US2006233802A1PendingUtilityA1

Tumour necrosis factor binding ligands

66
Assignee: PEPTECH LTDPriority: Aug 7, 1989Filed: Jun 6, 2006Published: Oct 19, 2006
Est. expiryAug 7, 2009(expired)· nominal 20-yr term from priority
Inventors:Deborah RathjenRoger Aston
C07K 2317/21C07K 2317/55C07K 2317/76C07K 2317/73A61K 47/68C07K 2319/00A61P 35/00C07K 16/241C07K 2317/622A61K 47/6813C07K 2317/24C07K 2317/75A61K 38/00
66
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Claims

Abstract

The present invention relates to ligands which bind to human tumour necrosis factor alpha (TNF) in a manner such that upon binding of these ligands to TNF the biological activity of TNF is modified. In preferred forms the ligand binds to TNF in a manner such that the induction of endothelial procoagulant activity of the TNF is inhibited; the binding of TNF to receptors on endothelial cells is inhibited; the induction of fibrin deposition in the tumour and tumour regression activities of the TNF are enhanced; and the cytotoxicity and receptor binding activities of the TNF are unaffected or enhanced on tumour cells. The ligand is preferably an antibody, F(ab) fragment, single domain antibody (dABs), single chain antibody or a serum binding protein. It is preferred, however, that the ligand is a monoclonal antibody or F(ab) fragment thereof.

Claims

exact text as granted — not AI-modified
1 . An isolated antibody or fragment thereof that binds to mature human TNFα, 
 wherein the antibody is characterized in that when the antibody binds TNF-α the induction of endothelial procoagulant activity of TNF-α is inhibited,    wherein the antibody binds to TNF-α such that the epitope defined by the topographic regions of 1-18 (Val 1 -Arg 2 -Ser 3 -Ser 4 -Ser 5 -Arg 6 -Thr 7 -Pro 8 -Ser 9 -Asp 10 -Lys 11 -Pro 12 -Val 13 -Ala 14 -His 15 -Val 16 -Val 17 -Ala 18 ), 58-65 (Ile 58 -Tyr 59 -Ser 60 -Gln 61 -Val 62 -Leu 63 -Phe 64 -Lys 65 ), 115-125 (Tyr 115 -Glu 116 -Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 ) and 138-149 (Arg 138 -Pro 139 -Asp 140 -Tyr 141 -Leu 142 -Asp 143 -Phe 144 -Ala 145 -Glu 146 -Ser 147 -Gly 148 -Gln 149 ), or the topographic region of residues 1-18 (Val 1 -Arg 2 -Ser 3 -Ser 4 -Ser 5 -Arg 6 -Thr 7 -Pro 8 -Ser 9 -Asp 10 -Lys 11 -Pro 12 -Val 13 -Ala 14 -His 15 -Val 16 -Val 17 -Ala 18 ) and 108-128 (Gly 108 -Ala 109 -Glu 110 -Ala 111 -Lys 112 -Pro 113 -Trp 114 -Tyr 115 -Glu 116 -Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 -Leu 126 -Glu 127 -Lys 128 ), or the topographic region of residues 56-79 (Tyr 56 -Leu 57 -Ile 58 -Tyr 59 -Ser 60 -Gln 61 -Val 62 -Leu 63 -Phe 64 -Lys 65 -Gly 66 -Gln 67 -Gly 68 -Cys 69 -Pro 70 -Ser 71 -Thr 72 -His 73 -Val 74 -Leu 75 -Leu 76 -Thr 77 -His 78 -Thr 79 ), 110-127 (Glu 110 -Ala 111 -Lys 112 -Pro 113 -Trp 114 -Tyr 115 -Glu 116 -Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 -Leu 126 -Glu 127 ) and 135-155 (Glu 135 -Ile 136 -Asn 137 -Arg 138 -Pro 139 -Asp 140 -Tyr 141 -Leu 142 -Asp 143 -Phe 144 -Ala 145 -Glu 146 -Ser 147 -Gly 148 -Gln 149 -Val 150 -Tyr 151 -Phe 152 -Gly 153 -Ile 154 -Ile 155 ), or the topographic region of residues 1-30 (Val 1 -Arg 2 -Ser 3 -Ser 4 -Ser 5 -Arg 6 -Thr 7 -Pro 8 -Ser 9 -Asp 10 -Lys 11 -Pro 12 -Val 13 -Ala 14 -His 15 -Val 16 -Val 17 -Ala 18 -Asn 19 -Pro 20 Gln 21 Ala 22 -Glu 23 -Gly 24 -Gln 25 -Leu 26 -Gln 27 -Trp 28 -Leu 29 -Asn 30 ), 117-128 (Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 -Leu 126 -Glu 127 -Lys 128 ) and 141-153 (Tyr 141 -Leu 142 -Asp 143 -Phe 144 -Ala 145 -Glu 146 -Ser 147 -Gly 148 -Gln 149 -Val 150 -Tyr 151 -Phe 152 -Gly 153 ), or the topographic region of residues 22-40 (Ala 22 -Glu 23 -Gly 24 -Gln 25 -Leu 26 -Gln 27 -Trp 28 -Leu 29 -Asn 30 -Arg 31 -Arg 32 -Ala 33 -Asn 34 -Ala 35 -Leu 36 -Leu 37 -Ala 38 -Asn 39 -Gly 40 ), 49-97 (Val 49 -Val 50 -Pro 51 -Ser 52 -Glu 53 -Gly 54 -Leu 55 -Tyr 56 -Leu 57 -Ile 58 -Tyr 59 -Ser 60 -Gln 61 -Val 62 -Leu 63 -Phe 64 -Lys 65 -Gly 66 -Gln 67 -Gly 68 -Cys 69 -Pro 70 -Ser 71 -Thr 72 -His 73 -Val 74 -Leu 75 -Leu 76 -Thr 77 -His 78 -Thr 79 -Ile 80 -Ser 81 -Arg 82 -Ile 83 -Ala 84 -Val 85 -Ser 86 -Tyr 87 -Gln 88 -Thr 89 -Lys 90 -Val 91 -Asn 92 -Leu 93 -Leu 94 -Ser 95 -Ala 96 -Ile 97 ), 110-127 (Glu 110 -Ala 111 -Lys 112 -Pro 113 -Trp 114 -Tyr 115 -Glu 116 -Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 -Leu 126 -Glu 127 ) and 136-153 (Ile 136 -Asn 137 -Arg 138 -Pro 139 -Asp 140 -Tyr 141 -Leu 142 -Asp 143 -Phe 144 -Ala 145 -Glu 146 -Ser 147 -Gly 148 -Gln 149 -Val 150 -Tyr 151 -Phe 152 -Gly 153 ), or the topographic region of residues 1-20 (Val 1 -Arg 2 -Ser 3 -Ser 4 -Ser 5 -Arg 6 -Thr 7 -Pro 8 -Ser 9 -Asp 10 -Lys 11 -Pro 12 -Val 13 -Ala 14 -His 15 -Val 16 -Val 17 -Ala 18 -Asn 19 -Pro 20 ) and 76-90 (Leu 76 -Thr 77 -His 78 -Thr 79 -Ile 80 -Ser 81 -Arg 82 -Ile 83 -Ala 84 -Val 85 -Ser 86 -Tyr 87 -Gln 88 -Thr 89 -Lys 90 ), or the topographic region of residues 22-40 (Ala 22 -Glu 23 -Gly 24 -Gln 25 -Leu 26 -Gln 27 -Trp 28 -Leu 29 -Asn 30 -Arg 31 -Arg 32 -Ala 33 -Asn 34 -Ala 35 -Leu 36 -Leu 37 -Ala 38 -Asn 39 -Gly 40 ), 69-97 (Cys 69 -Pro 70 -Ser 71 -Thr 72 -His 73 -Val 74 -Leu 75 -Leu 76 -Thr 77 -His 78 -Thr 79 -Ile 80 -Ser 81 -Arg 82 -Ile 83 -Ala 84 -Val 85 -Ser 86 -Tyr 87 -Gln 88 -Thr 89 -Lys 90 -Val 91 -Asn 92 -Leu 93 -Leu 94 -Ser 95 -Ala 96 -Ile 97 ), 105-128 (Thr 105 -Pro 106 -Glu 107 -Gly 108 -Ala 109 -Glu 110 -Ala 111 -Lys 112 -Pro 113 -Trp 114 -Tyr 115 -Glu 116 -Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 120 -Gly 122 -Val 123 -Phe 124 -Gln 125 -Leu 126 -Glu 127 -Lys 128 ) and 135-155 (Glu 135 -Ile 136 -Asn 137 -Arg 138 -Pro 139 -Asp 140 -Tyr 141 -Leu 142 -Asp 143 -Phe 144 -Ala 145 -Glu 146 -Ser 147 -Gly 148 -Gln 149 -Val 150 -Tyr 151 -Phe 152 -Gly 153 -Ile 154 -Ile 155 ) is prevented from binding to mature human TNF-α receptor.    
     
     
         2 . An antibody or fragment thereof according to  claim 1 , 
 wherein the antibody binds to TNF-α such that the epitope defined by the topographic regions of 1-18 (Val 1 -Arg 2 -Ser 3 -Ser 4 -Ser 5 -Arg 6 -Thr 7 -Pro 8 -Ser 9 -Asp 10 -Lys 11 -Pro 12 -Val 13 -Ala 14 -His 15 -Val 16 -Val 17 -Ala 18 ), 58-65 (Ile 58 -Tyr 59 -Ser 60 -Gln 61 -Val 62 -Leu 63 -Phe 64 -Lys 65 ), 115-125 (Tyr 115 -Glu 116 -Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 ) and 138-149 (Arg 138 -Pro 139 -Asp 140 -Tyr 141 -Leu 142 -Asp 143 -Phe 144 -Ala 145 -Glu 146 -Ser 147 -Gly 148 -Gln 149 ), or the topographic region of residues 1-18 (Val 1 -Arg 2 -Ser 3 -Ser 4 -Ser 5 -Arg 6 -Thr 7 -Pro 8 -Ser 9 -Asp 10 -Lys 11 -Pro 12 -Val 13 -Ala 14 -His 15 -Val 16 -Val 17 -Ala 18 ) and 108-128 (Gly 108 -Ala 109 -Glu 110 -Ala 111 -Lys 112 -Pro 113 -Trp 114 -Tyr 115 -Glu 116 -Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 -Leu 126 -Glu 127 -Lys 128 ), or the topographic region of residues 56-79 (Tyr 56 -Leu 57 -Ile 58 -Tyr 59 -Ser 60 -Gln 61 -Val 62 -Leu 63 -Phe 64 -Lys 65 -Gly 66 -Gln 67 -Gly 68 -Cys 69 -Pro 70 -Ser 71 -Thr 72 -His 73 -Val 74 -Leu 75 -Leu 76 -Thr 77 -His 78 -Thr 79 ), 110-127 (Glu 110 -Ala 111 -Lys 112 -Pro 113 -Trp 114 -Tyr 115 -Glu 116 -Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 -Leu 126 -Glu 127 ) and 135-155 (Glu 135 -Ile 136 -Asn 137 -Arg 138 -Pro 139 -Asp 140 -Tyr 141 -Leu 142 -Asp 143 -Phe 144 -Ala 145 -Glu 146 -Ser 147 -Gly 148 -Gln 149 -Val 150 -Tyr 151 -Phe 152 -Gly 153 -Ile 154 -Ile 155 ), or the topographic region of residues 1-20 (Val 1 -Arg 2 -Ser 3 -Ser 4 -Ser 5 -Arg 6 -Thr 7 -Pro 8 -Ser 9 -Asp 10 -Lys 11 -Pro 12 -Val 13 -Ala 14 -His 15 -Val 16 -Val 17 -Ala 18 -Asn 19 -Pro 20 ) and 76-90 (Leu 76 -Thr 77 -His 78 -Thr 79 -Ile 80 -Ser 81 -Arg 82 -Ile 83 -Ala 84 -Val 85 -Ser 86 -Tyr 87 -Gln 88 -Thr 89 -Lys 90 ), or the topographic region of residues 22-40 (Ala 22 -Glu 23 -Gly 24 -Gln 25 -Leu 26 -Gln 27 -Trp 28 -Leu 29 -Asn 30 -Arg 31 -Arg 32 -Ala 33 -Asn 34 -Ala 35 -Leu 36 -Leu 37 -Ala 38 -Asn 39 -Gly 40 ), 69-97 (Cys 69 -Pro 70 -Ser 71 -Thr 72 -His 73 -Val 74 -Leu 75 -Leu 76 -Thr 77 -His 78 -Thr 79 -Ile 80 -Ser 81 -Arg 82 -Ile 83 -Ala 84 -Val 85 -Ser 86 -Tyr 87 -Gln 88 -Thr 89 -Lys 90 -Val 91 -Asn 92 -Leu 93 -Leu 94 -Ser 95 -Ala 96 -Ile 97 ), 105-128 (Thr 105 -Pro 106 -Glu 107 -Gly 108 -Ala 109 -Glu 110 -Ala 111 -Lys 112 -Pro 113 -Trp 114 -Tyr 115 -Glu 116 -Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 -Leu 126 -Glu 127 -Lys 128 ) and 135-155 (Glu 135 -Ile 136 -Asn 137 -Arg 138 -Pro 139 -Asp 140 -Tyr 141 -Leu 142 -Asp 143 -Phe 144 -Ala 145 -Glu 146 -Ser 147 -Gly 148 -Gln 149 -Val 150 -Tyr 151 -Phe 152 -Gly 153 -Ile 154 -Ile 155 ) is prevented from binding to mature human TNF-α receptor and    wherein the antibody inhibits cytotoxicity.    
     
