US2004214993A2PendingUtilityA2
Tumour necrosis factor binding ligands
Est. expiryFeb 18, 2012(expired)· nominal 20-yr term from priority
C07K 2317/75C07K 2319/00C07K 2317/73C07K 2317/622C07K 2317/56C07K 2317/92A61K 38/00A61K 47/6813C07K 2317/24C07K 16/241A61K 47/68A61K 2039/505C07K 2317/21
67
PatentIndex Score
0
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0
Claims
Abstract
Abstract of the Disclosure 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-modifiedWhat is Claimed is:
1. Claim 1 (cancelled)
2. Claim 2 (cancelled)
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58. Claim 58 (cancelled)
59. Claim 59 .An isolated antibody or fragment thereof that specifically binds to mature human TNF-α,
wherein the antibody or fragment thereof competitively inhibits MAb 53 (accession No. 90012433) for specific binding to mature human TNF-α and,
wherein when the antibody or fragment thereof binds mature human TNF-α, the induction of tumor fibrin deposition is unaffected, and the induction of endothelial procoagulant activity, cytotoxicity, tumor regression and tumor receptor binding are inhibited.
60. Claim 60 .An antibody or fragment thereof according to claim 59 ,
wherein the antibody or fragment thereof competitively inhibits the binding of MAb 53 (accession No. 90012433) to mature human TNF-α, where comparative binding specificity is determined by antibody-antibody competition assays in the presence of mature human TNF-α.
61. Claim 61 .An antibody or fragment thereof according to claim 59 wherein the antibody is a monoclonal antibody.
62. Claim 62 .An antibody or fragment thereof according to any one of claims 59-61, wherein the antibody is a humanized antibody.
63. Claim 63 .An antibody or fragment thereof according to any one of claims 59-61, wherein the antibody is a chimeric antibody.
64. Claim 64 .A composition comprising an isolated antibody or fragment thereof that specifically binds to mature human TNF-α,
wherein the antibody or fragment thereof competitively inhibits MAb 53 (accession No. 90012433) for specific binding to mature human TNF-α and,
wherein when the antibody or fragment thereof binds mature human TNF-α, the induction of tumor fibrin deposition is unaffected, and the induction of endothelial procoagulant activity, cytotoxicity, tumor regression and tumor receptor binding are inhibited.
65. Claim 65 .A composition according to claim 64 , wherein the antibody or fragment thereof competitively inhibits the binding of MAb 53 (accession No. 90012433) to mature human TNF-α, where comparative binding specificity is determined by antibody-antibody competition assays in the presence of mature human TNF-α.
66. Claim 66 .A composition according to claim 64 wherein the antibody is a monoclonal antibody.
67. Claim 67 .A composition according to any one of claims 64-66, wherein the antibody is a humanized antibody.
68. Claim 68 .A composition according to any one of claims 64-66, wherein the antibody is a chimeric antibody.
69. Claim 69 .An isolated single chain antibody that specifically binds to mature human TNF-α,
wherein the antibody competitively inhibits MAb 53 (accession No. 90012433) for specific binding to mature human TNF-α and,
wherein when the antibody binds mature human TNF-α, the induction of tumor fibrin deposition is unaffected, and the induction of endothelial procoagulant activity, cytotoxicity, tumor regression and tumor receptor binding are inhibited.
70. Claim 70 .An antibody according to claim 69 , wherein the antibody competitively inhibits the binding of MAb 53 (accession No. 90012433) to mature human TNF-α, where comparative binding specificity is determined by antibody-antibody competition assays in the presence of mature human TNF-α.
71. Claim 71 .An antibody according to claim 69 or 70 , wherein the antibody is a humanized antibody.
72. Claim 72 .An antibody according to claim 69 or 70 , wherein the antibody is a chimeric antibody.
73. Claim 73 .A composition comprising an isolated single chain antibody that specifically binds to mature human TNF-α,
wherein the antibody competitively inhibits MAb 53 (accession No. 90012433) for specific binding to mature human TNF-α and,
wherein when the antibody binds mature human TNF-α, the induction of tumor fibrin deposition is unaffected, and the induction of endothelial procoagulant activity, cytotoxicity, tumor regression and tumor receptor binding are inhibited.
74. Claim 74 .A composition according to claim 73 , wherein the antibody competitively inhibits the binding of MAb 53 (accession No. 90012433) to mature human TNF-α, where comparative binding specificity is determined by antibody-antibody competition assays in the presence of mature human TNF-α.
75. Claim 75 .A composition according to claim 73 or 74 , wherein the antibody is a humanized antibody.
76. Claim 76 .A composition according to claim 73 or 74 , wherein the antibody is a chimeric antibody.
77. Claim 77 (cancelled)
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219. Claim 219 (cancelled)
220. Claim 220 (cancelled)
221. Claim 221 .An isolated antibody or fragment thereof that specifically binds to mature human TNF-α,
wherein when the antibody or fragment thereof binds mature human TNF-α, the induction of endothelial procoagulant activity is inhibited,
wherein the isolated antibody or fragment thereof competitively inhibits a second antibody or fragment thereof for specific binding to mature human TNF-α; and,
wherein the second antibody or fragment thereof binds to peptides having amino acid sequences 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
, 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
, 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 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
of the mature human TNF-α amino acid sequence.
