Ligands that have binding specificity for VEGF and/or EGFR and methods of use therefor
First Claim
Patent Images
1. A ligand that has binding specificity for vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR), comprising at least one protein moiety that has a binding site with binding specificity for VEGF and at least one protein moiety that has a binding site with binding specificity for EGFR.
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Accused Products
Abstract
Disclosed are ligands that have binding specificity for vascular endothelial growth factor (VEGF), for epidermal growth factor receptor (EGFR), or for VEGF and EGFR. Also disclosed are methods of using these ligands. In particular, the use of these ligands for cancer therapy is described.
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Citations
115 Claims
- 1. A ligand that has binding specificity for vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR), comprising at least one protein moiety that has a binding site with binding specificity for VEGF and at least one protein moiety that has a binding site with binding specificity for EGFR.
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8. A ligand that has binding specificity for vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR), comprising at least one immunoglobulin single variable domain with binding specificity for VEGF and at least one immunoglobulin single variable domain with binding specificity for EGFR, wherein
each said immunoglobulin single variable domain with binding specificity for VEGF competes for binding to VEGF with an anti-VEGF domain antibody (dAb) selected from the group consisting of TAR15-6 (SEQ ID NO: - 117), TAR15-8 (SEQ ID NO;
119), and TAR15-26 (SEQ ID NO;
123). - View Dependent Claims (9)
- 117), TAR15-8 (SEQ ID NO;
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16-21. -21. (canceled)
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26. A ligand that has binding specificity for vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR), comprising at least one immunoglobulin single variable domain with binding specificity for VEGF and at least one immunoglobulin single variable domain with binding specificity for EGFR, wherein
each said immunoglobulin single variable domain with binding specificity for VEGF competes for binding to VEGF with an anti-VEGF domain antibody (dAb) selected from the group consisting of TAR15-6 (SEQ ID NO: - 117), TAR15-8 (SEQ ID NO;
119), and TAR15-26 (SEQ ID NO;
123); and
each said immunoglobulin single variable domain with binding specificity for EGFR competes for binding to EGFR with cetuximab. - View Dependent Claims (27, 29, 30, 31, 32, 33, 34, 41, 42, 43, 44)
- 117), TAR15-8 (SEQ ID NO;
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28. A ligand that has binding specificity for vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR), comprising a first immunoglobulin single variable domain with binding specificity for VEGF and a second immunoglobulin single variable domain with binding specificity for EGFR, wherein
said first immunoglobulin single variable domain competes for binding to VEGF with bevacizumab; - and
said second immunoglobulin single variable domain competes for binding to EGFR with cetuximab.
- and
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35-40. -40. (canceled)
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45. A ligand that has binding specificity for vascular endothelial growth factor (VEGF), comprising at least one immunoglobulin single variable domain with binding specificity for VEGF, wherein each said immunoglobulin single variable domain with binding specificity for VEGF competes for binding to VEGF with an anti-VEGF domain antibody (dAb) selected from the group consisting of TAR15-6 (SEQ ID NO:
- 117), TAR15-8 (SEQ ID NO;
119), and TAR15-26 (SEQ ID NO;
123). - View Dependent Claims (46, 49, 50, 51)
- 117), TAR15-8 (SEQ ID NO;
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47-48. -48. (canceled)
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64-68. -68. (canceled)
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71-74. -74. (canceled)
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77-78. -78. (canceled)
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81-86. -86. (canceled)
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91. (canceled)
- 92. A composition comprising a single domain antibody polypeptide construct that antagonizes human VEGF binding to a receptor, wherein said single domain antibody polypeptide construct comprises a CDR3 sequence that is the same that the sequence of CDR3 of a dAb selected from the group consisting of TAR15-1, TAR15-3, TAR15-4, TAR15-9, TAR15-10, TAR15-11, TAR15-12, TAR15-13, TAR15-14, TAR15-15, TAR15-16, TAR15-17, TAR15-18, TAR15-19, TAR15-20, TAR15-22, TAR15-5, TAR15-6, TAR15-7, TAR15-8, TAR15-23, TAR15-24, TAR15-25, TAR15-26, TAR15-27, TAR15-29, and TAR15-30.
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93. A composition comprising a single domain antibody polypeptide construct that antagonizes human VEGF binding to a receptor, wherein said single domain antibody polypeptide construct comprises an amino acid sequence selected from the group consisting of TAR15-1, TAR15-3, TAR15-4, TAR15-9, TAR15-10, TAR15-11, TAR15-12, TAR15-13, TAR15-14, TAR15-15, TAR15-16, TAR15-17, TAR15-18, TAR15-19, TAR15-20, TAR15-22, TAR15-5, TAR15-6, TAR15-7, TAR15-8, TAR15-23, TAR15-24, TAR15-25, TAR15-26, TAR15-27, TAR15-29, and TAR15-30 or a sequence at least 85% identical thereto.
