-11 RC.-binding protein comprising an antigen
`binding domain of an antibody, wherein the antigen binding
`domain binds to or specifically binds to IL-11 RC. and neu
`tralizes IL-11 signaling and wherein the protein competi
`tively inhibits binding of antibody 8E2 (comprising a heavy
`chain comprising a sequence set forth in SEQID NO: 83 and
`a light chain comprising a sequence set forth in SEQID NO:
`84) to hiL-11RC. and/or to a polypeptide of SEQ ID NO: 3
`and/or 85.
`0037. The present disclosure additionally or alternatively
`provides an IL-11 RC.-binding protein comprising an antigen
`binding domain of an antibody, wherein the antigen binding
`domain binds to or specifically binds to IL-11 RC. and neu
`tralizes IL-11 signaling and wherein the protein competi
`tively inhibits binding of antibody 8E4 (comprising a heavy
`chain comprising a sequence set forth in SEQID NO: 92 and
`a light chain comprising a sequence set forth in SEQID NO:
`91) to hiL-11RC. and/or to a polypeptide of SEQ ID NO: 3
`and/or 85.
`0038. The present disclosure additionally or alternatively
`provides an IL-11 RC.-binding protein comprising an antigen
`binding domain of an antibody, wherein the antigen binding
`domain binds to or specifically binds to IL-11 RC. and neu
`tralizes IL-11 signaling and wherein the protein competi
`tively inhibits binding of antibody 8D10 (comprising a
`
`heavy chain comprising a sequence set forth in SEQID NO:
`94 and a light chain comprising a sequence set forth in SEQ
`ID NO: 93) to hiL-11RC. and/or to a polypeptide of SEQID
`NO:3 and/or 85.
`0039. The present disclosure additionally or alternatively
`provides an IL-11 RC-binding protein comprisin