     
         3 . An antibody or fragment thereof according to  claim 1 , 
 wherein the antibody binds to TNF-α such that the epitope defined by the topographic regions of 1-18 (Val 1 -Arg 2 -Ser 3 -Ser 4 -Ser 5 -Arg 6 -Thr 7 -Pro 8 -Ser 9 -Asp 10 -Lys 11 -Pro 12 -Val 13 -Ala 14 -His 15 -Val 16 -Val 17 -Ala 18 ), 58-65 (Ile 58 -Tyr 59 -Ser 60 -Gln 61 -Val 62 -Leu 63 -Phe 64 -Lys 65 ), 115-125 (Tyr 115 -Glu 116 -Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 ) and 138-149 (Arg 138 -Pro 139 -Asp 140 -Tyr 141 -Leu 142 -Asp 143 -Phe 144 -Ala 145 -Glu 146 -Ser 147 -Gly 148 -Gln 149 ), or the topographic region of residues 1-18 (Val 1 -Arg 2 -Ser 3 -Ser 4 -Ser 5 -Arg 6 -Thr 7 -Pro 8 -Ser 9 -Asp 10 -Lys 11 -Pro 12 -Val 13 -Ala 14 -His 15 -Val 16 -Val 17 -Ala 18 ) and 108-128 (Gly 108 -Ala 109 -Glu 110 -Ala 111 -Lys 112 -Pro 113 -Trp 114 -Tyr 115 -Glu 116 -Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 -Leu 126 -Glu 127 -Lys 128 ), or the topographic region of residues 56-79 (Tyr 56 -Leu 57 -Ile 58 -Tyr 59 -Ser 60 -Gln 61 -Val 62 -Leu 63 -Phe 64 -Lys 65 -Gly 66 -Gln 67 -Gly 68 -Cys 69 -Pro 70 -Ser 71 -Thr 72 -His 73 -Val 74 -Leu 75 -Leu 76 -Thr 77 -His 78 -Thr 79 ), 110-127 (Glu 110 -Ala 111 -Lys 112 -Pro 113 -Trp 114 -Tyr 115 -Glu 116 -Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 -Leu 126 -Glu 127 ) and 135-155 (Glu 135 -Ile 136 -Asn 137 -Arg 138 -Pro 139 -Asp 140 -Tyr 141 -Leu 142 -Asp 143 -Phe 144 -Ala 145 -Glu 146 -Ser 147 -Gly 148 -Gln 149 -Val 150 -Tyr 151 -Phe 152 -Gly 153 -Ile 154 -Ile 155 ), or the topographic region of residues 1-20 (Val 1 -Arg 2 -Ser 3 -Ser 4 -Ser 5 -Arg 6 -Thr 7 -Pro 8 -Ser 9 -Asp 10 -Lys 11 -Pro 12 -Val 13 -Ala 14 -His 15 -Val 16 -Val 17 -Ala 18 -Asn 19 -Pro 20 ) and 76-90 (Leu 76 -Thr 77 -His 78 -Thr 79 -Ile 80 -Ser 81 -Arg 82 -Ile 83 -Ala 84 -Val 85 -Ser 86 -Tyr 87 -Gln 88 -Thr 89 -Lys 90 ), or the topographic region of residues 22-40 (Ala 22 -Glu 23 -Gly 24 -Gln 25 -Leu 26 -Gln 27 -Trp 28 -Leu 29 -Asn 30 -Arg 31 -Arg 32 -Ala 33 -Asn 34 -Ala 35 -Leu 36 -Leu 37 -Ala 38 -Asn 39 -Gly 40 ), 69-97 (Cys 69 -Pro 70 -Ser 71 -Thr 72 -His 73 -Val 74 -Leu 75 -Leu 76 -Thr 77 -His 78 -Thr 79 -Ile 80 -Ser 81 -Arg 82 -Ile 83 -Ala 84 -Val 85 -Ser 86 -Tyr 87 -Gln 88 -Thr 89 -Lys 90 -Val 91 -Asn 92 -Leu 93 -Leu 94 -Ser 95 -Ala 96 -Ile 97 ), 105-128 (Thr 105 -Pro 106 -Glu 107 -Gly 108 -Ala 109 -Glu 110 -Ala 111 -Lys 112 -Pro 113 -Trp 114 -Tyr 115 -Glu 116 -Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 -Leu 126 -Glu 127 -Lys 128 ) and 135-155 (Glu 135 -Ile 136 -Asn 137 -Arg 138 -Pro 139 -Asp 140 -Tyr 141 -Leu 142 -Asp 143 -Phe 144 -Ala 145 -Glu 146 -Ser 147 -Gly 148 -Gln 149 -Val 150 -Tyr 151 -Phe 152 -Gly 153 -Ile 154 -Ile 155 ) is prevented from binding to mature human TNF-α receptor, and    wherein the antibody inhibits tumor regression.    
     
     
         4 . An antibody or fragment thereof according to  claim 1 , 
 wherein the antibody binds to TNF-α such that the epitope defined by the topographic regions of wherein the antibody binds to TNF-α such that the epitope defined by the topographic region of residues 1-30 (Val 1 -Arg 2 -Ser 3 -Ser 4 -Ser 5 -Arg 6 -Thr 7 -Pro 8 -Ser 9 -Asp 10 -Lys 11 -Pro 12 -Val 13 -Ala 14 -His 15 -Val 16 -Val 17 -Ala 18 -Asn 19 -Pro 20 Gln 21 Ala 22 -Glu 23 -Gly 24 -Gln 25 -Leu 26 -Gln 27 -Trp 28 -Leu 29 -Asn 30 ), 117-128 (Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 -Leu 126 -Glu 127 -Lys 128 ) and 141-153 (Tyr 141 -Leu 142 -Asp 143 -Phe 144 -Ala 145 -Glu 146 -Ser 147 -Gly 148 -Gln 149 -Val 150 -Tyr 151 -Phe 152 -Gly 153 ), or the topographic region of residues 22-40 (Ala 22 -Glu 23 -Gly 24 -Gln 25 -Leu 26 -Gln 27 -Trp 28 -Leu 29 -Asn 30 -Arg 31 -Arg 32 -Ala 33 -Asn 34 -Ala 35 -Leu 36 -Leu 37 -Ala 38 -Asn 39 -Gly 40 ), 49-97 (Val 49 -Val 50 -Pro 51 -Ser 52 -Glu 53 -Gly 54 -Leu 55 -Tyr 56 -Leu 57 -Ile 58 -Tyr 59 -Ser 60 -Gln 61 -Val 62 -Leu 63 -Phe 64 -Lys 65 -Gly 66 -Gln 67 -Gly 68 -Cys 69 -Pro 70 -Ser 71 -Thr 72 -His 73 -Val 74 -Leu 75 -Leu 76 -Thr 77 -His 78 -Thr 79 -Ile 80 -Ser 81 -Arg 82 -Ile 83 -Ala 84 -Val 85 -Ser 86 -Tyr 87 -Gln 88 -Thr 89 -Lys 90 -Val 91 -Asn 92 -Leu 93 -Leu 94 -Ser 95 -Ala 96 -Ile 97 ), 110-127 (Glu 110 -Ala 111 -Lys 112 -Pro 113 -Trp 114 -Tyr 115 -Glu 116 -Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 -Leu 126 -Glu 127 ) and 136-153 (Ile 136 -Asn 137 -Arg 138 -Pro 139 -Asp 140 -Tyr 141 -Leu 142 -Asp 143 -Phe 144 -Ala 145 -Glu 146 -Ser 147 -Gly 148 -Gln 149 -Val 150 -Tyr 151 -Phe 152 -Gly 153 ) is prevented from binding to mature human TNF-α receptor and    wherein the antibody has no effect on cytotoxicity.    
     
     
         5 . An antibody or fragment thereof according to any one of claims  1 - 4 , wherein the antibody is a monoclonal antibody.  
     
     
         6 . An antibody or fragment thereof according to  claim 1 , wherein the antibody is selected from the group consisting of MAb 1, as produced by hybridoma cell line ECACC Accession No. 89080301, MAb 21, as produced by hybridoma cell line ECACC Accession No. 90012432, MAb 32, as produced by hybridoma cell line ECACC Accession No. 89080302, MAb 42, as produced by hybridoma cell line ECACC Accession No. 89080304, MAb 47, as produced by hybridoma cell line ECACC Accession No. 89121402, MAb 53, as produced by hybridoma cell line ECACC Accession No. 90012433, and MAb 54, as produced by hybridoma cell line ECACC Accession No. 89083103.  
     
     
         7 . An antibody or fragment thereof according to any one of claims  1 - 4 , wherein the antibody is a humanized antibody.  
     
     
         8 . An antibody or fragment thereof according to any one of claims  1 - 4 , wherein the antibody is a chimeric antibody.  
     
     
         9 . An antibody or fragment thereof according to any one of claims  1 - 4 , wherein the antibody is a human antibody.  
     
     
         10 . A composition comprising an isolated antibody or fragment thereof that binds to mature human TNF-α, 
 wherein the antibody is characterized in that when the antibody binds to TNF-α the induction of endothelial procoagulant activity is inhibited,    wherein the antibody binds to TNF-α such that the epitope defined by the topographic regions of 1-18 (Val 1 -Arg 2 -Ser 3 -Ser 4 -Ser 5 -Arg 6 -Thr 7 -Pro 8 -Ser 9 -Asp 10 -Lys 11 -Pro 12 -Val 13 -Ala 14 -His 15 -Val 16 -Val 17 -Ala 18 ), 58-65 (Ile 58 -Tyr 59 -Ser 60 -Gln 61 -Val 62 -Leu 63 -Phe 64 -Lys 65 ), 115-125 (Tyr 115 -Glu 116 -Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 ) and 138-149 (Arg 138 -Pro 139 -Asp 140 -Tyr 141 -Leu 142 -Asp 143 -Phe 144 -Ala 145 -Glu 146 -Ser 147 -Gly 148 -Gln 149 ), or the topographic region of residues 1-18 (Val 1 -Arg 2 -Ser 3 -Ser 4 -Ser 5 -Arg 6 -Thr 7 -Pro 8 -Ser 9 -Asp 10 -Lys 11 -Pro 12 -Val 13 -Ala 14 -His 15 -Val 16 -Val 17 -Ala 18 ) and 108-128 (Gly 108 -Ala 109 -Glu 110 -Ala 111 -Lys 112 -Pro 113 -Trp 114 -Tyr 115 -Glu 116 -Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 -Leu 126 -Glu 127 -Lys 128 ), or the topographic region of residues 56-79 (Tyr 56 -Leu 57 -Ile 58 -Tyr 59 -Ser 60 -Gln 61 -Val 62 -Leu 63 -Phe 64 -Lys 65 -Gly 66 -Gln 67 -Gly 68 -Cys 69 -Pro 70 -Ser 71 -Thr 72 -His 73 -Val 74 -Leu 75 -Leu 76 -Thr 77 -His 78 -Thr 79 ), 110-127 (Glu 110 -Ala 111 -Lys 112 -Pro 113 -Trp 114 -Tyr 115 -Glu 116 -Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 -Leu 126 -Glu 127 ) and 135-155 (Glu 135 -Ile 136 -Asn 137 -Arg 138 -Pro 139 -Asp 140 -Tyr 141 -Leu 142 -Asp 143 -Phe 144 -Ala 145 -Glu 146 -Ser 147 -Gly 148 -Gln 149 -Val 150 -Tyr 151 -Phe 152 -Gly 153 -Ile 154 -Ile 155 ), or the topographic region of residues 1-30 (Val 1 -Arg 2 -Ser 3 -Ser 4 -Ser 5 -Arg 6 -Thr 7 -Pro 8 -Ser 9 -Asp 10 -Lys 11 -Pro 12 -Val 13 -Ala 14 -His 15 -Val 16 -Val 17 -Ala 18 -Asn 19 -Pro 20 Gln 21 Ala 22 -Glu 23 -Gly 24 -Gln 25 -Leu 26 -Gln 27 -Trp 28 -Leu 29 -Asn 30 ), 117-128 (Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 -Leu 126 -Glu 127 -Lys 128 ) and 141-153 (Tyr 141 -Leu 142 -Asp 143 -Phe 144 -Ala 145 -Glu 146 -Ser 147 -Gly 148 -Gln 149 -Val 150 -Tyr 151 -Phe 152 -Gly 153 ), or the topographic region of residues 22-40 (Ala 22 -Glu 23 -Gly 24 -Gln 25 -Leu 26 -Gln 27 -Trp 28 -Leu 29 -Asn 30 -Arg 31 -Arg 32 -Ala 33 -Asn 34 -Ala 35 -Leu 36 -Leu 37 -Ala 38 -Asn 39 -Gly 40 ), 49-97 (Val 49 -Val 50 -Pro 51 -Ser 52 -Glu 53 -Gly 54 -Leu 55 -Tyr 56 -Leu 57 -Ile 58 -Tyr 59 -Ser 60 -Gln 61 -Val 62 -Leu 63 -Phe 64 -Lys 65 -Gly 66 -Gln 67 -Gly 68 -Cys 69 -Pro 70 -Ser 71 -Thr 72 -His 73 -Val 74 -Leu 75 -Leu 76 -Thr 77 -His 78 -Thr 79 -Ile 80 -Ser 81 -Arg 82 -Ile 83 -Ala 84 -Val 85 -Ser 86 -Tyr 87 -Gln 88 -Thr 89 -Lys 90 -Val 91 -Asn 92 -Leu 93 -Leu 94 -Ser 95 -Ala 96 -Ile 97 ), 110-127 (Glu 110 -Ala 111 -Lys 112 -Pro 113 -Trp 114 -Tyr 115 -Glu 116 -Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 -Leu 126 -Glu 127 ) and 136-153 (Ile 136 -Asn 137 -Arg 138 -Pro 139 -Asp 140 -Tyr 141 -Leu 142 -Asp 143 -Phe 144 -Ala 145 -Glu 146 -Ser 147 -Gly 148 -Gln 149 -Val 150 -Tyr 151 -Phe 152 -Gly 153 ), or the topographic region of residues 1-20 (Val 1 -Arg 2 -Ser 3 -Ser 4 -Ser 5 -Arg 6 -Thr 7 -Pro 8 -Ser 9 -Asp 10 -Lys 11 -Pro 12 -Val 13 -Ala 14 -His 15 -Val 16 -Val 17 -Ala 18 -Asn 19 -Pro 20 ) and 76-90 (Leu 76 -Thr 77 -His 78 -Thr 79 -Ile 80 -Ser 81 -Arg 82 -Ile 83 -Ala 84 -Val 85 -Ser 86 -Tyr 87 -Gln 88 -Thr 89 -Lys 90 ), or the topographic region of residues 22-40 (Ala 22 -Glu 23 -Gly 24 -Gln 25 -Leu 26 -Gln 27 -Trp 28 -Leu 29 -Asn 30 -Arg 31 -Arg 32 -Ala 33 -Asn 34 -Ala 35 -Leu 36 -Leu 37 -Ala 38 -Asn 39 -Gly 40 ), 69-97 (Cys 69 -Pro 70 -Ser 71 -Thr 72 -His 73 -Val 74 -Leu 75 -Leu 76 -Thr 77 -His 78 -Thr 79 -Ile 80 -Ser 81 -Arg 82 -Ile 83 -Ala 84 -Val 85 -Ser 86 -Tyr 87 -Gln 88 -Thr 89 -Lys 90 -Val 91 -Asn 92 -Leu 93 -Leu 94 -Ser 95 -Ala 96 -Ile 97 ), 105-128 (Thr 105 -Pro 106 -Glu 107 -Gly 108 -Ala 109 -Glu 110 -Ala 111 -Lys 112 -Pro 113 -Trp 114 -Tyr 115 -Glu 116 -Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 -Leu 126 -Glu 127 -Lys 128 ) and 135-155 (Glu 135 -Ile 136 -Asn 137 -Arg 138 -Pro 139 -Asp 140 -Tyr 141 -Leu 142 -Asp 143 -Phe 144 -Ala 145 -Glu 146 -Ser 147 -Gly 148 -Gln 149 -Val 150 -Tyr 151 -Phe 152 -Gly 153 -Ile 154 -Ile 155 ) is prevented from binding to mature human TNF-α receptor.    
     