222. Claim 222 .An antibody or fragment thereof according to claim 221 , wherein the antibody is a monoclonal antibody.
223. Claim 223 .An antibody or fragment thereof according to claim 221 , wherein the antibody or fragment thereof has no effect on the induction of tumor fibrin deposition activity.
224. Claim 224 .An antibody or fragment thereof according to claim 221 , wherein the antibody or fragment thereof inhibits tumor receptor binding.
225. Claim 225 .An antibody or fragment thereof according to claim 224 , wherein the antibody or fragment thereof inhibits cytotoxicity.
226. Claim 226 .An antibody or fragment thereof according to claim 221 , wherein the antibody or fragment thereof inhibits cytotoxicity.
227. Claim 227 .An antibody or fragment thereof according to claim 226 , wherein the antibody or fragment thereof inhibits tumor regression.
228. Claim 228 .An antibody or fragment thereof according to claim 225 , wherein the antibody or fragment thereof inhibits tumor regression.
229. Claim 229 .An antibody or fragment thereof according to claim 224 , wherein the antibody or fragment thereof inhibits tumor regression.
230. Claim 230 .An antibody or fragment thereof according to claim 221 , wherein the antibody or fragment thereof inhibits tumor regression.
231. Claim 231 .The antibody or fragment thereof according to claim 221 , wherein when the antibody or fragment thereof binds mature human TNF-α, the induction of tumor fibrin deposition is unaffected, and cytotoxicity, tumor regression and tumor receptor binding activities are inhibited.
232. Claim 232 .An antibody or fragment thereof according to claim 221 , where comparative binding specificity between the antibody or fragment thereof and the second antibody or fragment thereof is determined by antibody-antibody competition assays in the presence of mature human TNF-α.
233. Claim 233 .An antibody or fragment thereof according to claim 232 , wherein the antibody or fragment thereof inhibits tumor receptor binding.
234. Claim 234 .An antibody or fragment thereof according to claim 233 , wherein the antibody or fragment thereof inhibits cytotoxicity.
235. Claim 235 .An antibody or fragment thereof according to claim 232 , wherein the antibody or fragment thereof inhibits cytotoxicity.
236. Claim 236 .An antibody or fragment thereof according to claim 234 , wherein the antibody or fragment thereof inhibits tumor regression.
237. Claim 237 .An antibody or fragment thereof according to claim 232 , wherein the antibody or fragment thereof inhibits tumor regression.
238. Claim 238 .An antibody or fragment thereof according to claim 232 , wherein the antibody or fragment thereof competitively inhibits the binding of the second antibody or fragment thereof to mature human TNF-α, where comparative binding specificity is determined by antibody-antibody competition assays in the presence of mature human TNF-α; and,
wherein when the antibody or fragment thereof binds mature human TNF-α, the induction of tumor fibrin deposition is unaffected, and cytotoxicity, tumor regression and tumor receptor binding activities are inhibited.
239. Claim 239 .An antibody or fragment thereof according to any one of claims 221-238, wherein the antibody is a humanized antibody.
240. Claim 240 .An antibody or fragment thereof according to any one of claims 221-238, wherein the antibody is a chimeric antibody.
241. Claim 241 .A composition comprising an isolated antibody or fragment thereof that specifically binds to mature human TNF-α,
wherein when the antibody or fragment thereof binds mature human TNF-α, the induction of endothelial procoagulant activity is inhibited,
wherein the isolated antibody or fragment thereof competitively inhibits a second antibody or fragment thereof for specific binding to mature human TNF-α; and,
wherein the second antibody or fragment thereof binds to peptides having amino acid sequences 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
, 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
, 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 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
of the mature human TNF-α amino acid sequence.
242. Claim 242 .A composition according to claim 241 , wherein the antibody is a monoclonal antibody.
243. Claim 243 .A composition according to claim 241 , wherein the antibody or fragment thereof has no effect on the induction of tumor fibrin deposition activity.
244. Claim 244 .A composition according to claim 241 , wherein the antibody or fragment thereof inhibits tumor receptor binding.
245. Claim 245 .A composition according to claim 244 , wherein the antibody or fragment thereof inhibits cytotoxicity.
246. Claim 246 .A composition according to claim 241 , wherein the antibody or fragment thereof inhibits cytotoxicity.
247. Claim 247 .A composition according to claim 246 , wherein the antibody or fragment thereof inhibits tumor regression.
248. Claim 248 .A composition according to claim 245 , wherein the antibody or fragment thereof inhibits tumor regression.
249. Claim 249 .A composition according to claim 244 , wherein the antibody or fragment thereof inhibits tumor regression.
250. Claim 250 .A composition according to claim 241 , wherein the antibody or fragment thereof inhibits tumor regression.
251. Claim 251 .A composition according to claim 241 , wherein when the antibody or fragment thereof binds mature human TNF-α, the induction of tumor fibrin deposition is unaffected, and cytotoxicity, tumor regression and tumor receptor binding activities are inhibited.