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94-99. -99. (canceled)
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102. An immunoglobulin single variable domain polypeptide that binds VEGF, wherein the polypeptide has an amino acid sequence that is identical to the amino acid sequence of TAR15-6 (SEQ ID NO:
- 117), TAR15-8 (SEQ ID NO;
119), and TAR15-26 (SEQ ID NO;
123), or differs from the amino acid sequence of TAR15-6 (SEQ ID NO;
117), TAR15-8 (SEQ ID NO;
119), and TAR15-26 (SEQ ID NO;
123) at no more than 25 amino acid positions and has a CDR1 sequence that has at least 50% identity to the CDR1 sequence of TAR15-6 (SEQ ID NO;
117), TAR15-8 (SEQ ID NO;
119), and TAR15-26 (SEQ ID NO;
123).
- 117), TAR15-8 (SEQ ID NO;
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103. An immunoglobulin single variable domain polypeptide that binds to VEGF, wherein the polypeptide has an amino acid sequence that is identical to the amino acid sequence of TAR15-6 (SEQ ID NO:
- 117), TAR15-8 (SEQ ID NO;
119), and TAR15-26 (SEQ ID NO;
123), or differs from the amino acid sequence of TAR15-6 (SEQ ID NO;
117), TAR15-8 (SEQ ID NO;
119), and TAR15-26 (SEQ ID NO;
123) at no more than 25 amino acid positions and has a CDR2 sequence that has at least 50% identity to the CDR2 sequence of TAR15-6 (SEQ ID NO;
117), TAR15-8 (SEQ ID NO;
119), and TAR15-26 (SEQ ID NO;
123).
- 117), TAR15-8 (SEQ ID NO;
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104. An immunoglobulin single variable domain polypeptide that binds VEGF, wherein the polypeptide has an amino acid sequence that is identical to the amino acid sequence of TAR15-6 (SEQ ID NO:
- 117), TAR15-8 (SEQ ID NO;
119), and TAR15-26 (SEQ ID NO;
123), or differs from the amino acid sequence of TAR15-6 (SEQ ID NO;
117), TAR15-8 (SEQ ID NO;
119), and TAR15-26 (SEQ ID NO;
123) at no more than 25 amino acid positions and has a CDR3 sequence that has at least 50% identity to the CDR3 sequence of TAR15-6 (SEQ ID NO;
117), TAR15-8 (SEQ ID NO;
119), and TAR15-26 (SEQ ID NO;
123).
- 117), TAR15-8 (SEQ ID NO;
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105-107. -107. (canceled)
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108. An immunoglobulin single variable domain polypeptide that binds VEGF, wherein the dAb has an amino acid sequence that is identical to the amino acid sequence of TAR15-6 (SEQ ID NO:
- 117), TAR15-8 (SEQ ID NO;
119), and TAR15-26 (SEQ ID NO;
123), or differs from the amino acid sequence of TAR15-6 (SEQ ID NO;
117), TAR15-8 (SEQ ID NO;
119), and TAR15-26 (SEQ ID NO;
123) at no more than 25 amino acid positions and has a CDR1 sequence that has at least 50% identity to the CDR1 sequence of TAR15-6 (SEQ ID NO;
117), TAR15-8 (SEQ ID NO;
119), and TAR15-26 (SEQ ID NO;
123) and has a CDR2 sequence that has at least 50% identity to the CDR2 sequence of TAR15-6 (SEQ ID NO;
117), TAR15-8 (SEQ ID NO;
119), and TAR15-26 (SEQ ID NO;
123) and has a CDR3 sequence that has at least 50% identity to the CDR3 sequence of TAR15-6 (SEQ ID NO;
117), TAR15-8 (SEQ ID NO;
119), and TAR15-26 (SEQ ID NO;
123).
- 117), TAR15-8 (SEQ ID NO;
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109-114. -114. (canceled)
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115. A VEGF antagonist having a CDR1 sequence that has at least 50% identity to the CDR1 sequence of TAR15-6 (SEQ ID NO:
- 117), TAR15-8 (SEQ ID NO;
119), and TAR15-26 (SEQ ID NO;
123) and a CDR2 sequence that has at least 50% identity to the CDR2 sequence of TAR15-6 (SEQ ID NO;
117), TAR15-8 (SEQ ID NO;
119), and TAR15-26 (SEQ ID NO;
123) and a CDR3 sequence that has at least 50% identity to the CDR3 sequence of TAR15-6 (SEQ ID NO;
117), TAR15-8 (SEQ ID NO;
119), and TAR15-26 (SEQ ID NO;
123).
- 117), TAR15-8 (SEQ ID NO;
Specification