     
         11 . A composition according to  claim 10 , 
 wherein the antibody binds to TNF-α such that the epitope defined by the topographic regions of 1-18 (Val 1 -Arg 2 -Ser 3 -Ser 4 -Ser 5 -Arg 6 -Thr 7 -Pro 8 -Ser 9 -Asp 10 -Lys 11 -Pro 12 -Val 13 -Ala 14 -His 15 -Val 16 -Val 17 -Ala 18 ), 58-65 (Ile 58 -Tyr 59 -Ser 60 -Gln 61 -Val 62 -Leu 63 -Phe 64 -Lys 65 ), 115-125 (Tyr 115 -Glu 116 -Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 ) and 138-149 (Arg 138 -Pro 139 -Asp 140 -Tyr 141 -Leu 142 -Asp 143 -Phe 144 -Ala 145 -Glu 146 -Ser 147 -Gly 148 -Gln 149 ), or the topographic region of residues 1-18 (Val 1 -Arg 2 -Ser 3 -Ser 4 -Ser 5 -Arg 6 -Thr 7 -Pro 8 -Ser 9 -Asp 10 -Lys 11 -Pro 12 -Val 13 -Ala 14 -His 15 -Val 16 -Val 17 -Ala 18 ) and 108-128 (Gly 108 -Ala 109 -Glu 110 -Ala 111 -Lys 112 -Pro 113 -Trp 114 -Tyr 115 -Glu 116 -Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 -Leu 126 -Glu 127 -Lys 128 ), or the topographic region of residues 56-79 (Tyr 56 -Leu 57 -Ile 58 -Tyr 59 -Ser 60 -Gln 61 -Val 62 -Leu 63 -Phe 64 -Lys 65 -Gly 66 -Gln 67 -Gly 68 -Cys 69 -Pro 70 -Ser 71 -Thr 72 -His 73 -Val 74 -Leu 75 -Leu 76 -Thr 77 -His 78 -Thr 79 ), 110-127 (Glu 110 -Ala 111 -Lys 112 -Pro 113 -Trp 114 -Tyr 115 -Glu 116 -Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 -Leu 126 -Glu 127 ) and 135-155 (Glu 135 -Ile 136 -Asn 137 -Arg 138 -Pro 139 -Asp 140 -Tyr 141 -Leu 142 -Asp 143 -Phe 144 -Ala 145 -Glu 146 -Ser 147 -Gly 148 -Gln 149 -Val 150 -Tyr 151 -Phe 152 -Gly 153 -Ile 154 -Ile 155 ), or the topographic region of residues 1-20 (Val 1 -Arg 2 -Ser 3 -Ser 4 -Ser 5 -Arg 6 -Thr 7 -Pro 8 -Ser 9 -Asp 10 -Lys 11 -Pro 12 -Val 13 -Ala 14 -His 15 -Val 16 -Val 17 -Ala 18 -Asn 19 -Pro 20 ) and 76-90 (Leu 76 -Thr 77 -His 78 -Thr 79 -Ile 80 -Ser 81 -Arg 82 -Ile 83 -Ala 84 -Val 85 -Ser 86 -Tyr 87 -Gln 88 -Thr 89 -Lys 90 ), or the topographic region of residues 22-40 (Ala 22 -Glu 23 -Gly 24 -Gln 25 -Leu 26 -Gln 27 -Trp 28 -Leu 29 -Asn 30 -Arg 31 -Arg 32 -Ala 33 -Asn 34 -Ala 35 -Leu 36 -Leu 37 -Ala 38 -Asn 39 -Gly 40 ), 69-97 (Cys 69 -Pro 70 -Ser 71 -Thr 72 -His 73 -Val 74 -Leu 75 -Leu 76 -Thr 77 -His 78 -Thr 79 -Ile 80 -Ser 81 -Arg 82 -Ile 83 -Ala 84 -Val 85 -Ser 86 -Tyr 87 -Gln 88 -Thr 89 -Lys 90 -Val 91 -Asn 92 -Leu 93 -Leu 94 -Ser 95 -Ala 96 -Ile 97 ), 105-128 (Thr 105 -Pro 106 -Glu 107 -Gly 108 -Ala 109 -Glu 110 -Ala 111 -Lys 112 -Pro 113 -Trp 114 -Tyr 115 -Glu 116 -Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 -Leu 126 -Glu 127 -Lys 128 ) and 135-155 (Glu 135 -Ile 136 -Asn 137 -Arg 138 -Pro 139 -Asp 140 -Tyr 141 -Leu 142 -Asp 143 -Phe 144 -Ala 145 -Glu 146 -Ser 147 -Gly 148 -Gln 149 -Val 150 -Tyr 151 -Phe 152 -Gly 153 -Ile 154 -Ile 155 ), is prevented from binding to mature human TNF-α receptor, and    wherein the antibody inhibits cytotoxicity.    
     
     
         12 . A composition according to  claim 10 , 
 wherein the antibody binds to TNF-α such that the epitope defined by the topographic regions of 1-18 (Val 1 -Arg 2 -Ser 3 -Ser 4 -Ser 5 -Arg 6 -Thr 7 -Pro 8 -Ser 9 -Asp 10 -Lys 11 -Pro 12 -Val 13 -Ala 14 -His 15 -Val 16 -Val 17 -Ala 18 ), 58-65 (Ile 58 -Tyr 59 -Ser 60 -Gln 61 -Val 62 -Leu 63 -Phe 64 -Lys 65 ), 115-125 (Tyr 115 -Glu 116 -Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 ) and 138-149 (Arg 138 -Pro 139 -Asp 140 -Tyr 141 -Leu 142 -Asp 143 -Phe 144 -Ala 145 -Glu 146 -Ser 147 -Gly 148 -Gln 149 ), or the topographic region of residues 1-18 (Val 1 -Arg 2 -Ser 3 -Ser 4 -Ser 5 -Arg 6 -Thr 7 -Pro 8 -Ser 9 -Asp 10 -Lys 11 -Pro 12 -Val 13 -Ala 14 -His 15 -Val 16 -Val 17 -Ala 18 ) and 108-128 (Gly 108 -Ala 109 -Glu 110 -Ala 111 -Lys 112 -Pro 113 -Trp 114 -Tyr 115 -Glu 116 -Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 Leu 126 -Glu 127 -Lys 128 ), or the topographic region of residues 56-79 (Tyr 56 -Leu 57 -Ile 58 -Tyr 59 -Ser 60 -Gln 61 -Val 62 -Leu 63 -Phe 64 -Lys 65 -Gly 66 -Gln 67 -Gly 68 -Cys 69 -Pro 70 -Ser 71 -Thr 72 -His 73 -Val 74 -Leu 75 -Leu 76 -Thr 77 -His 78 -Thr 79 ), 110-127 (Glu 110 -Ala 111 -Lys 112 -Pro 113 -Trp 114 -Tyr 115 -Glu 116 -Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 -Leu 126 -Glu 127 ) and 135-155 (Glu 135 -Ile 136 -Asn 137 -Arg 138 -Pro 139 -Asp 140 -Tyr 141 -Leu 142 -Asp 143 -Phe 144 -Ala 145 -Glu 146 -Ser 147 -Gly 148 -Gln 149 -Val 150 -Tyr 151 -Phe 152 -Gly 153 -Ile 154 -Ile 155 ) or the topographic region of residues 1-20 (Val 1 -Arg 2 -Ser 3 -Ser 4 -Ser 5 -Arg 6 -Thr 7 -Pro 8 -Ser 9 -Asp 10 -Lys 11 -Pro 12 -Val 13 -Ala 14 -His 15 -Val 16 -Val 17 -Ala 18 -Asn 19 -Pro 20 ) and 76-90 (Leu 76 -Thr 77 -His 78 -Thr 79 -Ile 80 -Ser 81 -Arg 82 -Ile 83 -Ala 84 -Val 85 -Ser 86 -Tyr 87 -Gln 88 -Thr 89 -Lys 90 ), or the topographic region of residues 22-40 (Ala 22 -Glu 23 -Gly 24 -Gln 25 -Leu 26 -Gln 27 -Trp 28 -Leu 29 -Asn 30 -Arg 31 -Arg 32 -Ala 33 -Asn 34 -Ala 35 -Leu 36 -Leu 37 -Ala 38 -Asn 39 -Gly 40 ), 69-97 (Cys 69 -Pro 70 -Ser 71 -Thr 72 -His 73 -Val 74 -Leu 75 -Leu 76 -Thr 77 -His 78 -Thr 79 -Ile 80 -Ser 81 -Arg 82 -Ile 83 -Ala 84 -Val 85 -Ser 86 -Tyr 87 -Gln 88 -Thr 89 -Lys 90 -Val 91 -Asn 92 -Leu 93 -Leu 94 -Ser 95 -Ala 96 -Ile 97 ), 105-128 (Thr 105 -Pro 106 -Glu 107 -Gly 108 -Ala 109 -Glu 110 -Ala 111 -Lys 112 -Pro 113 -Trp 114 -Tyr 115 -Glu 116 -Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 -Leu 126 -Glu 127 -Lys 128 ) and 135-155 (Glu 135 -Ile 136 -Asn 137 -Arg 138 -Pro 139 -Asp 140 -Tyr 141 -Leu 142 -Asp 143 -Phe 144 -Ala 145 -Glu 146 -Ser 147 -Gly 148 -Gln 149 -Val 150 -Tyr 151 -Phe 152 -Gly 153 -Ile 154 -Ile 155 ) is prevented from binding to mature human TNF-α receptor, and    wherein the antibody inhibits tumor regression.    
     
     
         13 . A composition according to  claim 10 , 
 wherein the antibody binds to TNF-α such that the epitope defined by the topographic regions of wherein the antibody binds to TNF-α such that the epitope defined by the topographic region of residues 1-30 (Val 1 -Arg 2 -Ser 3 -Ser 4 -Ser 5 -Arg 6 -Thr 7 -Pro 8 -Ser 9 -Asp 10 -Lys 11 -Pro 12 -Val 13 -Ala 14 -His 15 -Val 16 -Val 17 -Ala 18 -Asn 19 -Pro 20 Gln 21 Ala 22 -Glu 23 -Gly 24 -Gln 25 -Leu 26 -Gln 27 -Trp 28 -Leu 29 -Asn 30 ), 117-128 (Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 -Leu 126 -Glu 127 -Lys 128 ) and 141-153 (Tyr 141 -Leu 142 -Asp 143 -Phe 144 -Ala 145 -Glu 146 -Ser 147 -Gly 148 -Gln 149 -Val 150 -Tyr 151 -Phe 152 -Gly 153 ) or the topographic region of residues 22-40 (Ala 22 -Glu 23 -Gly 24 -Gln 25 -Leu 26 -Gln 27 -Trp 28 -Leu 29 -Asn 30 -Arg 31 -Arg 32 -Ala 33 -Asn 34 -Ala 35 -Leu 36 -Leu 37 -Ala 38 -Asn 39 -Gly 40 ), 49-97 (Val 49 -Val 50 -Pro 51 -Ser 52 -Glu 53 -Gly 54 -Leu 55 -Tyr 56 -Leu 57 -Ile 58 -Tyr 59 -Ser 60 -Gln 61 -Val 62 -Leu 63 -Phe 64 -Lys 65 -Gly 66 -Gln 67 -Gly 68 -Cys 69 -Pro 70 -Ser 71 -Thr 72 -His 73 -Val 74 -Leu 75 -Leu 76 -Thr 77 -His 78 -Thr 79 -Ile 80 -Ser 81 -Arg 82 -Ile 83 -Ala 84 -Val 85 -Ser 86 -Tyr 87 -Gln 88 -Thr 89 -Lys 90 -Val 91 -Asn 92 -Leu 93 -Leu 94 -Ser 95 -Ala 96 -Ile 97 ), 110-127 (Glu 110 -Ala 111 -Lys 112 -Pro 113 -Trp 114 -Tyr 115 -Glu 116 -Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 -Leu 126 -Glu 127 ) and 136-153 (Ile 136 -Asn 137 -Arg 138 -Pro 139 -Asp 140 -Tyr 141 -Leu 142 -Asp 143 -Phe 144 -Ala 145 -Glu 146 -Ser 147 -Gly 148 -Gln 149 -Val 150 -Tyr 151 -Phe 152 -Gly 153 ) is prevented from binding to mature human TNF-α receptor and    wherein the antibody has no effect on cytotoxicity.    
     
     
         14 . A composition according to any one of claims  10 - 13 , wherein the antibody is a monoclonal antibody.  
     
     
         15 . A composition according to  claim 10 , wherein the antibody is selected from the group consisting of MAb 1, as produced by hybridoma cell line ECACC Accession No. 89080301, MAb 21, as produced by hybridoma cell line ECACC Accession No. 90012432, MAb 32, as produced by hybridoma cell line ECACC Accession No. 89080302, MAb 42, as produced by hybridoma cell line ECACC Accession No. 89080304, MAb 47, as produced by hybridoma cell line ECACC Accession No. 89121402, MAb 53, as produced by hybridoma cell line ECACC Accession No. 90012433, and MAb 54, as produced by hybridoma cell line ECACC Accession No. 89083103.  
     
     
         16 . A composition according to any one of claims  10 - 13 , wherein the antibody is a humanized antibody.  
     
     
         17 . A composition according to any one of claims  10 - 13 , wherein the antibody is a chimeric antibody.  
     
     
         18 . A composition according to any one of claims  10 - 13 , wherein the antibody is a human antibody.  
     