252. Claim 252 .A composition according to claim 241 , where comparative binding specificity between the antibody or fragment thereof and the second antibody or fragment thereof is determined by antibody-antibody competition assays in the presence of mature human TNF-α.
253. Claim 253 .A composition according to claim 252 , wherein the antibody or fragment thereof inhibits tumor receptor binding.
254. Claim 254 .A composition according to claim 253 , wherein the antibody or fragment thereof inhibits cytotoxicity.
255. Claim 255 .A composition according to claim 252 , wherein the antibody or fragment thereof inhibits cytotoxicity.
256. Claim 256 .A composition according to claim 254 , wherein the antibody or fragment thereof inhibits tumor regression.
257. Claim 257 .A composition according to claim 252 , wherein the antibody or fragment thereof inhibits tumor regression.
258. Claim 258 .A composition according to claim 241 , wherein the antibody or fragment thereof competitively inhibits the binding of the second antibody or fragment thereof to mature human TNF-α, where comparative binding specificity is determined by antibody-antibody competition assays in the presence of mature human TNF-α; and,
wherein when the antibody or fragment thereof binds mature human TNF-α, the induction of tumor fibrin deposition is unaffected, and cytotoxicity, tumor regression and tumor receptor binding activities are inhibited.
259. Claim 259 .A composition according to any one of claims 241-258, wherein the antibody is a humanized antibody.
260. Claim 260 .A composition according to any one of claims 241-258, wherein the antibody is a chimeric antibody.
261. Claim 261 .An isolated single chain antibody that specifically binds to mature human TNF-α,
wherein when the antibody binds mature human TNF-α, the induction of endothelial procoagulant activity is inhibited,
wherein the isolated antibody competitively inhibits a second antibody or fragment thereof for specific binding to mature human TNF-α; and
wherein the second antibody or fragment thereof binds to peptides having amino acid sequences 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
, 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
, 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 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
of the mature human TNF-α amino acid sequence.
262. Claim 262 .An antibody according to claim 261 , wherein the antibody has no effect on the induction of tumor fibrin deposition activity.
263. Claim 263 .An antibody according to claim 261 , wherein the antibody inhibits tumor receptor binding.
264. Claim 264 .An antibody according to claim 263 , wherein the antibody inhibits cytotoxicity.
265. Claim 265 .An antibody according to claim 261 , wherein the antibody inhibits cytotoxicity.
266. Claim 266 .An antibody according to claim 265 , wherein the antibody inhibits tumor regression.
267. Claim 267 .An antibody according to claim 264 , wherein the antibody inhibits tumor regression.
268. Claim 268 .An antibody according to claim 263 , wherein the antibody inhibits tumor regression.
269. Claim 269 .An antibody according to claim 261 , wherein the antibody inhibits tumor regression.
270. Claim 270 .An antibody according to claim 261 , wherein when the antibody binds mature human TNF-α, the induction of tumor fibrin deposition is unaffected, and cytotoxicity, tumor regression and tumor receptor binding activities are inhibited.
271. Claim 271 .An antibody according to claim 261 , where comparative binding specificity between the antibody and the second antibody is determined by antibody-antibody competition assays in the presence of mature human TNF-α.
272. Claim 272 .An antibody according to claim 271 , wherein the antibody inhibits tumor receptor binding.
273. Claim 273 .An antibody according to claim 272 , wherein the antibody inhibits cytotoxicity.
274. Claim 274 .An antibody according to claim 271 , wherein the antibody inhibits cytotoxicity.
275. Claim 275 .An antibody according to claim 273 , wherein the antibody inhibits tumor regression.
276. Claim 276 .An antibody according to claim 271 , wherein the antibody inhibits tumor regression.
277. Claim 277 .An antibody according to claim 261 , wherein the antibody competitively inhibits the binding of the second antibody to mature human TNF-α, where comparative binding specificity is determined by antibody-antibody competition assays in the presence of mature human TNF-α; and,
wherein when the antibody binds mature human TNF-α, the induction of tumor fibrin deposition is unaffected, and cytotoxicity, tumor regression and tumor receptor binding activities are inhibited.
278. Claim 278 .An antibody according to any one of claims 261-277, wherein the antibody is a humanized antibody.
279. Claim 279 .An antibody according to any one of claims 261-277, wherein the antibody is a chimeric antibody.
280. Claim 280 .A composition comprising an isolated single chain antibody that specifically binds to mature human TNF-α,
wherein when the antibody binds mature human TNF-α, the induction of endothelial procoagulant activity is inhibited,
wherein the isolated antibody competitively inhibits a second antibody or fragment thereof for specific binding to mature human TNF-α,
wherein the second antibody or fragment thereof binds to peptides having amino acid sequences 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
, 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
, 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 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
of the mature human TNF-α amino acid sequence.
281. Claim 281 .A composition according to claim 280 , wherein the antibody has no effect on the induction of tumor fibrin deposition activity.
282. Claim 282 .A composition comprising an antibody according to claim 280 , wherein the antibody inhibits tumor receptor binding.
283. Claim 283 .A composition comprising an antibody according to claim 282 , wherein the antibody inhibits cytotoxicity.
