Specific binding agents of human angiopoietin-2
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Abstract
Disclosed are peptides that bind to Ang-2. Also disclosed are peptibodies comprising the peptides, methods of making such peptides and peptibodies, and methods of treatment using such peptides and peptibodies.
55 Citations
109 Claims
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1-24. -24. (canceled)
- 31. A polypeptide capable of binding Ang-2 comprising an amino acid sequence of the formula:
- 34. A polypeptide capable of binding Ang-2 comprising an amino acid sequence of the formula:
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36. A polypeptide comprising at least one amino acid sequence selected from the group consisting of SEQ ID NO:
- 6, and SEQ ID NO;
119 to SEQ ID NO;
142, inclusive, wherein said polypeptide is capable of binding to Ang-2, and physiologically acceptable salts thereof;
- 6, and SEQ ID NO;
- 55. A polypeptide capable of binding Ang-2 comprising an amino acid sequence of the formula:
- 59. A polypeptide capable of binding Ang-2 comprising an amino acid sequence of the formula:
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61. A polypeptide comprising at least one amino acid sequence selected from the group consisting of SEQ ID NO:
- 3, and SEQ ID NO;
143 to SEQ ID NO;
148, inclusive, wherein said polypeptide is capable of binding to Ang-2, and physiologically acceptable salts thereof;
- 3, and SEQ ID NO;
- 80. A polypeptide capable of binding Ang-2 comprising an amino acid sequence of the formula:
- 85. A polypeptide capable of binding Ang-2 comprising an amino acid sequence of the formula:
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87. A polypeptide comprising at least one amino acid sequence selected from the group consisting of SEQ ID NO:
- 5, and SEQ ID NO;
149 to SEQ ID NO;
157, inclusive, wherein said polypeptide is capable of binding to Ang-2, and physiologically acceptable salts thereof;
- 5, and SEQ ID NO;
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106. A polypeptide according to any of SEQ ID NO:
- 1, SEQ ID NO;
2, SEQ ID NO;
3, or SEQ ID NO;
4, or a variant thereof.
- 1, SEQ ID NO;
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107. A polypeptide according to any of SEQ ID NO:
- 5, SEQ ID NO;
6, or SEQ ID NO;
7, or a variant thereof.
- 5, SEQ ID NO;
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108. A composition of matter having the formula:
(X1)q—
F1—
(X2)rand multimers thereof, wherein;
F1 is a vehicle;
X1 and X2 are each independently selected from -(L1)s-P1;
-(L1)s-P1-(L2)t-P2;
-(L1)s-P1-(L2)t-P2-(L3)u-P3; and
-(L1)s-P1-(L2)t-P2-(L3)u-P3-(L4)v-P4;
wherein one or more of P1, P2, P3, and P4 each independently comprise a polypeptide selected from the group consisting of;
(a) the amino acid sequence WDPWT (SEQ ID NO;
65), wherein said polypeptide is from 5 to 50 amino acids in length;
(b) the amino acid sequence WDPWTC (SEQ ID NO;
66);
(c) the amino acid sequence Cz2WDPWT (SEQ ID NO;
67), wherein Z2 is an acidic or neutral polar amino acid residue;
(d) the amino acid sequence Cz2WDPWTC (SEQ ID NO;
68), wherein Z2 is an acidic or neutral polar amino acid residue;
(e) the amino acid sequence Pc2Dc4Lc6c7c8LY (SEQ ID NO;
71) wherein c2 is a neutral hydrophobic amino acid residue;
c4 is a A, D, or E;
c6 is an acidic amino acid residue;
c7 is an amino acid residue; and
C8 is a neutral hydrophobic, neutral polar, or basic amino acid residue;
(f) the amino acid sequence RPe3e4e5e6e7G (SEQ ID NO;
73) wherein e3 is a neutral polar amino acid residue;
e4 is an acidic amino acid residue;
e5 is a neutral polar or an acidic amino acid residue;
e6 is a neutral hydrophobic amino acid residue; and
e7 is a neutral hydrophobic amino acid residue;
(g) the amino acid sequence Cg2Gg4g5DPFTg10GCg13 (SEQ ID NO;
75) wherein g2 is an acidic amino acid residue;
g4 is a neutral hydrophobic amino acid residue;
g5 is a neutral polar or an acidic amino acid residue;
g10 is a neutral hydrophobic or neutral polar amino acid residue; and
g13 is an acidic residue;
(h) A polypeptide of SEQ ID NO;
1;
(i) A polypeptide of SEQ ID NO;
2; and
(j) A polypeptide of SEQ ID NO;
7;
L1, L2, L3, and L4 are each independently linkers; and
q, r, s, t, u, and v are each independently 0 or 1, provided that at least one of q and r is 1;
and physiologically acceptable salts thereof.
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109. (canceled)
Specification