     
         19 . An isolated single chain antibody that binds to mature human TNF-α, 
 wherein the antibody is characterized in that when the antibody binds to TNF-α the induction of endothelial procoagulant activity is inhibited,    wherein the antibody binds to TNF-α such that the epitope defined by the topographic regions of 1-18 (Val 1 -Arg 2 -Ser 3 -Ser 4 -Ser 5 -Arg 6 -Thr 7 -Pro 8 -Ser 9 -Asp 10 -Lys 11 -Pro 12 -Val 13 -Ala 14 -His 15 -Val 16 -Val 17 -Ala 18 ), 58-65 (Ile 58 -Tyr 59 -Ser 60 -Gln 61 -Val 62 -Leu 63 -Phe 64 -Lys 65 ), 115-125 (Tyr 115 -Glu 116 -Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 ) and 138-149 (Arg 138 -Pro 139 -Asp 140 -Tyr 141 -Leu 142 -Asp 143 -Phe 144 -Ala 145 -Glu 146 -Ser 147 -Gly 148 -Gln 149 ), or the topographic region of residues 1-18 (Val 1 -Arg 2 -Ser 3 -Ser 4 -Ser 5 -Arg 6 -Thr 7 -Pro 8 -Ser 9 -Asp 10 -Lys 11 -Pro 12 -Val 13 -Ala 14 -His 15 -Val 16 -Val 17 -Ala 18 ) and 108-128 (Gly 108 -Ala 109 -Glu 110 -Ala 111 -Lys 112 -Pro 113 -Trp 114 -Tyr 115 -Glu 116 -Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 Leu 126 -Glu 127 -Lys 128 ), or the topographic region of residues 56-79 (Tyr 56 -Leu 57 -Ile 58 -Tyr 59 -Ser 60 -Gln 61 -Val 62 -Leu 63 -Phe 64 -Lys 65 -Gly 66 -Gln 67 -Gly 68 -Cys 69 -Pro 70 -Ser 71 -Thr 72 -His 73 -Val 74 -Leu 75 -Leu 76 -Thr 77 -His 78 -Thr 79 ), 110-127 (Glu 110 -Ala 111 -Lys 112 -Pro 113 -Trp 114 -Tyr 115 -Glu 116 -Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 -Leu 126 -Glu 127 ) and 135-155 (Glu 135 -Ile 136 -Asn 137 -Arg 138 -Pro 139 -Asp 140 -Tyr 141 -Leu 142 -Asp 143 -Phe 144 -Ala 145 -Glu 146 -Ser 147 -Gly 148 -Gln 149 -Val 150 -Tyr 151 -Phe 152 -Gly 153 -Ile 154 -Ile 155 ), or the topographic region of residues 1-30 (Val 1 -Arg 2 -Ser 3 -Ser 4 -Ser 5 -Arg 6 -Thr 7 -Pro 8 -Ser 9 -Asp 10 -Lys 11 -Pro 12 -Val 13 -Ala 14 -His 15 -Val 16 -Val 17 -Ala 18 -Asn 19 -Pro 20 Gln 21 Ala 22 -Glu 23 -Gly 24 -Gln 25 -Leu 26 -Gln 27 -Trp 28 -Leu 29 -Asn 30 ), 117-128 (Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 -Leu 126 -Glu 127 -Lys 128 ) and 141-153 (Tyr 141 -Leu 142 -Asp 143 -Phe 144 -Ala 145 -Glu 146 -Ser 147 -Gly 148 -Gln 149 -Val 150 -Tyr 151 -Phe 152 -Gly 153 ), or the topographic region of residues 22-40 (Ala 22 -Glu 23 -Gly 24 -Gln 25 -Leu 26 -Gln 27 -Trp 28 -Leu 29 -Asn 30 -Arg 31 -Arg 32 -Ala 33 -Asn 34 -Ala 35 -Leu 36 -Leu 37 -Ala 38 -Asn 39 -Gly 40 ), 49-97 (Val 49 -Val 50 -Pro 51 -Ser 52 -Glu 53 -Gly 54 -Leu 55 -Tyr 56 -Leu 57 -Ile 58 -Tyr 59 -Ser 60 -Gln 61 -Val 62 -Leu 63 -Phe 64 -Lys 65 -Gly 66 -Gln 67 -Gly 68 -Cys 69 -Pro 70 -Ser 71 -Thr 72 -His 73 -Val 74 -Leu 75 -Leu 76 -Thr 77 -His 78 -Thr 79 -Ile 80 -Ser 81 -Arg 82 -Ile 83 -Ala 84 -Val 85 -Ser 86 -Tyr 87 -Gln 88 -Thr 89 -Lys 90 -Val 91 -Asn 92 -Leu 93 -Leu 94 -Ser 95 -Ala 96 -Ile 97 ), 110-127 (Glu 110 -Ala 111 -Lys 112 -Pro 113 -Trp 114 -Tyr 115 -Glu 116 -Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 -Leu 126 -Glu 127 ) and 136-153 (Ile 136 -Asn 137 -Arg 138 -Pro 139 -Asp 140 -Tyr 141 -Leu 142 -Asp 143 -Phe 144 -Ala 145 -Glu 146 -Ser 147 -Gly 148 -Gln 149 -Val 150 -Tyr 151 -Phe 152 -Gly 153 ), or the topographic region of residues 1-20 (Val 1 -Arg 2 -Ser 3 -Ser 4 -Ser 5 -Arg 6 -Thr 7 -Pro 8 -Ser 9 -Asp 10 -Lys 11 -Pro 12 -Val 13 -Ala 14 -His 15 -Val 16 -Val 17 -Ala 18 -Asn 19 -Pro 20 ) and 76-90 (Leu 76 -Thr 77 -His 78 -Thr 79 -Ile 80 -Ser 81 -Arg 82 -Ile 83 -Ala 84 -Val 85 -Ser 86 -Tyr 87 -Gln 88 -Thr 89 -Lys 90 ), or the topographic region of residues 22-40 (Ala 22 -Glu 23 -Gly 24 -Gln 25 -Leu 26 -Gln 27 -Trp 28 -Leu 29 -Asn 30 -Arg 31 -Arg 32 -Ala 33 -Asn 34 -Ala 35 -Leu 36 -Leu 37 -Ala 38 -Asn 39 -Gly 40 ), 69-97 (Cys 69 -Pro 70 -Ser 71 -Thr 72 -His 73 -Val 74 -Leu 75 -Leu 76 -Thr 77 -His 78 -Thr 79 -Ile 80 -Ser 81 -Arg 82 -Ile 83 -Ala 84 -Val 85 -Ser 86 -Tyr 87 -Gln 88 -Thr 89 -Lys 90 -Val 91 -Asn 92 -Leu 93 -Leu 94 -Ser 95 -Ala 96 -Ile 97 ), 105-128 (Thr 105 -Pro 106 -Glu 107 -Gly 108 -Ala 109 -Glu 110 -Ala 111 -Lys 112 -Pro 113 -Trp 114 -Tyr 115 -Glu 116 -Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 -Leu 126 -Glu 127 -Lys 128 ) and 135-155 (Glu 135 -Ile 136 -Asn 137 -Arg 138 -Pro 139 -Asp 140 -Tyr 141 -Leu 142 -Asp 143 -Phe 144 -Ala 145 -Glu 146 -Ser 147 -Gly 148 -Gln 149 -Val 150 -Tyr 151 -Phe 152 -Gly 153 -Ile 154 -Ile 155 ) is prevented from binding to mature human TNF-α receptor.    
     
     
         20 . An isolated single chain antibody according to  claim 19 , 
 wherein the antibody binds to TNF-α such that the epitope defined by the topographic regions of 1-18 (Val 1 -Arg 2 -Ser 3 -Ser 4 -Ser 5 -Arg 6 -Thr 7 -Pro 8 -Ser 9 -Asp 10 -Lys 11 -Pro 12 -Val 13 -Ala 14 -His 15 -Val 16 -Val 17 -Ala 18 ), 58-65 (Ile 58 -Tyr 59 -Ser 60 -Gln 61 -Val 62 -Leu 63 -Phe 64 -Lys 65 ), 115-125 (Tyr 115 -Glu 116 -Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 ) and 138-149 (Arg 138 -Pro 139 -Asp 140 -Tyr 141 -Leu 142 -Asp 143 -Phe 144 -Ala 145 -Glu 146 -Ser 147 -Gly 148 -Gln 149 ), or the topographic region of residues 1-18 (Val 1 -Arg 2 -Ser 3 -Ser 4 -Ser 5 -Arg 6 -Thr 7 -Pro 8 -Ser 9 -Asp 10 -Lys 11 -Pro 12 -Val 13 -Ala 14 -His 15 -Val 16 -Val 17 -Ala 18 ) and 108-128 (Gly 108 -Ala 109 -Glu 110 -Ala 111 -Lys 112 -Pro 113 -Trp 114 -Tyr 115 -Glu 116 -Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 -Leu 126 -Glu 127 -Lys 128 ), or the topographic region of residues 56-79 (Tyr 56 -Leu 57 -Ile 58 -Tyr 59 -Ser 60 -Gln 61 -Val 62 -Leu 63 -Phe 64 -Lys 65 -Gly 66 -Gln 67 -Gly 68 -Cys 69 -Pro 70 -Ser 71 -Thr 72 -His 73 -Val 74 -Leu 75 -Leu 76 -Thr 77 -His 78 -Thr 79 ), 110-127 (Glu 110 -Ala 111 -Lys 112 -Pro 113 -Trp 114 -Tyr 115 -Glu 116 -Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 -Leu 126 -Glu 127 ) and 135-155 (Glu 135 -Ile 136 -Asn 137 -Arg 138 -Pro 139 -Asp 140 -Tyr 141 -Leu 142 -Asp 143 -Phe 144 -Ala 145 -Glu 146 -Ser 147 -Gly 148 -Gln 149 -Val 150 -Tyr 151 -Phe 152 -Gly 153 -Ile 154 -Ile 155 ), or the topographic region of residues 1-20 (Val 1 -Arg 2 -Ser 3 -Ser 4 -Ser 5 -Arg 6 -Thr 7 -Pro 8 -Ser 9 -Asp 10 -Lys 11 -Pro 12 -Val 13 -Ala 14 -His 15 -Val 16 -Val 17 -Ala 18 -Asn 19 -Pro 20 ) and 76-90 (Leu 76 -Thr 77 -His 78 -Thr 79 -Ile 80 -Ser 81 -Arg 82 -Ile 83 -Ala 84 -Val 85 -Ser 86 -Tyr 87 -Gln 88 -Thr 89 -Lys 90 ), or the topographic region of residues 22-40 (Ala 22 -Glu 23 -Gly 24 -Gln 25 -Leu 26 -Gln 27 -Trp 28 -Leu 29 -Asn 30 -Arg 31 -Arg 32 -Ala 33 -Asn 34 -Ala 35 -Leu 36 -Leu 37 -Ala 38 -Asn 39 -Gly 40 ), 69-97 (Cys 69 -Pro 70 -Ser 71 -Thr 72 -His 73 -Val 74 -Leu 75 -Leu 76 -Thr 77 -His 78 -Thr 79 -Ile 80 -Ser 81 -Arg 82 -Ile 83 -Ala 84 -Val 85 -Ser 86 -Tyr 87 -Gln 88 -Thr 89 -Lys 90 -Val 91 -Asn 92 -Leu 93 -Leu 94 -Ser 95 -Ala 96 -Ile 97 ), 105-128 (Thr 105 -Pro 106 -Glu 107 -Gly 108 -Ala 109 -Glu 110 -Ala 111 -Lys 112 -Pro 113 -Trp 114 -Tyr 115 -Glu 116 -Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 -Leu 126 -Glu 127 -Lys 128 ) and 135-155 (Glu 135 -Ile 136 -Asn 137 -Arg 138 -Pro 139 -Asp 140 -Tyr 141 -Leu 142 -Asp 143 -Phe 144 -Ala 145 -Glu 146 -Ser 147 -Gly 148 -Gln 149 -Val 150 -Tyr 151 -Phe 152 -Gly 153 -Ile 154 -Ile 155 ) is prevented from binding to mature human TNF-α receptor, and    wherein the antibody inhibits cytotoxicity.    
     
     
         21 . An isolated single chain antibody according to  claim 19 , 
 wherein the antibody binds to TNF-α such that the epitope defined by the topographic regions of 1-18 (Val 1 -Arg 2 -Ser 3 -Ser 4 -Ser 5 -Arg 6 -Thr 7 -Pro 8 -Ser 9 -Asp 10 -Lys 11 -Pro 12 -Val 13 -Ala 14 -His 15 -Val 16 -Val 17 -Ala 18 ), 58-65 (Ile 58 -Tyr 59 -Ser 60 -Gln 61 -Val 62 -Leu 63 -Phe 64 -Lys 65 ), 115-125 (Tyr 115 -Glu 116 -Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 ) and 138-149 (Arg 138 -Pro 139 -Asp 140 -Tyr 141 -Leu 142 -Asp 143 -Phe 144 -Ala 145 -Glu 146 -Ser 147 -Gly 148 -Gln 149 ), or the topographic region of residues 1-18 (Val 1 -Arg 2 -Ser 3 -Ser 4 -Ser 5 -Arg 6 -Thr 7 -Pro 8 -Ser 9 -Asp 10 -Lys 11 -Pro 12 -Val 13 -Ala 14 -His 15 -Val 16 -Val 17 -Ala 18 ) and 108-128 (Gly 108 -Ala 109 -Glu 110 -Ala 111 -Lys 112 -Pro 113 -Trp 114 -Tyr 115 -Glu 116 -Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 -Leu 126 -Glu 127 -Lys 128 ), or the topographic region of residues 56-79 (Tyr 56 -Leu 57 -Ile 58 -Tyr 59 -Ser 60 -Gln 61 -Val 62 -Leu 63 -Phe 64 -Lys 65 -Gly 66 -Gln 67 -Gly 68 -Cys 69 -Pro 70 -Ser 71 -Thr 72 -His 73 -Val 74 -Leu 7 5-Leu 76 -Thr 77 -His 78 -Thr 79 ), 110-127 (Glu 110 -Ala 111 -Lys 112 -Pro 113 -Trp 114 -Tyr 115 -Glu 116 -Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 -Leu 126 -Glu 127 ) and 135-155 (Glu 135 -Ile 136 -Asn 137 -Arg 138 -Pro 139 -Asp 140 -Tyr 141 -Leu 142 -Asp 143 -Phe 144 -Ala 145 -Glu 146 -Ser 147 -Gly 148 -Gln 149 -Val 150-Tyr 151 -Phe 152 -Gly 153 -Ile 154 -Ile 155 ), or the topographic region of residues 1-20 (Val 1 -Arg 2 -Ser 3 -Ser 4 -Ser 5 -Arg 6 -Thr 7 -Pro 8 -Ser 9 -Asp 10 -Lys 11 -Pro 2 -Val 3 -Ala 14 -His 5-Val 16 -Val 17 -Ala 18 -Asn 19 -Pro 20 ) and 76-90 (Leu 76 -Thr 77 -His 78 -Thr 79 -Ile 80 -Ser 81 -Arg 82 -Ile 83 -Ala 84 -Val 85 -Ser 86 -Tyr 87 -Gln 88 -Thr 89 -Lys 90 ), or the topographic region of residues 22-40 (Ala 22 -Glu 23 -Gly 24 -Gln 25 -Leu 26 -Gln 27 -Trp 28 -Leu 29 -Asn 30 -Arg 31 -Arg 32 -Ala 33 -Asn 34 -Ala 35 -Leu 36 -Leu 37 -Ala 38 -Asn 39 -Gly 40 ), 69-97 (Cys 69 -Pro 70 -Ser 71 -Thr 72 -His 73 -Val 74 -Leu 75 -Leu 76 -Thr 77 -His 78 -Thr 79 -Ile 80 -Ser 81 -Arg 82 -Ile 83 -Ala 84 -Val 85 -Ser 86 -Tyr 87 -Gln 88 -Thr 89 -Lys 90 -Val 91 -Asn 92 -Leu 93 -Leu 94 -Ser 95 -Ala 96 -Ile 97 ), 105-128 (Thr 105 -Pro 106 -Glu 107 -Gly 108 -Ala 109 -Glu 110 -Ala 111 -Lys 112 -Pro 113 -Trp 114 -Tyr 115 -Glu 116 -Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 -Leu 126 -Glu 127 -Lys 128 ) and 135-155 (Glu 135 -Ile 136 -Asn 137 -Arg 138 -Pro 139 -Asp 140 -Tyr 141 -Leu 142 -Asp 143 -Phe 144 -Ala 145 -Glu 146 -Ser 147 -Gly 148 -Gln 149 -Val 150 -Tyr 151 -Phe 152 -Gly 153 -Ile 154 -Ile 155 ) is prevented from binding to mature human TNF-α receptor, and    wherein the antibody inhibits tumor regression.    
     
     
         22 . An isolated single chain antibody according to  claim 19 , 
 wherein the antibody binds to TNF-α such that the epitope defined by the topographic regions of wherein the antibody binds to TNF-α such that the epitope defined by the topographic region of residues 1-30 (Val 1 -Arg 2 -Ser 3 -Ser 4 -Ser 5 -Arg 6 -Thr 7 -Pro 8 -Ser 9 -Asp 10 -Lys 11 -Pro 12 -Val 13 -Ala 14 -His 15 -Val 16 -Val 17 -Ala 18 -Asn 19 -Pro 20 Gln 21  Ala 22 -Glu 23 -Gly 24 -Gln 25 -Leu 26 -Gln 27 -Trp 28 -Leu 29 -Asn 30 ), 117-128 (Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 -Leu 126 -Glu 127 -Lys 128 ) and 141-153 (Tyr 141 -Leu 142 -Asp 143 -Phe 144 -Ala 145 -Glu 146 -Ser 147 -Gly 148 -Gln 149 -Val 150 -Tyr 151 -Phe 152 -Gly 153 ) or the topographic region of residues 22-40 (Ala 22 -Glu 23 -Gly 24 -Gln 25 -Leu 26 -Gln 27 -Trp 28 -Leu 29 -Asn 30 -Arg 31 -Arg 32 -Ala 33 -Asn 34 -Ala 35 -Leu 36 -Leu 37 -Ala 38 -Asn 39 -Gly 40 ), 49-97 (Val 49 -Val 50 -Pro 51 -Ser 52 -Glu 53 -Gly 54 -Leu 55 -Tyr 56 -Leu 57 -Ile 58 -Tyr 59 -Ser 60 -Gln 61 -Val 62 -Leu 63 -Phe 64 -Lys 65 -Gly 66 -Gln 67 -Gly 68 -Cys 69 -Pro 70 -Ser 71 -Thr 72 -His 73 -Val 74 -Leu 75 -Leu 76 -Thr 77 -His 78 -Thr 79 -Ile 80 -Ser 81 -Arg 82 -Ile 83 -Ala 84 -Val 85 -Ser 86 -Tyr 87 -Gln 88 -Thr 89 -Lys 90 -Val 91 -Asn 92 -Leu 93 -Leu 94 -Ser 95 -Ala 96 -Ile 97 ), 110-127 (Glu 110 -Ala 111 -Lys 112 -Pro 113 -Trp 114 -Tyr 115 -Glu 116 -Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 -Leu 126 -Glu 127 ) and 136-153 (Ile 136 -Asn 137 -Arg 138 -Pro 139 -Asp 140 -Tyr 141 -Leu 142 -Asp 143 -Phe 144 -Ala 145 -Glu 146 -Ser 147 -Gly 148 -Gln 149 -Val 150 -Tyr 151 -Phe 152 -Gly 153 ) is prevented from binding to mature human TNF-α receptor and    wherein the antibody has no effect on cytotoxicity.    
     