284. Claim 284 .A composition comprising an antibody according to claim 280 , wherein the antibody inhibits cytotoxicity.
285. Claim 285 .A composition comprising an antibody according to claim 284 , wherein the antibody inhibits tumor regression.
286. Claim 286 .A composition comprising an antibody according to claim 283 , wherein the antibody inhibits tumor regression.
287. Claim 287 .A composition comprising an antibody according to claim 282 , wherein the antibody inhibits tumor regression.
288. Claim 288 .A composition comprising an antibody according to claim 280 , wherein the antibody inhibits tumor regression.
289. Claim 289 .A composition according to claim 280 , wherein when the antibody binds mature human TNF-α, the induction of tumor fibrin deposition is unaffected, and cytotoxicity, tumor regression and tumor receptor binding activities are inhibited.
290. Claim 290 .A composition according to claim 280 , where comparative binding specificity between the antibody and the second antibody or fragment thereof is determined by antibody-antibody competition assays in the presence of mature human TNF-α.
291. Claim 291 .A composition comprising an antibody according to claim 290 , wherein the antibody inhibits tumor receptor binding.
292. Claim 292 .A composition comprising an antibody according to claim 291 , wherein the antibody inhibits cytotoxicity.
293. Claim 293 .A composition comprising an antibody according to claim 280 , wherein the antibody inhibits cytotoxicity.
294. Claim 294 .A composition comprising an antibody according to claim 292 , wherein the antibody inhibits tumor regression.
295. Claim 295 .A composition comprising an antibody according to claim 280 , wherein the antibody inhibits tumor regression.
296. Claim 296 .A composition according to claim 280 , wherein the antibody competitively inhibits the binding of the second antibody or fragment thereof to mature human TNF-α, where comparative binding specificity is determined by antibody-antibody competition assays in the presence of mature human TNF-α; and,
wherein when the antibody binds mature human TNF-α, the induction of tumor fibrin deposition is unaffected, and cytotoxicity, tumor regression and tumor receptor binding activities are inhibited.
297. Claim 297 .A composition according to any one of claims 280-296, wherein the antibody is a humanized antibody.
298. Claim 298 .A composition according to any one of claims 280-296, wherein the antibody is a chimeric antibody.
299. Claim 299 .An isolated single domain antibody or fragment thereof that specifically binds to mature human TNF-α,
wherein the antibody or fragment thereof competitively inhibits MAb 53 (accession No. 90012433) for specific binding to mature human TNF-α and,
wherein when the antibody or fragment thereof binds mature human TNF-α, the induction of tumor fibrin deposition is unaffected, and the induction of endothelial procoagulant activity, cytotoxicity, tumor regression and tumor receptor binding are inhibited.
300. Claim 300 .An antibody or fragment thereof according to claim 299 ,
wherein the antibody or fragment thereof competitively inhibits the binding of MAb 53 (accession No. 90012433) to mature human TNF-α, where comparative binding specificity is determined by antibody-antibody competition assays in the presence of mature human TNF-α.
301. Claim 301 .An antibody or fragment thereof according to claim 299 or 300 , wherein the antibody is a humanized antibody.
302. Claim 302 .An antibody or fragment thereof according to claim 299 or 300 , wherein the antibody is a chimeric antibody.
303. Claim 303 .A composition comprising an isolated single domain antibody or fragment thereof that specifically binds to mature human TNF-α,
wherein the antibody or fragment thereof competitively inhibits MAb 53 (accession No. 90012433) for specific binding to mature human TNF-α and,
wherein when the antibody or fragment thereof binds mature human TNF-α, the induction of tumor fibrin deposition is unaffected, and the induction of endothelial procoagulant activity, cytotoxicity, tumor regression and tumor receptor binding are inhibited.
304. Claim 304 .A composition according to claim 303 , wherein the antibody or fragment thereof competitively inhibits the binding of MAb 53 (accession No. 90012433) to mature human TNF-α, where comparative binding specificity is determined by antibody-antibody competition assays in the presence of mature human TNF-α.
305. Claim 305 .A composition according to claim 303 or 304 , wherein the antibody is a humanized antibody.
306. Claim 306 .A composition according to claim 303 or 304 , wherein the antibody is a chimeric antibody.
307. Claim 307 .An isolated single domain antibody or fragment thereof that specifically binds to mature human TNF-α,
wherein when the antibody or fragment thereof binds mature human TNF-α, the induction of endothelial procoagulant activity is inhibited,
wherein the isolated antibody or fragment thereof competitively inhibits a second antibody or fragment thereof for specific binding to mature human TNF-α; and,
wherein the second antibody or fragment thereof binds to peptides having amino acid sequences 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
, 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
, 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 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
of the mature human TNF-α amino acid sequence.
308. Claim 308 .An antibody or fragment thereof according to claim 307 , wherein the antibody or fragment thereof has no effect on the induction of tumor fibrin deposition activity.
309. Claim 309 .An antibody or fragment thereof according to claim 307 , wherein the antibody or fragment thereof inhibits tumor receptor binding.
310. Claim 310 .An antibody or fragment thereof according to claim 309 , wherein the antibody or fragment thereof inhibits cytotoxicity.
