C - Chemistry – Metallurgy – 12 – N
Patent
C - Chemistry, Metallurgy
12
N
C12N 15/28 (2006.01) A61K 38/19 (2006.01) C07K 1/04 (2006.01) C07K 7/06 (2006.01) C07K 7/08 (2006.01) C07K 14/00 (2006.01) C07K 14/47 (2006.01) C07K 14/52 (2006.01) C07K 14/525 (2006.01) C07K 19/00 (2006.01) C12N 5/10 (2006.01) C12N 15/10 (2006.01) C12N 15/13 (2006.01) C12N 15/63 (2006.01) A61K 38/00 (2006.01)
Patent
CA 2446189
The present invention concerns therapeutic agents that modulate the activity of TALL-1. In accordance with the present invention, modulators of TALL-1 may comprise an amino acid sequence Dz2~Lz4~ wherein z2~ is an amino acid residue and z4~ is threonyl or isoleucyl. Exemplary molecules comprise a sequence of the formulae a1~a2~a3~CDa6~La8~a9~a10~Ca12~a13~a14~ (SEQ.ID.NO:100), b1~b2~b3~Cb5~b6~Db8~Lb10~b11~b12~b13~b14~Cb16~b17~b18~ (SEQ.ID.NO:104) c1~c2~c3~Cc5~Dc7~Lc9~c10~c11~c12~c13~c14~Cc16~c17~c18~ (SEQ.ID.NO:105) d1~d2~d3~Cd5~d6~d7~WDd10~Ld13~d14~d15~Cd16~d17~d18~ (SEQ.ID.NO:106) e1~e2~e3~Ce5~e6~e7~De9~Le11~Ke13~Ce15~e16~e17~e18~ (SEQ.ID.NO:107) f1~f2~f3~Kf5~Df7~Lf9~f10~Qf12~f13~f14~ (SEQ.ID NO:109) wherein the substituents are as defined in the specification. The invention further comprises compositions of matter of the formula (X1~)~a-V1~-(X2~)~b wherein V1~ is a vehicle that is covalently attached to one or more of the above TALL- 1 modulating compositions of matter. The vehicle and the TALL-1 modulating composition of matter may be linked through the N- or C-terminus of the TALL-1 modulating portion. The preferred vehicle is an Fc domain, and the preferred Fc domain is an IgG Fc domain.
L'invention concerne des agents thérapeutiques qui modulent l'activité de TALL-1. Selon l'invention, les modulateurs de TALL-1 peuvent comprendre une séquence d'acides aminés Dz<2>Lz<4> dans laquelle z<2> représente un résidu d'acides aminés et z<4> représente thréonyle ou isoleucyle. Des molécules modèles comprennent une séquence de la formule a<1>a<2>a<3>CDa<6>La<8>a<9>a<10>Ca<12>a<13>a<14> (SEQ.ID.NO:100), b<1>b<2>b<3>Cb<5>b<6>Db<8>Lb<10>b<11>b<12>b<13>b<14>Cb<16>b<17>b<18> (SEQ.ID.NO:104) c<1>c<2>c<3>Cc<5>Dc<7>Lc<9>c<10>c<11>c<12>c<13>c<14>Cc<16>c<17>c<18> (SEQ.ID.NO:105) d<1>d<2>d<3>Cd<5>d<6>d<7>WDd<10>Ld<13>d<14>d<15>Cd<16>d<17>d<18> (SEQ.ID.NO:106) e<1>e<2>e<3>Ce<5>e<6>e<7>De<9>Le<11>Ke<13>Ce<15>e<16>e<17>e<18> (SEQ.ID.NO:107) f<1>f<2>f<3>Kf<5>Df<7>Lf<9>f<10>Qf<12>f<13>f<14> (SEQ.ID NO:109), dans laquelle les substituants sont tels que définis dans le descriptif. L'invention concerne par ailleurs des compositions de matière de formule (X<1>)a-V<1>-(X<2>)b, dans laquelle V<1> est un excipient fixé par covalence à un ou plusieurs des composés de modulation de TALL-1 précités. L'excipient et la composition de modulation de TALL-1 de ladite matière peuvent être liés par N terminal ou C terminal de la portion de modulation de TALL-1. L'excipient préféré est un domaine Fc, et le domaine Fc préféré est un domaine IgG Fc.
Hsu Hailing
Min Hosung
Xiong Fei
Amgen Inc.
Gowling Lafleur Henderson Llp
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