     
         23 . An isolated single chain antibody according to any one of claims  19 - 22 , wherein the antibody is a humanized antibody.  
     
     
         24 . An isolated single chain antibody according to any one of claims  19 - 22 , wherein the antibody is a chimeric antibody.  
     
     
         25 . An isolated single chain antibody according to any one of claims  19 - 22 , wherein the antibody is a human antibody.  
     
     
         26 . A composition comprising an isolated single chain antibody that binds to mature human TNF-α, 
 wherein the antibody is characterized in that when the antibody binds to TNF-α the induction of endothelial procoagulant activity is inhibited,    wherein the antibody binds to TNF-α such that the epitope defined by the topographic regions of 1-18 (Val 1 -Arg 2 -Ser 3 -Ser 4 -Ser 5 -Arg 6 -Thr 7 -Pro 8 -Ser 9 -Asp 10 -Lys 11 -Pro 12 -Val 13 -Ala 14 -His 15 -Val 16 -Val 17 -Ala 18 ), 58-65 (Ile 58 -Tyr 59 -Ser 60 -Gln 61 -Val 62 -Leu 63 -Phe 64 -Lys 65 ), 115-125 (Tyr 115 -Glu 116 -Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 ) and 138-149 (Arg 138 -Pro 139 -Asp 140 -Tyr 141 -Leu 142 -Asp 143 -Phe 144 -Ala 145 -Glu 146 -Ser 147 -Gly 148 -Gln 149 ), or the topographic region of residues 1-18 (Val 1 -Arg 2 -Ser 3 -Ser 4 -Ser 5 -Arg 6 -Thr 7 -Pro 8 -Ser 9 -Asp 10 -Lys 11 -Pro 12 -Val 13 -Ala 14 -His 15 -Val 16 -Val 17 -Ala 18 ) and 108-128 (Gly 108 -Ala 109 -Glu 110 -Ala 111 -Lys 112 -Pro 113 -Trp 114 -Tyr 115 -Glu 116 -Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 -Leu 126 -Glu 127 -Lys 128 ), or the topographic region of residues 56-79 (Tyr 56 -Leu 57 -Ile 58 -Tyr 59 -Ser 60 -Gln 61 -Val 62 -Leu 63 -Phe 64 -Lys 65 -Gly 66 -Gln 67 -Gly 68 -Cys 69 -Pro 70 -Ser 71 -Thr 72 -His 73 -Val 74 -Leu 75 -Leu 76 -Thr 77 -His 78 -Thr 79 ), 110-127 (Glu 110 -Ala 111 -Lys 112 -Pro 113 -Trp 114 -Tyr 115 -Glu 116 -Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 -Leu 126 -Glu 127 ) and 135-155 (Glu 135 -Ile 136 -Asn 137 -Arg 138 -Pro 139 -Asp 140 -Tyr 141 -Leu 142 -Asp 143 -Phe 144 -Ala 145 -Glu 146 -Ser 147 -Gly 148 -Gln 149 -Val 150 -Tyr 151 -Phe 152 -Gly 153 -Ile 154 -Ile 155 ), or the topographic region of residues 1-30 (Val 1 -Arg 2 -Ser 3 -Ser 4 -Ser 5 -Arg 6 -Thr 7 -Pro 8 -Ser 9 -Asp 10 -Lys 11 -Pro 12 -Val 13 -Ala 14 -His 15 -Val 16 -Val 17 -Ala 18 -Asn 19 -Pro 20 Gln 21 Ala 22 -Glu 23 -Gly 24 -Gln 25 -Leu 26 -Gln 27 -Trp 28 -Leu 29 -Asn 30 ), 117-128 (Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 -Leu 126 -Glu 127 -Lys 128 ) and 141-153 (Tyr 141 -Leu 142 -Asp 143 -Phe 144 -Ala 145 -Glu 146 -Ser 147 -Gly 148 -Gln 149 -Val 150 -Tyr 151 -Phe 152 -Gly 153 ), or the topographic region of residues 22-40 (Ala 22 -Glu 23 -Gly 24 -Gln 25 -Leu 26 -Gln 27 -Trp 28 -Leu 29 -Asn 30 -Arg 31 -Arg 32 -Ala 33 -Asn 34 -Ala 35 -Leu 36 -Leu 37 -Ala 38 -Asn 39 -Gly 40 ), 49-97 (Val 49 -Val 50 -Pro 51 -Ser 52 -Glu 53 -Gly 54 -Leu 55 -Tyr 56 -Leu 57 -Ile 58 -Tyr 59 -Ser 60 -Gln 61 -Val 62 -Leu 63 -Phe 64 -Lys 65 -Gly 66 -Gln 67 -Gly 68 -Cys 69 -Pro 70 -Ser 71 -Thr 72 -His 73 -Val 74 -Leu 75 -Leu 76 -Thr 77 -His 78 -Thr 79 -Ile 80 -Ser 81 -Arg 82 -Ile 83 -Ala 84 -Val 85 -Ser 86 -Tyr 87 -Gln 88 -Thr 89 -Lys 90 -Val 91 -Asn 92 -Leu 93 -Leu 94 -Ser 95 -Ala 96 -Ile 97 ), 110-127 (Glu 110 -Ala 111 -Lys 112 -Pro 113 -Trp 114 -Tyr 115 -Glu 116 -Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 -Leu 126 -Glu 127 ) and 136-153 (Ile 136 -Asn 137 -Arg 138 -Pro 139 -Asp 140 -Tyr 141 -Leu 142 -Asp 143 -Phe 144 -Ala 145 -Glu 146 -Ser 147 -Gly 148 -Gln 149 -Val 150 -Tyr 151 -Phe 152 -Gly 153 ), or the topographic region of residues 1-20 (Val 1 -Arg 2 -Ser 3 -Ser 4 -Ser 5 -Arg 6 -Thr 7 -Pro 8 -Ser 9 -Asp 10 -Lys 11 -Pro 2 -Val 3 -Ala 14 -His 15 -Val 16 -Val 17 -Ala 18 -Asn 19 -Pro 20 ) and 76-90 (Leu 76 -Thr 77 -His 78 -Thr 79 -Ile 80 -Ser 81 -Arg 82 -Ile 83 -Ala 84 -Val 85 -Ser 86 -Tyr 87 -Gln 88 -Thr 89 -Lys 90 ), or the topographic region of residues 22-40 (Ala 22 -Glu 23 -Gly 24 -Gln 25 -Leu 26 -Gln 27 -Trp 28 -Leu 29 -Asn 30 -Arg 31 -Arg 32 -Ala 33 -Asn 34 -Ala 35 -Leu 36 -Leu 37 -Ala 38 -Asn 39 -Gly 40 ), 69-97 (Cys 69 -Pro 70 -Ser 71 -Thr 72 -His 73 -Val 74 -Leu 75 -Leu 76 -Thr 77 -His 78 -Thr 79 -Ile 80 -Ser 81 -Arg 82 -Ile 83 -Ala 84 -Val 85 -Ser 86 -Tyr 87 -Gln 88 -Thr 89 -Lys 90 -Val 91 -Asn 92 -Leu 93 -Leu 94 -Ser 95 -Ala 96 -Ile 97 ), 105-128 (Thr 105 -Pro 106 -Glu 107 -Gly 108 -Ala 109 -Glu 110 -Ala 111 -Lys 112 -Pro 113 -Trp 114 -Tyr 115 -Glu 116 -Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 -Leu 126 -Glu 127 -Lys 128 ) and 135-155 (Glu 135 -Ile 136 -Asn 137 -Arg 138 -Pro 139 -Asp 140 -Tyr 141 -Leu 142 -Asp 143 -Phe 144 -Ala 145 -Glu 146 -Ser 147 -Gly 148 -Gln 149 -Val 150 -Tyr 151 -Phe 152 -Gly 153 -Ile 154 -Ile 155 ) is prevented from binding to mature human TNF-α receptor.    
     
     
         27 . A composition according to  claim 26 , 
 wherein the antibody binds to TNF-α such that the epitope defined by the topographic regions of 1-18 (Val 1 -Arg 2 -Ser 3 -Ser 4 -Ser 5 -Arg 6 -Thr 7 -Pro 8 -Ser 9 -Asp 10 -Lys 11 -Pro 12 -Val 13 -Ala 14 -His 15 -Val 16 -Val 17 -Ala 18 ), 58-65 (Ile 58 -Tyr 59 -Ser 60 -Gln 61 -Val 62 -Leu 63 -Phe 64 -Lys 65 ), 115-125 (Tyr 115 -Glu 116 -Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 ) and 138-149 (Arg 138 -Pro 139 -Asp 140 -Tyr 141 -Leu 142 -Asp 143 -Phe 144 -Ala 145 -Glu 146 -Ser 147 -Gly 148 -Gln 149 ), or the topographic region of residues 1-18 (Val 1 -Arg 2 -Ser 3 -Ser 4 -Ser 5 -Arg 6 -Thr 7 -Pro 8 -Ser 9 -Asp 10 -Lys 11 -Pro 12 -Val 13 -Ala 14 -His 15 -Val 16 -Val 17 -Ala 18 ) and 108-128 (Gly 108 -Ala 109 -Glu 110 -Ala 111 -Lys 112 -Pro 113 -Trp 114 -Tyr 115 -Glu 116 -Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 -Leu 126 -Glu 127 -Lys 128 ), or the topographic region of residues 56-79 (Tyr 56 -Leu 57 -Ile 58 -Tyr 59 -Ser 60 -Gln 61 -Val 62 -Leu 63 -Phe 64 -Lys 65 -Gly 66 -Gln 67 -Gly 68 -Cys 69 -Pro 70 -Ser 71 -Thr 72 -His 73 -Val 74 -Leu 75 -Leu 76 -Thr 77 -His 78 -Thr 79 ), 110-127 (Glu 110 -Ala 111 -Lys 112 -Pro 113 -Trp 114 -Tyr 115 -Glu 116 -Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 -Leu 126 -Glu 127 ) and 135-155 (Glu 135 -Ile 136 -Asn 137 -Arg 138 -Pro 139 -Asp 140 -Tyr 141 -Leu 142 -Asp 143 -Phe 144 -Ala 145 -Glu 146 -Ser 147 -Gly 148 -Gln 149 -Val 150 -Tyr 151 -Phe 152 -Gly 153 -Ile 154 -Ile 155 ), or the topographic region of residues 1-20 (Val 1 -Arg 2 -Ser 3 -Ser 4 -Ser 5 -Arg 6 -Thr 7 -Pro 8 -Ser 9 -Asp 10 -Lys 11 -Pro 12 -Val 13 -Ala 14 -His 15 -Val 16 -Val 17 -Ala 18 -Asn 19 -Pro 20 ) and 76-90 (Leu 76 -Thr 77 -His 78 -Thr 79 -Ile 80 -Ser 81 -Arg 82 -Ile 83 -Ala 84 -Val 85 -Ser 86 -Tyr 87 -Gln 88 -Thr 89 -Lys 90 ), or the topographic region of residues 22-40 (Ala 22 -Glu 23 -Gly 24 -Gln 25 -Leu 26 -Gln 27 -Trp 28 -Leu 29 -Asn 30 -Arg 31 -Arg 32 -Ala 33 -Asn 34 -Ala 35 -Leu 36 -Leu 37 -Ala 38 -Asn 39 -Gly 40 ), 69-97 (Cys 69 -Pro 70 -Ser 71 -Thr 72 -His 73 -Val 74 -Leu 75 -Leu 7 6-Thr 77 -His 78 -Thr 79 -Ile 80 -Ser 81 -Arg 82 -Ile 83 -Ala 84 -Val 85 -Ser 86 -Tyr 87 -Gln 88 -Thr 89 -Lys 90 -Val 91 -Asn 92 -Leu 93 -Leu 94 -Ser 95 -Ala 96 -Ile 97 ), 105-128 (Thr 105 -Pro 106 -Glu 107 -Gly 108 -Ala 109 -Glu 110 -Ala 111 -Lys 112 -Pro 113 -Trp 114 -Tyr 115 -Glu 116 -Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 -Leu 126 -Glu 127 -Lys 128 ) and 135-155 (Glu 135 -Ile 136 -Asn 137 -Arg 138 -Pro 139 -Asp 140 -Tyr 141 -Leu 142 -Asp 143 -Phe 144 -Ala 145 -Glu 146 -Ser 147 -Gly 148 -Gln 149 -Val 150 -Tyr 151 -Phe 152 -Gly 153 -Ile 154 -Ile 155 ) is prevented from binding to mature human TNF-α receptor, and    wherein the antibody inhibits cytotoxicity.    
     