311. Claim 311 .An antibody or fragment thereof according to claim 307 , wherein the antibody or fragment thereof inhibits cytotoxicity.
312. Claim 312 .An antibody or fragment thereof according to claim 311 , wherein the antibody or fragment thereof inhibits tumor regression.
313. Claim 313 .An antibody or fragment thereof according to claim 310 , wherein the antibody or fragment thereof inhibits tumor regression.
314. Claim 314 .An antibody or fragment thereof according to claim 309 , wherein the antibody or fragment thereof inhibits tumor regression.
315. Claim 315 .An antibody or fragment thereof according to claim 307 , wherein the antibody or fragment thereof inhibits tumor regression.
316. Claim 316 .The antibody or fragment thereof according to claim 307 , wherein when the antibody or fragment thereof binds mature human TNF-α, the induction of tumor fibrin deposition is unaffected, and cytotoxicity, tumor regression and tumor receptor binding activities are inhibited.
317. Claim 317 .An antibody or fragment thereof according to claim 307 , where comparative binding specificity between the antibody or fragment thereof and the second antibody or fragment thereof is determined by antibody-antibody competition assays in the presence of mature human TNF-α.
318. Claim 318 .An antibody or fragment thereof according to claim 317 , wherein the antibody or fragment thereof inhibits tumor receptor binding.
319. Claim 319 .An antibody or fragment thereof according to claim 318 , wherein the antibody or fragment thereof inhibits cytotoxicity.
320. Claim 320 .An antibody or fragment thereof according to claim 317 , wherein the antibody or fragment thereof inhibits cytotoxicity.
321. Claim 321 .An antibody or fragment thereof according to claim 319 , wherein the antibody or fragment thereof inhibits tumor regression.
322. Claim 322 .An antibody or fragment thereof according to claim 317 , wherein the antibody or fragment thereof inhibits tumor regression.
323. Claim 323 .An antibody or fragment thereof according to claim 307 , wherein the antibody or fragment thereof competitively inhibits the binding of the second antibody or fragment thereof to mature human TNF-α, where comparative binding specificity is determined by antibody-antibody competition assays in the presence of mature human TNF-α; and,
wherein when the antibody or fragment thereof binds mature human TNF-α, the induction of tumor fibrin deposition is unaffected, and cytotoxicity, tumor regression and tumor receptor binding activities are inhibited.
324. Claim 324 .An antibody or fragment thereof according to any one of claims 307-323, wherein the antibody is a humanized antibody.
325. Claim 325 .An antibody or fragment thereof according to any one of claims 307-323, wherein the antibody is a chimeric antibody.
326. Claim 326 .A composition comprising an isolated single domain antibody or fragment thereof that specifically binds to mature human TNF-α,
wherein when the antibody or fragment thereof binds mature human TNF-α, the induction of endothelial procoagulant activity is inhibited,
wherein the antibody or fragment thereof competitively inhibits a second antibody or fragment thereof for specific binding to mature human TNF-α; and,
wherein the second antibody or fragment thereof binds to peptides having amino acid sequences 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
, 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
, 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 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
of the mature human TNF-α amino acid sequence.
327. Claim 327 .A composition according to claim 326 , wherein the antibody or fragment thereof has no effect on the induction of tumor fibrin deposition activity.
328. Claim 328 .A composition according to claim 326 , wherein the antibody or fragment thereof inhibits tumor receptor binding.
329. Claim 329 .A composition according to claim 328 , wherein the antibody or fragment thereof inhibits cytotoxicity.
330. Claim 330 .A composition according to claim 326 , wherein the antibody or fragment thereof inhibits cytotoxicity.
331. Claim 331 .A composition according to claim 330 , wherein the antibody or fragment thereof inhibits tumor regression.
332. Claim 332 .A composition according to claim 329 , wherein the antibody or fragment thereof inhibits tumor regression.
333. Claim 333 .A composition according to claim 328 , wherein the antibody or fragment thereof inhibits tumor regression.
334. Claim 334 .A composition according to claim 326 , wherein the antibody or fragment thereof inhibits tumor regression.
335. Claim 335 .A composition according to claim 326 , wherein when the antibody or fragment thereof binds mature human TNF-α, the induction of tumor fibrin deposition is unaffected, and cytotoxicity, tumor regression and tumor receptor binding activities are inhibited.
336. Claim 336 .A composition according to claim 326 , where comparative binding specificity between the antibody or fragment thereof and the second antibody or fragment thereof is determined by antibody-antibody competition assays in the presence of mature human TNF-α.
337. Claim 337 .An antibody or fragment thereof according to claim 336 , wherein the antibody or fragment thereof inhibits tumor receptor binding.
338. Claim 338 .An antibody or fragment thereof according to claim 337 , wherein the antibody or fragment thereof inhibits cytotoxicity.
339. Claim 339 .An antibody or fragment thereof according to claim 336 , wherein the antibody or fragment thereof inhibits cytotoxicity.
340. Claim 340 .An antibody or fragment thereof according to claim 338 , wherein the antibody or fragment thereof inhibits tumor regression.
341. Claim 341 .An antibody or fragment thereof according to claim 336 , wherein the antibody or fragment thereof inhibits tumor regression.
342. Claim 342 .A composition according to claim 326 , wherein the antibody or fragment thereof competitively inhibits the binding of the second antibody or fragment thereof to mature human TNF-α, where comparative binding specificity is determined by antibody-antibody competition assays in the presence of mature human TNF-α; and,
wherein when the antibody or fragment thereof binds mature human TNF-α, the induction of tumor fibrin deposition is unaffected, and cytotoxicity, tumor regression and tumor receptor binding activities are inhibited.
343. Claim 343 .A composition according to any one of claims 326-342, wherein the antibody is a humanized antibody.
344. Claim 344 .A composition according to any one of claims 326-342, wherein the antibody is a chimeric antibody.
345. Claim 345 .An isolated antibody or fragment thereof that specifically binds to mature human TNF-α,
wherein when the antibody or fragment thereof binds mature human TNF-α, the induction of endothelial procoagulant activity is inhibited,
wherein the antibody or fragment thereof competitively inhibits a second antibody or fragment thereof for specific binding to mature human TNF-α; and,
wherein the second antibody is Mab 53 (accession No. 90012433).
346. Claim 346 .An antibody or fragment thereof according to claim 345 , wherein the antibody is a monoclonal antibody.
347. Claim 347 .An antibody or fragment thereof according to claim 345 , wherein the antibody or fragment thereof has no effect on the induction of tumor fibrin deposition activity.
348. Claim 348 .An antibody or fragment thereof according to claim 345 , wherein the antibody or fragment thereof inhibits tumor receptor binding.
349. Claim 349 .An antibody or fragment thereof according to claim 348 , wherein the antibody or fragment thereof inhibits cytotoxicity.
350. Claim 350 .An antibody or fragment thereof according to claim 345 , wherein the antibody or fragment thereof inhibits cytotoxicity.
351. Claim 351 .An antibody or fragment thereof according to claim 350 , wherein the antibody or fragment thereof inhibits tumor regression.
352. Claim 352 .An antibody or fragment thereof according to claim 349 , wherein the antibody or fragment thereof inhibits tumor regression.
353. Claim 353 .An antibody or fragment thereof according to claim 348 , wherein the antibody or fragment thereof inhibits tumor regression.
354. Claim 354 .An antibody or fragment thereof according to claim 345 , wherein the antibody or fragment thereof inhibits tumor regression.
355. Claim 355 .An antibody or fragment thereof according to claim 345 , where comparative binding specificity between the antibody or fragment thereof and MAb 53 (accession No. 90012433) is determined by antibody-antibody competition assays in the presence of mature human TNF-α.
356. Claim 356 .An antibody or fragment thereof according to claim 355 , wherein the antibody or fragment thereof inhibits tumor receptor binding.
357. Claim 357 .An antibody or fragment thereof according to claim 356 , wherein the antibody or fragment thereof inhibits cytotoxicity.
358. Claim 358 .An antibody or fragment thereof according to claim 355 , wherein the antibody or fragment thereof inhibits cytotoxicity.
359. Claim 359 .An antibody or fragment thereof according to claim 357 , wherein the antibody or fragment thereof inhibits tumor regression.
360. Claim 360 .An antibody or fragment thereof according to claim 355 , wherein the antibody or fragment thereof inhibits tumor regression.
361. Claim 361 .An antibody or fragment thereof according to any one of claims 345-360, wherein the antibody is a humanized antibody.
362. Claim 362 .An antibody or fragment thereof according to any one of claims 345-360, wherein the antibody is a chimeric antibody.
363. Claim 363 .A composition comprising an isolated antibody or fragment thereof that specifically binds to mature human TNF-α,
wherein when the antibody or fragment thereof binds mature human TNF-α, the induction of endothelial procoagulant activity is inhibited,
wherein the antibody or fragment thereof competitively inhibits a second antibody or fragment thereof for specific binding to mature human TNF-α, and,
wherein the second antibody is Mab 53 (accession No. 90012433).
364. Claim 364 .A composition according to claim 363 , wherein the antibody is a monoclonal antibody.
365. Claim 365 .A composition according to claim 363 , wherein the antibody or fragment thereof has no effect on the induction of tumor fibrin deposition activity.
366. Claim 366 .A composition according to claim 363 , wherein the antibody or fragment thereof inhibits tumor receptor binding.
367. Claim 367 .A composition according to claim 366 , wherein the antibody or fragment thereof inhibits cytotoxicity.
368. Claim 368 .A composition according to claim 363 , wherein the antibody or fragment thereof inhibits cytotoxicity.
369. Claim 369 .A composition according to claim 368 , wherein the antibody or fragment thereof inhibits tumor regression.
370. Claim 370 .A composition according to claim 367 , wherein the antibody or fragment thereof inhibits tumor regression.
371. Claim 371 .A composition according to claim 366 , wherein the antibody or fragment thereof inhibits tumor regression.
372. Claim 372 .A composition according to claim 363 , wherein the antibody or fragment thereof inhibits tumor regression.