     
         28 . A composition according to  claim 26 , 
 wherein the antibody binds to TNF-α such that the epitope defined by the topographic regions of 1-18 (Val 1 -Arg 2 -Ser 3 -Ser 4 -Ser 5 -Arg 6 -Thr 7 -Pro 8  Ser 9 -Asp 10 -Lys 11 -Pro 12 -Val 13 -Ala 14 -His 15 -Val 16 -Val 17 -Ala 18 ), 58-65 (Ile 58 -Tyr 59 -Ser 60 -Gln 61 -Val 62 -Leu 63 -Phe 64 -Lys 65 ), 115-125 (Tyr 115 -Glu 116 -Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 ) and 138-149 (Arg 138 -Pro 139 -Asp 140 -Tyr 141 -Leu 142 -Asp 143 -Phe 144 -Ala 145 -Glu 146 -Ser 147 -Gly 148 -Gln 149 ), or the topographic region of residues 1-18 (Val 1 -Arg 2 -Ser 3 -Ser 4 -Ser 5 -Arg 6 -Thr 7 -Pro 8 -Ser 9 -Asp 10 -Lys 11 -Pro 12 -Val 13 -Ala 14 -His 15 -Val 16 -Val 17 -Ala 18 ) and 108-128 (Gly 108 -Ala 109 -Glu 110 -Ala 111 -Lys 112 -Pro 113 -Trp 114 -Tyr 115 -Glu 116 -Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 -Leu 126 -Glu 127 -Lys 128 ), or the topographic region of residues 56-79 (Tyr 56 -Leu 57 -Ile 58 -Tyr 59 -Ser 60 -Gln 61 -Val 62 -Leu 63 -Phe 64 -Lys 65 -Gly 66 -Gln 67 -Gly 68 -Cys 69 -Pro 70 -Ser 71 -Thr 72 -His 73 -Val 74 -Leu 75 -Leu 76 -Thr 77 -His 78 -Thr 79 ), 110-127 (Glu 110 -Ala 111 -Lys 112 -Pro 113 -Trp 114 -Tyr 115 -Glu 116 -Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 -Leu 126 -Glu 127 ) and 135-155 (Glu 135 -Ile 136 -Asn 137 -Arg 138 -Pro 139 -Asp 140 -Tyr 141 -Leu 142 -Asp 143 -Phe 144 -Ala 145 -Glu 146 -Ser 147 -Gly 148 -Gln 149 -Val 150 -Tyr 151 -Phe 152 -Gly 153 -Ile 154 -Ile 155 ), or the topographic region of residues 1-20 (Val 1 -Arg 2 -Ser 3 -Ser 4 -Ser 5 -Arg 6 -Thr 7 -Pro 8 -Ser 9 -Asp 10 -Lys 11 -Pro 12 -Val 13 -Ala 14 -His 15 -Val 16 -Val 17 -Ala 18 -Asn 19 -Pro 20 ) and 76-90 (Leu 76 -Thr 77 -His 78 -Thr 79 -Ile 80 -Ser 81 -Arg 82 -Ile 83 -Ala 84 -Val 85 -Ser 86 -Tyr 87 -Gln 88 -Thr 89 -Lys 90 ), or the topographic region of residues 22-40 (Ala 22 -Glu 23 -Gly 24 -Gln 25 -Leu 26 -Gln 27 -Trp 28 -Leu 29 -Asn 30 -Arg 31 -Arg 32 -Ala 33 -Asn 34 -Ala 35 -Leu 36 -Leu 37 -Ala 38 -Asn 39 -Gly 40 ), 69-97 (Cys 69 -Pro 70 -Ser 71 -Thr 72 -His 73 -Val 74 -Leu 75 -Leu 76 -Thr 77 -His 78 -Thr 79 -Ile 80 -Ser 81 -Arg 82 -Ile 83 -Ala 84 -Val 85 -Ser 86 -Tyr 87 -Gln 88 -Thr 89 -Lys 90 -Val 91 -Asn 92 -Leu 93 -Leu 94 -Ser 95 -Ala 96 -Ile 97 ), 105-128 (Thr 105 -Pro 106 -Glu 107 -Gly 108 -Ala 109 -Glu 110 -Ala 111 -Lys 112 -Pro 113 -Trp 114 -Tyr 115 -Glu 116 -Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 -Leu 126 -Glu 127 -Lys 128 ) and 135-155 (Glu 135 -Ile 136 -Asn 137 -Arg 138 -Pro 139 -Asp 140 -Tyr 141 -Leu 142 -Asp 143 -Phe 144 -Ala 145 -Glu 146 -Ser 147 -Gly 148 -Gln 149 -Val 150 -Tyr 151 -Phe 152 -Gly 153 -Ile 154 -Ile 155 ), and    wherein the antibody inhibits tumor regression.    
     
     
         29 . A composition according to  claim 26 , 
 wherein the antibody binds to TNF-α such that the epitope defined by the topographic regions of wherein the antibody binds to TNF-α such that the epitope defined by the topographic region of residues 1-30 (Val 1 -Arg 2 -Ser 3 -Ser 4 -Ser 5 -Arg 6 -Thr 7 -Pro 8 -Ser 9 -Asp 10 -Lys 11 -Pro 12 -Val 13 -Ala 14 -His 15 -Val 16 -Val 17 -Ala 18 -Asn 19 -Pro 20 Gln 21 Ala 22 -Glu 23 -Gly 24 -Gln 25 -Leu 26 -Gln 27 -Trp 28 -Leu 29 -Asn 30 ), 117-128 (Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 -Leu 126 -Glu 127 -Lys 128 ) and 141-153 (Tyr 141 -Leu 142 -Asp 143 -Phe 144 -Ala 145 -Glu 146 -Ser 147 -Gly 148 -Gln 149 -Val 150 -Tyr 151 -Phe 152 -Gly 153 ), or the topographic region of residues 22-40 (Ala 22 -Glu 23 -Gly 24 -Gln 25 -Leu 26 -Gln 27 -Trp 28 -Leu 29 -Asn 30 -Arg 31 -Arg 32 -Ala 33 -Asn 34 -Ala 35 -Leu 36 -Leu 37 -Ala 38 -Asn 39 -Gly 40 ), 49-97 (Val 49 -Val 50 -Pro 51 -Ser 52 -Glu 53 -Gly 54 -Leu 55 -Tyr 56 -Leu 57 -Ile 58 -Tyr 59 -Ser 60 -Gln 61 -Val 62 -Leu 63 -Phe 64 -Lys 65 -Gly 66 -Gln 67 -Gly 68 -Cys 69 -Pro 70 -Ser 71 -Thr 72 -His 73 -Val 74 -Leu 75 -Leu 76 -Thr 77 -His 78 -Thr 79 -Ile 80 -Ser 81 -Arg 82 -Ile 83 -Ala 84 -Val 85 -Ser 86 -Tyr 87 -Gln 88 -Thr 89 -Lys 90 -Val 91 -Asn 92 -Leu 93 -Leu 94 -Ser 95 -Ala 96 -Ile 97 ), 110-127 (Glu 110 -Ala 111 -Lys 112 -Pro 113 -Trp 114 -Tyr 115 -Glu 116 -Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 -Leu 126 -Glu 127 ) and 136-153 (Ile 136 -Asn 137 -Arg 138 -Pro 139 -Asp 140 -Tyr 141 -Leu 142 -Asp 143 -Phe 144 -Ala 145 -Glu 146 -Ser 147 -Gly 148 -Gln 149 -Val 150 -Tyr 151 -Phe 152 -Gly 153 ) is prevented from binding to mature human TNF-α receptor and    wherein the antibody has no effect on cytotoxicity.    
     
     
         30 . A composition according to any one of claims  26 - 29 , wherein the antibody is a humanized antibody.  
     
     
         31 . A composition according to any one of claims  26 - 29 , wherein the antibody is a chimeric antibody.  
     
     
         32 . A composition according to any one of claims  26 - 29 , wherein the antibody is a human antibody.  
     
     
         33 . An isolated single domain antibody or fragment thereof that specifically binds to mature human TNF-α, 
 wherein the antibody is characterized in that when the antibody binds to TNF-α the induction of endothelial procoagulant activity is inhibited,    wherein the antibody binds to TNF-α such that the epitope defined by the topographic regions of 1-18 (Val 1 -Arg 2 -Ser 3 -Ser 4 -Ser 5 -Arg 6 -Thr 7 -Pro 8 -Ser 9 -Asp 10 -Lys 11 -Pro 12 -Val 13 -Ala 14 -His 15 -Val 16 -Val 17 -Ala 18 ), 58-65 (Ile 58 -Tyr 59 -Ser 60 -Gln 61 -Val 62 -Leu 63 -Phe 64 -Lys 65 ), 115-125 (Tyr 115 -Glu 116 -Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 ) and 138-149 (Arg 138 -Pro 139 -Asp 140 -Tyr 141 -Leu 142 -Asp 143 -Phe 144 -Ala 145 -Glu 146 -Ser 147 -Gly 148 -Gln 149 ), or the topographic region of residues 1-18 (Val 1 -Arg 2 -Ser 3 -Ser 4 -Ser 5 -Arg 6 -Thr 7 -Pro 8 -Ser 9 -Asp 10 -Lys 11 -Pro 12 -Val 13 -Ala 14 -His 15 -Val 16 -Val 17 -Ala 18 ) and 108-128 (Gly 108 -Ala 109 -Glu 110 -Ala 111 -Lys 112 -Pro 113 -Trp 114 -Tyr 115 -Glu 116 -Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 -Leu 126 -Glu 127 -Lys 128 ), or the topographic region of residues 56-79 (Tyr 56 -Leu 57 -Ile 58 -Tyr 59 -Ser 60 -Gln 61 -Val 62 -Leu 63 -Phe 64 -Lys 65 -Gly 66 -Gln 67 -Gly 68 -Cys 69 -Pro 70 -Ser 71 -Thr 72 -His 73 -Val 74 -Leu 75 -Leu 76 -Thr 77 -His 78 -Thr 79 ), 110-127 (Glu 110 -Ala 111 -Lys 112 -Pro 113 -Trp 114 -Tyr 115 -Glu 116 -Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 -Leu 126 -Glu 127 ) and 135-155 (Glu 135 -Ile 136 -Asn 137 -Arg 138 -Pro 139 -Asp 140 -Tyr 141 -Leu 142 -Asp 143 -Phe 144 -Ala 145 -Glu 146 -Ser 147 -Gly 148 -Gln 149 -Val 150 -Tyr 151 -Phe 152 -Gly 153 -Ile 154 -Ile 155 ), or the topographic region of residues 1-30 (Val 1 -Arg 2 -Ser 3 -Ser 4 -Ser 5 -Arg 6 -Thr 7 -Pro 8 -Ser 9 -Asp 10 -Lys 11 -Pro 12 -Val 13 -Ala 14 -His 15 -Val 16 -Val 17 -Ala 18 -Asn 19 -Pro 20 Gln 21  Ala 22 -Glu 23 -Gly 24 -Gln 25 -Leu 26 -Gln 27 -Trp 28 -Leu 29 -Asn 30 ), 117-128 (Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 -Leu 126 -Glu 127 -Lys 128 ) and 141-153 (Tyr 141 -Leu 142 -Asp 143 -Phe 144 -Ala 145 -Glu 146 -Ser 147 -Gly 148 -Gln 149 -Val 150 -Tyr 15 1-Phe 152 -Gly 153 ), or the topographic region of residues 22-40 (Ala 22 -Glu 23 -Gly 24 -Gln 25 -Leu 26 -Gln 27 -Trp 28 -Leu 29 -Asn 30 -Arg 31 -Arg 32 -Ala 33 -Asn 34 -Ala 35 -Leu 36 -Leu 37 -Ala 38 -Asn 39 -Gly 40 ), 49-97 (Val 49 -Val 50 -Pro 51 -Ser 52 -Glu 53 -Gly 54 -Leu 55 -Tyr 56 -Leu 57 -Ile 58 -Tyr 59 -Ser 60 -Gln 61 -Val 62 -Leu 63 -Phe 64 -Lys 65 -Gly 66 -Gln 67 -Gly 68 -Cys 69 -Pro 70 -Ser 71 -Thr 72 -His 73 -Val 74 -Leu 75 -Leu 76 -Thr 77 -His 78 -Thr 79 -Ile 80 -Ser 81 -Arg 82 -Ile 83 -Ala 84 -Val 85 -Ser 86 -Tyr 87 -Gln 88 -Thr 89 -Lys 90 -Val 91 -Asn 92 -Leu 93 -Leu 94 -Ser 95 -Ala 96 -Ile 97 ), 110-127 (Glu 110 -Ala 111 -Lys 112 -Pro 113 -Trp 114 -Tyr 115 -Glu 116 -Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 -Leu 126 -Glu 127 ) and 136-153 (Ile 136 -Asn 137 -Arg 138 -Pro 139 -Asp 140 -Tyr 141 -Leu 142 -Asp 143 -Phe 144 -Ala 145 -Glu 146 -Ser 147 -Gly 148 -Gln 149 -Val 150 -Tyr 151 -Phe 152 -Gly 153 ), or the topographic region of residues 1-20 (Val 1 -Arg 2 -Ser 3 -Ser 4 -Ser 5 -Arg 6 -Thr 7 -Pro 8 -Ser 9 -Asp 10 -Lys 11 -Pro 12 -Val 13 -Ala 14 -His 15 -Val 16 -Val 17 -Ala 18 -Asn 19 -Pro 20 ) and 76-90 (Leu 76 -Thr 77 -His 78 -Thr 79 -Ile 80 -Ser 81 -Arg 82 -Ile 83 -Ala 84 -Val 85 -Ser 86 -Tyr 87 -Gln 88 -Thr 89 -Lys 90 ), or the topographic region of residues 22-40 (Ala 22 -Glu 23 -Gly 24 -Gln 25 -Leu 26 -Gln 27 -Trp 28 -Leu 29 -Asn 30 -Arg 31 -Arg 32 -Ala 33 -Asn 34 -Ala 35 -Leu 36 -Leu 37 -Ala 38 -Asn 39 -Gly 40 ), 69-97 (Cys 69 -Pro 70 -Ser 71 -Thr 72 -His 73 -Val 74 -Leu 75 -Leu 76 -Thr 77 -His 78 -Thr 79 -Ile 80 -Ser 81 -Arg 82 -Ile 83 -Ala 84 -Val 85 -Ser 86 -Tyr 87 -Gln 88 -Thr 89 -Lys 90 -Val 91 -Asn 92 -Leu 93 -Leu 94 -Ser 95 -Ala 96 -Ile 97 ), 105-128 (Thr 105 -Pro 106 -Glu 107 -Gly 108 -Ala 109 -Glu 110 -Ala 111 -Lys 112 -Pro 113 -Trp 114 -Tyr 115 -Glu 116 -Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 -Leu 126 -Glu 127 -Lys 128 ) and 135-155 (Glu 135 -Ile 136 -Asn 137 -Arg 138 -Pro 139 -Asp 140 -Tyr 141 -Leu 142 -Asp 143 -Phe 144 -Ala 145 -Glu 146 -Ser 147 -Gly 148 -Gln 149 -Val 150 -Tyr 151 -Phe 152 -Gly 153 -Ile 154 -Ile 155 ) is prevented from binding to mature human TNF-α receptor.    
     