373. Claim 373 .A composition according to claim 363 , where comparative binding specificity between the antibody or fragment thereof and MAb 53 (accession No. 90012433) is determined by antibody-antibody competition assays in the presence of mature human TNF-α.
374. Claim 374 .A composition according to claim 373 , wherein the antibody or fragment thereof inhibits tumor receptor binding.
375. Claim 375 .A composition according to claim 374 , wherein the antibody or fragment thereof inhibits cytotoxicity.
376. Claim 376 .A composition according to claim 373 , wherein the antibody or fragment thereof inhibits cytotoxicity.
377. Claim 377 .A composition according to claim 375 , wherein the antibody or fragment thereof inhibits tumor regression.
378. Claim 378 .A composition according to claim 373 , wherein the antibody or fragment thereof inhibits tumor regression.
379. Claim 379 .A composition according to any one of claims 363-378, wherein the antibody is a humanized antibody.
380. Claim 380 .A composition according to any one of claims 363-378, wherein the antibody is a chimeric antibody.
381. Claim 381 .An isolated single chain antibody that specifically binds to mature human TNF-α,
wherein when the antibody binds mature human TNF-α, the induction of endothelial procoagulant activity is inhibited,
wherein the antibody competitively inhibits a second antibody or fragment thereof for specific binding to mature human TNF-α; and,
wherein the second antibody is Mab 53 (accession No. 90012433).
382. Claim 382 .An antibody according to claim 381 , wherein the antibody has no effect on the induction of tumor fibrin deposition activity.
383. Claim 383 .An antibody according to claim 381 , wherein the antibody inhibits tumor receptor binding.
384. Claim 384 .An antibody according to claim 383 , wherein the antibody inhibits cytotoxicity.
385. Claim 385 .An antibody according to claim 381 , wherein the antibody inhibits cytotoxicity.
386. Claim 386 .An antibody according to claim 385 , wherein the antibody inhibits tumor regression.
387. Claim 387 .An antibody according to claim 384 , wherein the antibody inhibits tumor regression.
388. Claim 388 .An antibody according to claim 383 , wherein the antibody inhibits tumor regression.
389. Claim 389 .An antibody according to claim 381 , wherein the antibody inhibits tumor regression.
390. Claim 390 .An antibody according to claim 381 , where comparative binding specificity between the antibody and MAb 53 (accession No. 90012433) is determined by antibody-antibody competition assays in the presence of mature human TNF-α.
391. Claim 391 .An antibody according to claim 390 , wherein the antibody inhibits tumor receptor binding.
392. Claim 392 .An antibody according to claim 391 , wherein the antibody inhibits cytotoxicity.
393. Claim 393 .An antibody according to claim 390 , wherein the antibody inhibits cytotoxicity.
394. Claim 394 .An antibody according to claim 392 , wherein the antibody inhibits tumor regression.
395. Claim 395 .An antibody according to claim 390 , wherein the antibody inhibits tumor regression.
396. Claim 396 .An antibody according to any one of claims 381-395, wherein the antibody is a humanized antibody.
397. Claim 397 .An antibody according to any one of claims 381-395, wherein the antibody is a chimeric antibody.
398. Claim 398 .A composition comprising an isolated single chain antibody that specifically binds to mature human TNF-α,
wherein when the antibody binds mature human TNF-α, the induction of endothelial procoagulant activity is inhibited,
wherein the isolated antibody competitively inhibits a second antibody or fragment thereof for specific binding to mature human TNF-α; and
wherein the second antibody is MAb 53 (accession No. 90012433).
399. Claim 399 .A composition according to claim 398 , wherein the antibody has no effect on the induction of tumor fibrin deposition activity.
400. Claim 400 .A composition according to claim 398 , wherein the antibody inhibits tumor receptor binding.
401. Claim 401 .A composition according to claim 400 , wherein the antibody inhibits cytotoxicity.
402. Claim 402 .A composition according to claim 398 , wherein the antibody inhibits cytotoxicity.
403. Claim 403 .A composition according to claim 408 , wherein the antibody inhibits tumor regression.
404. Claim 404 .A composition according to claim 401 , wherein the antibody inhibits tumor regression.
405. Claim 405 .A composition according to claim 400 , wherein the antibody inhibits tumor regression.
406. Claim 406 .A composition according to claim 398 , wherein the antibody inhibits tumor regression.
407. Claim 407 .A composition according to claim 398 , where comparative binding specificity between the antibody and MAb 53 (accession No. 90012433) is determined by antibody-antibody competition assays in the presence of mature human TNF-α.
408. Claim 408 .A composition according to claim 407 , wherein the antibody inhibits tumor receptor binding.
409. Claim 409 .A composition according to claim 408 , wherein the antibody inhibits cytotoxicity.
410. Claim 410 .A composition according to claim 407 , wherein the antibody inhibits cytotoxicity.
411. Claim 411 .A composition according to claim 409 , wherein the antibody inhibits tumor regression.
412. Claim 412 .A composition according to claim 407 , wherein the antibody inhibits tumor regression.
413. Claim 413 .A composition according to any one of claims 398-412, wherein the antibody is a humanized antibody.
414. Claim 414 .A composition according to any one of claims 398-412, wherein the antibody is a chimeric antibody.
415. Claim 415 .An isolated single domain antibody or fragment thereof that specifically binds to mature human TNF-α,
wherein when the antibody or fragment thereof binds mature human TNF-α, the induction of endothelial procoagulant activity is inhibited,
wherein the isolated antibody or fragment thereof competitively inhibits a second antibody or fragment thereof for specific binding to mature human TNF-α; and,
wherein the second antibody is Mab 53 (accession No. 90012433).
416. Claim 416 .An antibody or fragment thereof according to claim 415 , wherein the antibody or fragment thereof has no effect on the induction of tumor fibrin deposition activity.
417. Claim 417 .An antibody or fragment thereof according to claim 415 , wherein the antibody or fragment thereof inhibits tumor receptor binding.
418. Claim 418 .An antibody or fragment thereof according to claim 417 , wherein the antibody or fragment thereof inhibits cytotoxicity.
419. Claim 419 .An antibody or fragment thereof according to claim 415 , wherein the antibody or fragment thereof inhibits cytotoxicity.
420. Claim 420 .An antibody or fragment thereof according to claim 419 , wherein the antibody or fragment thereof inhibits tumor regression.
421. Claim 421 .An antibody or fragment thereof according to claim 418 , wherein the antibody or fragment thereof inhibits tumor regression.
422. Claim 422 .An antibody or fragment thereof according to claim 417 , wherein the antibody or fragment thereof inhibits tumor regression.
423. Claim 423 .An antibody or fragment thereof according to claim 415 , wherein the antibody or fragment thereof inhibits tumor regression.
424. Claim 424 .An antibody or fragment thereof according to claim 415 , where comparative binding specificity between the antibody or fragment thereof and MAb 53 (accession No. 90012433) is determined by antibody-antibody competition assays in the presence of mature human TNF-α.
425. Claim 425 .An antibody or fragment thereof according to claim 424 , wherein the antibody or fragment thereof inhibits tumor receptor binding.
426. Claim 426 .An antibody or fragment thereof according to claim 425 , wherein the antibody or fragment thereof inhibits cytotoxicity.
427. Claim 427 .An antibody or fragment thereof according to claim 424 , wherein the antibody or fragment thereof inhibits cytotoxicity.
428. Claim 428 .An antibody or fragment thereof according to claim 426 , wherein the antibody or fragment thereof inhibits tumor regression.
429. Claim 429 .An antibody or fragment thereof according to claim 424 , wherein the antibody or fragment thereof inhibits tumor regression.
430. Claim 430 .An antibody or fragment thereof according to any one of claims 415-429, wherein the antibody is a humanized antibody.
431. Claim 431 .An antibody or fragment thereof according to any one of claims 415-429, wherein the antibody is a chimeric antibody.
432. Claim 432 .A composition comprising an isolated single domain antibody or fragment thereof that specifically binds to mature human TNF-α,
wherein when the antibody or fragment thereof binds mature human TNF-α, the induction of endothelial procoagulant activity is inhibited,
wherein the antibody or fragment thereof competitively inhibits a second antibody or fragment thereof for specific binding to mature human TNF-α; and,
wherein the second antibody is Mab 53 (accession No. 90012433).
433. Claim 433 .A composition according to claim 432 , wherein the antibody or fragment thereof has no effect on the induction of tumor fibrin deposition activity.
434. Claim 434 .A composition according to claim 432 , wherein the antibody or fragment thereof inhibits tumor receptor binding.
435. Claim 435 .A composition according to claim 434 , wherein the antibody or fragment thereof inhibits cytotoxicity.
436. Claim 436 .A composition according to claim 432 , wherein the antibody or fragment thereof inhibits cytotoxicity.
437. Claim 437 .A composition according to claim 436 , wherein the antibody or fragment thereof inhibits tumor regression.
438. Claim 438 .A composition according to claim 435 , wherein the antibody or fragment thereof inhibits tumor regression.
439. Claim 439 .A composition according to claim 434 , wherein the antibody or fragment thereof inhibits tumor regression.
440. Claim 440 .A composition according to claim 432 , wherein the antibody or fragment thereof inhibits tumor regression.
441. Claim 441 .A composition according to claim 432 , where comparative binding specificity between the antibody or fragment thereof and MAb 53 (accession No. 90012433) is determined by antibody-antibody competition assays in the presence of mature human TNF-α.
442. Claim 442 .A composition according to claim 441 , wherein the antibody or fragment thereof inhibits tumor receptor binding.
443. Claim 443 .A composition according to claim 442 , wherein the antibody or fragment thereof inhibits cytotoxicity.
444. Claim 444 .A composition according to claim 441 , wherein the antibody or fragment thereof inhibits cytotoxicity.
445. Claim 445 .A composition according to claim 443 , wherein the antibody or fragment thereof inhibits tumor regression.
446. Claim 446 .A composition according to claim 441 , wherein the antibody or fragment thereof inhibits tumor regression.
447. Claim 447 .A composition according to any one of claims 432-446, wherein the antibody is a humanized antibody.
448. Claim 448 .A composition according to any one of claims 432-446, wherein the antibody is a chimeric antibody.Join the waitlist — get patent alerts
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