     
         34 . An isolated single domain antibody or fragment thereof according to  claim 33 , 
 wherein the antibody binds to TNF-α such that the epitope defined by the topographic regions of 1-18 (Val 1 -Arg 2 -Ser 3 -Ser 4 -Ser 5 -Arg 6 -Thr 7 -Pro 8 -Ser 9 -Asp 10 -Lys 11 -Pro 12 -Val 13 -Ala 14 -His 15 -Val 16 -Val 17 -Ala 18 ), 58-65 (Ile 58 -Tyr 59 -Ser 60 -Gln 61 -Val 62 -Leu 63 -Phe 64 -Lys 65 ), 115-125 (Tyr 115 -Glu 116 -Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 ) and 138-149 (Arg 138 -Pro 139 -Asp 140 -Tyr 141 -Leu 142 -Asp 143 -Phe 144 -Ala 145 -Glu 146 -Ser 147 -Gly 148 -Gln 149 ), or the topographic region of residues 1-18 (Val 1 -Arg 2 -Ser 3 -Ser 4 -Ser 5 -Arg 6 -Thr 7 -Pro 8 -Ser 9 -Asp 10 -Lys 11 -Pro 12 -Val 13 -Ala 14 -His 15 -Val 16 -Val 17 -Ala 18 ) and 108-128 (Gly 108 -Ala 109 -Glu 110 -Ala 111 -Lys 112 -Pro 113 -Trp 114 -Tyr 115 -Glu 116 -Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 -Leu 126 -Glu 127 -Lys 128 ), or the topographic region of residues 56-79 (Tyr 56 -Leu 57 -Ile 58 -Tyr 59 -Ser 60 -Gln 61 -Val 62 -Leu 63 -Phe 64 -Lys 65 -Gly 66 -Gln 67 -Gly 68 -Cys 69 -Pro 70 -Ser 71 -Thr 72 -His 73 -Val 74 -Leu 75 -Leu 76 -Thr 77 -His 78 -Thr 79 ), 110-127 (Glu 110 -Ala 111 -Lys 112 -Pro 113 -Trp 114 -Tyr 115 -Glu 116 -Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 -Leu 126 -Glu 127 ) and 135-155 (Glu 135 -Ile 136 -Asn 137 -Arg 138 -Pro 139 -Asp 140 -Tyr 141 -Leu 142 -Asp 143 -Phe 144 -Ala 145 -Glu 146 -Ser 147 -Gly 148 -Gln 149 -Val 150 -Tyr 151 -Phe 152 -Gly 153 -Ile 154 -Ile 155 ), or the topographic region of residues 1-20 (Val 1 -Arg 2 -Ser 3 -Ser 4 -Ser 5 -Arg 6 -Thr 7 -Pro 8 -Ser 9 -Asp 10 -Lys 11 -Pro 12 -Val 13 -Ala 14 -His 15 -Val 16 -Val 17 -Ala 18 -Asn 19 -Pro 20 ) and 76-90 (Leu 76 -Thr 77 -His 78 -Thr 79 -Ile 80 -Ser 81 -Arg 82 -Ile 83 -Ala 84 -Val 85 -Ser 86 -Tyr 87 -Gln 88 -Thr 89 -Lys 90 ), or the topographic region of residues 22-40 (Ala 22 -Glu 23 -Gly 24 -Gln 25 -Leu 26 -Gln 27 -Trp 28 -Leu 29 -Asn 30 -Arg 31 -Arg 32 -Ala 33 -Asn 34 -Ala 35 -Leu 36 -Leu 37 -Ala 38 -Asn 39 -Gly 40 ), 69-97 (Cys 69 -Pro 70 -Ser 71 -Thr 72 -His 73 -Val 74 -Leu 75 -Leu 76 -Thr 77 -His 78 -Thr 79 -Ile 80 -Ser 81 -Arg 82 -Ile 83 -Ala 84 -Val 85 -Ser 86 -Tyr 87 -Gln 88 -Thr 89 -Lys 90 -Val 91 -Asn 92 -Leu 93 -Leu 94 -Ser 95 -Ala 96 -Ile 97 ), 105-128 (Thr 105 -Pro 106 -Glu 107 -Gly 108 -Ala 109 -Glu 110 -Ala 111 -Lys 112 -Pro 113 -Trp 114 -Tyr 115 -Glu 116 -Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 112 -Gly 122 -Val 123 -Phe 124 -Gln 125 -Leu 126 -Glu 127 -Lys 128 ) and 135-155 (Glu 135 -Ile 136 -Asn 137 -Arg 138 -Pro 139 -Asp 140 -Tyr 141 -Leu 142 -Asp 143 -Phe 144 -Ala 145 -Glu 146 -Ser 147 -Gly 148 -Gln 149 -Val 150 -Tyr 151 -Phe 152 -Gly 153 -Ile 154 -Ile 155 ) is prevented from binding to mature human TNF-α receptor, and    wherein the antibody inhibits cytotoxicity.    
     
     
         35 . An isolated single domain antibody or fragment thereof according to  claim 33   wherein the antibody binds to TNF-α such that the epitope defined by the topographic regions of 1-18 (Val 1 -Arg 2 -Ser 3 -Ser 4 -Ser 5 -Arg 6 -Thr 7 -Pro 8 -Ser 9 -Asp 10 -Lys 11 -Pro 12 -Val 13 -Ala 14 -His 15 -Val 16 -Val 17 -Ala 18 ), 58-65 (Ile 58 -Tyr 59 -Ser 60 -Gln 61 -Val 62 -Leu 63 -Phe 64 -Lys 65 ), 115-125 (Tyr 115 -Glu 116 -Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 ) and 138-149 (Arg 138 -Pro 139 -Asp 140 -Tyr 141 -Leu 142 -Asp 143 -Phe 144 -Ala 145 -Glu 146 -Ser 147 -Gly 148 -Gln 149 ), or the topographic region of residues 1-18 (Val 1 -Arg 2 -Ser 3 -Ser 4 -Ser 5 -Arg 6 -Thr 7 -Pro 8 -Ser 9 -Asp 10 -Lys 11 -Pro 12 -Val 13 -Ala 14 -His 15 -Val 16 -Val 17 -Ala 18 ) and 108-128 (Gly 108 -Ala 109 -Glu 110 -Ala 111 -Lys 112 -Pro 113 -Trp 114 -Tyr 115 -Glu 116 -Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 Leu 126 -Glu 127 -Lys 128 ), or the topographic region of residues 56-79 (Tyr 56 -Leu 57 -Ile 58 -Tyr 59 -Ser 60 -Gln 61 -Val 62 -Leu 63 -Phe 64 -Lys 65 -Gly 66 -Gln 67 -Gly 68 -Cys 69 -Pro 70 -Ser 71 -Thr 72 -His 73 -Val 74 -Leu 75 -Leu 76 -Thr 77 -His 78 -Thr 79 ), 110-127 (Glu 110 -Ala 111 -Lys 112 -Pro 113 -Trp 114 -Tyr 115 -Glu 116 -Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 -Leu 126 -Glu 127 ) and 135-155 (Glu 135 -Ile 136 -Asn 137 -Arg 138 -Pro 139 -Asp 140 -Tyr 141 -Leu 142 -Asp 43 -Phe 144 -Ala 145 -Glu 146 -Ser 147 -Gly 148 -Gln 149 -Val 150 -Tyr 151 -Phe 152 -Gly 153 -Ile 154 -Ile 155 ), or the topographic region of residues 1-20 (Val 1 -Arg 2 -Ser 3 -Ser 4 -Ser 5 -Arg 6 -Thr 7 -Pro 8 -Ser 9 -Asp 10 -Lys 11 -Pro 12 -Val 13 -Ala 14 -His 15 -Val 16 -Val 17 -Ala 18 -Asn 19 -Pro 20 ) and 76-90 (Leu 76 -Thr 77 -His 78 -Thr 79 -Ile 80 -Ser 81 -Arg 82 -Ile 83 -Ala 84 -Val 85 -Ser 86 -Tyr 87 -Gln 88 -Thr 89 -Lys 90 ), or the topographic region of residues 22-40 (Ala 22 -Glu 23 -Gly 24 -Gln 25 -Leu 26 -Gln 27 -Trp 28 -Leu 29 -Asn 30 -Arg 31 -Arg 32 -Ala 33 -Asn 34 -Ala 35 -Leu 36 -Leu 37 -Ala 38 -Asn 39 -Gly 40 ), 69-97 (Cys 69 -Pro 70 -Ser 71 -Thr 72 -His 73 -Val 74 -Leu 75 -Leu 76 -Thr 77 -His 78 -Thr 79 -Ile 80 -Ser 81 -Arg 82 -Ile 83 -Ala 84 -Val 85 -Ser 86 -Tyr 87 -Gln 88 -Thr 89 -Lys 90 -Val 91 -Asn 92 -Leu 93 -Leu 94 -Ser 95 -Ala 96 -Ile 97 ), 105-128 (Thr 105 -Pro 106 -Glu 107 -Gly 108 -Ala 109 -Glu 110 -Ala 111 -Lys 112 -Pro 113 -Trp 114 -Tyr 115 -Glu 116 -Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 -Leu 126 -Glu 127 -Lys 128 ) and 135-155 (Glu 135 -Ile 136 -Asn 137 -Arg 138 -Pro 139 -Asp 140 -Tyr 141 -Leu 142 -Asp 143 -Phe 144 -Ala 145 -Glu 146 -Ser 147 -Gly 148 -Gln 149 -Val 150 -Tyr 151 -Phe 152 -Gly 153 -Ile 154 -Ile 155 ) is prevented from binding to mature human TNF-α receptor, and    wherein the antibody inhibits tumor regression.    
     
     
         36 . An isolated single domain antibody or fragment thereof according to  claim 33   wherein the antibody binds to TNF-α such that the epitope defined by the topographic regions of wherein the antibody binds to TNF-α such that the epitope defined by the topographic region of residues 1-30 (Val 1 -Arg 2 -Ser 3 -Ser 4 -Ser 5 -Arg 6 -Thr 7 -Pro 8 -Ser 9 -Asp 10 -Lys 11 -Pro 12 -Val 13 -Ala 14 -His 15 -Val 16 -Val 17 -Ala 18 -Asn 19 -Pro 20 Gln 2  Ala 22 -Glu 23 -Gly 24 -Gln 25 -Leu 26 -Gln 27 -Trp 28 -Leu 29 -Asn 30 ), 117-128 (Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 Leu 126 -Glu 127 -Lys 128 ) and 141-153 (Tyr 141 -Leu 142 -Asp 143 -Phe 144 -Ala 145 -Glu 146 -Ser 147 -Gly 148 -Gln 149 -Val 150 -Tyr 151 -Phe 152 -Gly 153 ) or the topographic region of residues 22-40 (Ala 22 -Glu 23 -Gly 24 -Gln 25 -Leu 26 -Gln 27 -Trp 28 -Leu 29 -Asn 30 -Arg 31 -Arg 32 -Ala 33 -Asn 34 -Ala 35 -Leu 36 -Leu 37 -Ala 38 -Asn 39 -Gly 40 ), 49-97 (Val 49 -Val 50 -Pro 51 -Ser 52 -Glu 53 -Gly 54 -Leu 55 -Tyr 56 -Leu 57 -Ile 58 -Tyr 59 -Ser 60 -Gln 61 -Val 62 -Leu 63 -Phe 64 -Lys 65 -Gly 66 -Gln 67 -Gly 68 -Cys 69 -Pro 70 -Ser 71 -Thr 72 -His 73 -Val 74 -Leu 75 -Leu 76 -Thr 77 -His 78 -Thr 79 -Ile 80 -Ser 81 -Arg 82 -Ile 83 -Ala 84 -Val 85 -Ser 86 -Tyr 87 -Gln 88 -Thr 89 -Lys 90 -Val 91 -Asn 92 -Leu 93 -Leu 94 -Ser 95 -Ala 96 -Ile 97 ), 110-127 (Glu 110 -Ala 111 -Lys 112 -Pro 113 -Trp 114 -Tyr 115 -Glu 116 -Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 -Leu 126 -Glu 127 ) and 136-153 (Ile 136 -Asn 137 -Arg 138 -Pro 139 -Asp 140 -Tyr 141 -Leu 142 -Asp 143 -Phe 144 -Ala 145 -Glu 146 -Ser 147 -Gly 148 -Gln 149 -Val 150 -Tyr 151 -Phe 152 -Gly 153 ) is prevented from binding to mature human TNF-α receptor and    wherein the antibody has no effect on cytotoxicity.    
     
     
         37 . An isolated single domain antibody or fragment thereof according to any one of claims  33 - 36 , wherein the antibody is a humanized antibody.  
     
     
         38 . An isolated single domain antibody or fragment thereof according to any one of claims  33 - 36 , wherein the antibody is a chimeric antibody.  
     
     
         39 . An isolated single domain antibody or fragment thereof according to any one of claims  33 - 36 , wherein the antibody is a human antibody.  
     
     
         40 . A composition comprising an isolated single domain antibody or fragment thereof that binds to mature human TNF-α, 
 wherein the antibody is characterized in that when the antibody binds to TNF-α the induction of endothelial procoagulant activity is inhibited,    wherein the antibody binds to TNF-α such that the epitope defined by the topographic regions of 1-18 (Val 1 -Arg 2 -Ser 3 -Ser 4 -Ser 5 -Arg 6 -Thr 7 -Pro 8 -Ser 9 -Asp 10 -Lys 11 -Pro 12 -Val 13 -Ala 14 -His 15 -Val 16 -Val 17 -Ala 18 ), 58-65 (Ile 58 -Tyr 59 -Ser 60 -Gln 61 -Val 62 -Leu 63 -Phe 64 -Lys 65 ), 115-125 (Tyr 115 -Glu 116 -Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 ) and 138-149 (Arg 138 -Pro 139 -Asp 140 -Tyr 141 -Leu 142 -Asp 143 -Phe 144 -Ala 145 -Glu 146 -Ser 147 -Gly 148 -Gln 149 ), or the topographic region of residues 1-18 (Val 1 -Arg 2 -Ser 3 -Ser 4 -Ser 5 -Arg 6 -Thr 7 -Pro 8 -Ser 9 -Asp 10 -Lys 11 -Pro 12 -Val 13 -Ala 14 -His 15 -Val 16 -Val 17 -Ala 18 ) and 108-128 (Gly 108 -Ala 109 -Glu 110 -Ala 111 -Lys 112 -Pro 113 -Trp 114 -Tyr 115 -Glu 116 -Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 -Leu 126 -Glu 127 -Lys 128 ), or the topographic region of residues 56-79 (Tyr 56 -Leu 57 -Ile 58 -Tyr 59 -Ser 60 -Gln 61 -Val 62 -Leu 63 -Phe 64 -Lys 65 -Gly 66 -Gln 67 -Gly 68 -Cys 69 -Pro 70 -Ser 71 -Thr 72 -His 73 -Val 74 -Leu 75 -Leu 76 -Thr 77 -His 78 -Thr 79 ), 110-127 (Glu 110 -Ala 111 -Lys 112 -Pro 113 -Trp 114 -Tyr 115 -Glu 116 -Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 -Leu 126 -Glu 127 ) and 135-155 (Glu 135 -Ile 136 -Asn 137 -Arg 138 -Pro 139 -Asp 140 -Tyr 141 -Leu 142 -Asp 143 -Phe 144 -Ala 145 -Glu 146 -Ser 147 -Gly 148 -Gln 149 -Val 150 -Tyr 151 -Phe 152 -Gly 153 -Ile 154 -Ile 155 ), or the topographic region of residues 1-30 (Val 1 -Arg 2 -Ser 3 -Ser 4 -Ser 5 -Arg 6 -Thr 7 -Pro 8 -Ser 9 -Asp 10 -Lys 11 -Pro 12 -Val 13 -Ala 14 -His 15 -Val 16 -Val 17 -Ala 18 -Asn 19 -Pro 20 Gln 21  Ala 22 -Glu 23 -Gly 24 -Gln 25 -Leu 26 -Gln 27 -Trp 28 -Leu 29 -Asn 30 ), 117-128 (Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 -Leu 126 -Glu 127 -Lys 128 ) and 141-153 (Tyr 141 -Leu 142 -Asp 143 -Phe 144 -Ala 145 -Glu 146 -Ser 147 -Gly 148 -Gln 149 -Val 150 -Tyr 151 -Phe 152 -Gly 153 ), or the topographic region of residues 22-40 (Ala 22 -Glu 23 -Gly 24 -Gln 25 -Leu 26 -Gln 27 -Trp 28 -Leu 29 -Asn 30 -Arg 31 -Arg 32 -Ala 33 -Asn 34 -Ala 35 -Leu 36 -Leu 37 -Ala 38 -Asn 39 -Gly 40 ), 49-97 (Val 49 -Val 50 -Pro 51 -Ser 52 -Glu 53 -Gly 54 -Leu 55 -Tyr 56 -Leu 57 -Ile 58 -Tyr 59 -Ser 60 -Gln 61 -Val 62 -Leu 63 -Phe 64 -Lys 65 -Gly 66 -Gln 67 -Gly 68 -Cys 69 -Pro 70 -Ser 71 -Thr 72 -His 73 -Val 74 -Leu 75 -Leu 76 -Thr 77 -His 78 -Thr 79 -Ile 80 -Ser 81 -Arg 82 -Ile 83 -Ala 84 -Val 85 -Ser 86 -Tyr 87 -Gln 88 -Thr 89 -Lys 90 -Val 91 -Asn 92 -Leu 93 -Leu 94 -Ser 95 -Ala 96 -Ile 97 ), 110-127 (Glu 110 -Ala 111 -Lys 112 -Pro 113 -Trp 114 -Tyr 115 -Glu 116 -Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 -Leu 126 -Glu 127 ) and 136-153 (Ile 136 -Asn 137 -Arg 138 -Pro 139 -Asp 140 -Tyr 141 -Leu 142 -Asp 143 -Phe 144 -Ala 145 -Glu 146 -Ser 147 -Gly 148 -Gln 149 -Val 150 -Tyr 151 -Phe 152 -Gly 153 ), or the topographic region of residues 1-20 (Val 1 -Arg 2 -Ser 3 -Ser 4 -Ser 5 -Arg 6 -Thr 7 -Pro 8 -Ser 9 -Asp 10 -Lys 11 -Pro 12 -Val 13 -Ala 14 -His 15 -Val 16 -Val 17 -Ala 18 -Asn 19 -Pro 20 ) and 76-90 (Leu 76 -Thr 77 -His 78 -Thr 79 -Ile 80 -Ser 81 -Arg 82 -Ile 83 -Ala 84 -Val 85 -Ser 86 -Tyr 87 -Gln 88 -Thr 89 -Lys 90 ), or the topographic region of residues 22-40 (Ala 22 -Glu 23 -Gly 24 -Gln 25 -Leu 26 -Gln 27 -Trp 28 -Leu 29 -Asn 30 -Arg 31 -Arg 32 -Ala 33 -Asn 34 -Ala 35 -Leu 36 -Leu 37 -Ala 38 -Asn 39 -Gly 40 ), 69-97 (Cys 69 -Pro 70 -Ser 71 -Thr 72 -His 73 -Val 74 -Leu 75 -Leu 76 -Thr 77 -His 78 -Thr 79 -Ile 80 -Ser 81 -Arg 82 -Ile 83 -Ala 84 -Val 85 -Ser 86 -Tyr 87 -Gln 88 -Thr 89 -Lys 90 -Val 91 -Asn 92 -Leu 93 -Leu 94 -Ser 95 -Ala 96 -Ile 97 ), 105-128 (Thr 105 -Pro 106 -Glu 107 -Gly 108 -Ala 109 -Glu 110 -Ala 111 -Lys 112 -Pro 113 -Trp 114 -Tyr 115 -Glu 116 -Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 -Leu 126 -Glu 127 -Lys 128 ) and 135-155 (Glu 135 -Ile 136 -Asn 137 -Arg 138 -Pro 139 -Asp 140 -Tyr 141 -Leu 142 -Asp 143 -Phe 144 -Ala 145 -Glu 146 -Ser 147 -Gly 148 -Gln 149 -Val 150 -Tyr 151 -Phe 152 -Gly 153 -Ile 154 -Ile 155 ) is prevented from binding to mature human TNF-α receptor.    
     
     
         41 . A composition according to  claim 40 , 
 wherein the antibody binds to TNF-α such that the epitope defined by the topographic regions of 1-18 (Val 1 -Arg 2 -Ser 3 -Ser 4 -Ser 5 -Arg 6 -Thr 7 -Pro 8 -Ser 9 -Asp 10 -Lys 11 -Pro 12 -Val 13 -Ala 14 -His 15 -Val 16 -Val 17 -Ala 18 ), 58-65 (Ile 58 -Tyr 59 -Ser 60 -Gln 61 -Val 62 -Leu 63 -Phe 64 -Lys 65 ), 115-125 (Tyr 115 -Glu 116 -Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 ) and 138-149 (Arg 138 -Pro 139 -Asp 140 -Tyr 141 -Leu 142 -Asp 143 -Phe 144 -Ala 145 -Glu 146 -Ser 147 -Gly 148 -Gln 149 ), or the topographic region of residues 1-18 (Val 1 -Arg 2 -Ser 3 -Ser 4 -Ser 5 -Arg 6 -Thr 7 -Pro 8 -Ser 9 -Asp 10 -Lys 11 -Pro 12 -Val 13 -Ala 14 -His 15 -Val 16 -Val 17 -Ala 18 ) and 108-128 (Gly 108 -Ala 109 -Glu 110 -Ala 111 -Lys 112 -Pro 113 -Trp 114 -Tyr 115 -Glu 116 -Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 -Leu 126 -Glu 127 -Lys 128 ), or the topographic region of residues 56-79 (Tyr 56 -Leu 57 -Ile 58 -Tyr 59 -Ser 60 -Gln 61 -Val 62 -Leu 63 -Phe 64 -Lys 65 -Gly 66 -Gln 67 -Gly 68 -Cys 69 -Pro 70 -Ser 71 -Thr 72 -His 73 -Val 74 -Leu 75 -Leu 76 -Thr 77 -His 78 -Thr 79 ), 110-127 (Glu 110 -Ala 111 -Lys 112 -Pro 113 -Trp 114 -Tyr 115 -Glu 116 -Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 -Leu 126 -Glu 127 ) and 135-155 (Glu 135 -Ile 136 -Asn 137 -Arg 138 -Pro 139 -Asp 140 -Tyr 141 -Leu 142 -Asp 143 -Phe 144 -Ala 145 -Glu 146 -Ser 147 -Gly 148 -Gln 149 -Val 150 -Tyr 151 -Phe 152 -Gly 153 -Ile 154 -Ile 155 ), or the topographic region of residues 1-20 (Val 1 -Arg 2 -Ser 3 -Ser 4 -Ser 5 -Arg 6 -Thr 7 -Pro 8 -Ser 9 -Asp 10 -Lys 11 -Pro 12 -Val 13 -Ala 14 -His 15 -Val 16 -Val 17 -Ala 18 -Asn 19 -Pro 20 ) and 76-90 (Leu 76 -Thr 77 -His 78 -Thr 79 -Ile 80 -Ser 81 -Arg 82 -Ile 83 -Ala 84 -Val 85 -Ser 86 -Tyr 87 -Gln 88 -Thr 89 -Lys 90 ), or the topographic region of residues 22-40 (Ala 22 -Glu 23 -Gly 24 -Gln 25 -Leu 26 -Gln 27 -Trp 28 -Leu 29 -Asn 30 -Arg 31 -Arg 32 -Ala 33 -Asn 34 -Ala 35 -Leu 36 -Leu 37 -Ala 38 -Asn 39 -Gly 40 ), 69-97 (Cys 69 -Pro 70 -Ser 71 -Thr 72 -His 73 -Val 74 -Leu 75 -Leu 76 -Thr 77 -His 78 -Thr 79 -Ile 80 -Ser 81 -Arg 82 -Ile 83 -Ala 84 -Val 85 -Ser 86 -Tyr 87 -Gln 88 -Thr 89 -Lys 90 -Val 91 -Asn 92 -Leu 93 -Leu 94 -Ser 95 -Ala 96 -Ile 97 ), 105-128 (Thr 105 -Pro 106 -Glu 107 -Gly 108 -Ala 109 -Glu 110 -Ala 111 -Lys 112 -Pro 113 -Trp 114 -Tyr 115 -Glu 116 -Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 -Leu 126 -Glu 127 -Lys 128 ) and 135-155 (Glu 135 -Ile 136 -Asn 137 -Arg 138 -Pro 139 -Asp 140 -Tyr 141 -Leu 142 -Asp 143 -Phe 144 -Ala 145 -Glu 146 -Ser 147 -Gly 148 -Gln 149 -Val 150 -Tyr 151 -Phe 152 -Gly 153 -Ile 154 -Ile 55 ) is prevented from binding to mature human TNF-α receptor, and    wherein the antibody inhibits cytotoxicity.    
     
     
         42 . A composition according to  claim 40 , 
 wherein the antibody binds to TNF-α such that the epitope defined by the topographic regions of 1-18 (Val 1 -Arg 2 -Ser 3 -Ser 4 -Ser 5 -Arg 6 -Thr 7 -Pro 8 -Ser 9 -Asp 10 -Lys 11 -Pro 12 -Val 13 -Ala 14 -His 15 -Val 16 -Val 17 -Ala 18 ), 58-65 (Ile 58 -Tyr 59 -Ser 60 -Gln 61 -Val 62 -Leu 63 -Phe 64 -Lys 65 ), 115-125 (Tyr 115 -Glu 116 -Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 ) and 138-149 (Arg 138 -Pro 139 -Asp 140 -Tyr 141 -Leu 142 -Asp 143 -Phe 144 -Ala 145 -Glu 146 -Ser 147 -Gly 148 -Gln 149 ), or the topographic region of residues 1-18 (Val 1 -Arg 2 -Ser 3 -Ser 4 -Ser 5 -Arg 6 -Thr 7 -Pro 8 -Ser 9 -Asp 10 -Lys 11 -Pro 12 -Val 13 -Ala 14 -His 15 -Val 16 -Val 17 -Ala 18 ) and 108-128 (Gly 108 -Ala 109 -Glu 110 -Ala 111 -Lys 112 -Pro 113 -Trp 114 -Tyr 115 -Glu 116 -Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 -Leu 126 -Glu 127 -Lys 128 ), or the topographic region of residues 56-79 (Tyr 56 -Leu 57 -Ile 58 -Tyr 59 -Ser 60 -Gln 61 -Val 62 -Leu 63 -Phe 64 -Lys 65 -Gly 66 -Gln 67 -Gly 68 -Cys 69 -Pro 70 -Ser 71 -Thr 72 -His 73 -Val 74 -Leu 75 -Leu 76 -Thr 77 -His 78 -Thr 79 ), 110-127 (Glu 110 -Ala 111 -Lys 112 -Pro 113 -Trp 114 -Tyr 115 -Glu 116 -Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 -Leu 126 -Glu 127 ) and 135-155 (Glu 135 -Ile 136 -Asn 137 -Arg 138 -Pro 139 -Asp 140 -Tyr 141 -Leu 142 -Asp 143 -Phe 144 -Ala 145 -Glu 146 -Ser 147 -Gly 148 -Gln 149 -Val 150 -Tyr 151 -Phe 152 -Gly 153 -Ile 154 -Ile 155 ), or the topographic region of residues 1-20 (Val 1 -Arg 2 -Ser 3 -Ser 4 -Ser 5 -Arg 6 -Thr 7 -Pro 8 -Ser 9 -Asp 10 -Lys 11 -Pro 12 -Val 13 -Ala 14 -His 15 -Val 16 -Val 17 -Ala 18 -Asn 19 -Pro 20 ) and 76-90 (Leu 76 -Thr 77 -His 78 -Thr 79 -Ile 80 -Ser 81 -Arg 82 -Ile 83 -Ala 84 -Val 85 -Ser 86 -Tyr 87 -Gln 88 -Thr 89 -Lys 90 ), or the topographic region of residues 22-40 (Ala 22 -Glu 23 -Gly 24 -Gln 25 -Leu 26 -Gln 27 -Trp 28 -Leu 29 -Asn 30 -Arg 31 -Arg 32 -Ala 33 -Asn 34 -Ala 35 -Leu 36 -Leu 37 -Ala 38 -Asn 39 -Gly 40 ), 69-97 (Cys 69 -Pro 70 -Ser 71 -Thr 72 -His 73 -Val 74 -Leu 75 -Leu 76 -Thr 77 -His 78 -Thr 79 -Ile 80 -Ser 81 -Arg 82 -Ile 83 -Ala 84 -Val 85 -Ser 86 -Tyr 87 -Gln 88 -Thr 89 -Lys 90 -Val 91 -Asn 92 -Leu 93 -Leu 94 -Ser 95 -Ala 96 -Ile 97 ), 105-128 (Thr 105 -Pro 106 -Glu 107 -Gly 108 -Ala 109 -Glu 110 -Ala 111 -Lys 112 -Pro 113 -Trp 114 -Tyr 115 -Glu 116 -Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 -Leu 126 -Glu 127 -Lys 128 ) and 135-155 (Glu 135 -Ile 136 -Asn 137 -Arg 138 -Pro 139 -Asp 140 -Tyr 141 -Leu 142 -Asp 143 -Phe 144 -Ala 145 -Glu 146 -Ser 147 -Gly 148 -Gln 149 -Val 150 -Tyr 151 -Phe 152 -Gly 153 -Ile 154 -Ile 155 ), and    wherein the antibody inhibits tumor regression.    
     
     
         43 . A composition according to  claim 40 , 
 wherein the antibody binds to TNF-α such that the epitope defined by the topographic regions of wherein the antibody binds to TNF-α such that the epitope defined by the topographic region of residues 1-30 (Val 1 -Arg 2 -Ser 3 -Ser 4 -Ser 5 -Arg 6 -Thr 7 -Pro 8 -Ser 9 -Asp 10 -Lys 11 -Pro 12 -Val 13 -Ala 14 -His 15 -Val 16 -Val 17 -Ala 18 -Asn 19 -Pro 20 Gln 21 Ala 22 -Glu 23 -Gly 24 -Gln 25 -Leu 26 -Gln 27 -Trp 28 -Leu 29 -Asn 30 ), 117-128 (Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 -Leu 126 -Glu 127 -Lys 128 ) and 141-153 (Tyr 141 -Leu 142 -Asp 143 -Phe 144 -Ala 145 -Glu 146 -Ser 147 -Gly 148 -Gln 149 -Val 150 -Tyr 151 -Phe 152 -Gly 153 ), or the topographic region of residues 22-40 (Ala 22 -Glu 23 -Gly 24 -Gln 25 -Leu 26 -Gln 27 -Trp 28 -Leu 29 -Asn 30 -Arg 31 -Arg 32 -Ala 33 -Asn 34 -Ala 35 -Leu 36 -Leu 37 -Ala 38 -Asn 39 -Gly 40 ), 49-97 (Val 49 -Val 50 -Pro 51 -Ser 52 -Glu 53 -Gly 54 -Leu 55 -Tyr 56 -Leu 57 -Ile 58 -Tyr 59 -Ser 60 -Gln 61 -Val 62 -Leu 63 -Phe 64 -Lys 65 -Gly 66 -Gln 67 -Gly 68 -Cys 69 -Pro 70 -Ser 71 -Thr 72 -His 73 -Val 74 -Leu 75 -Leu 76 -Thr 77 -His 78 -Thr 79 -Ile 80 -Ser 81 -Arg 82 -Ile 83 -Ala 84 -Val 85 -Ser 86 -Tyr 87 -Gln 88 -Thr 89 -Lys 90 -Val 91 -Asn 92 -Leu 93 -Leu 94 -Ser 95 -Ala 96 -Ile 97 ), 110-127 (Glu 110 -Ala 111 -Lys 112 -Pro 113 -Trp 114 -Tyr 115 -Glu 116 -Pro 117 -Ile 118 -Tyr 119 -Leu 120 -Gly 121 -Gly 122 -Val 123 -Phe 124 -Gln 125 -Leu 126 -Glu 127 ) and 136-153 (Ile 136 -Asn 137 -Arg 138 -Pro 139 -Asp 140 -Tyr 141 -Leu 142 -Asp 143 -Phe 144 -Ala 145 -Glu 146 -Ser 147 -Gly 148 -Gln 149 -Val 150 -Tyr 151 -Phe 152 -Gly 153 ) is prevented from binding to mature human TNF-α receptor and wherein the antibody has no effect on cytotoxicity.    
     
     
         44 . A composition according to any of claims  40 - 43 , wherein the antibody is a humanized antibody.  
     
     
         45 . A composition according to any of claims  40 - 43 , wherein the antibody is a chimeric antibody.  
     
     
         46 . A composition according to any of claims  40 - 43 , wherein the antibody is a human antibody.

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