Therapeutic DLL4 binding proteins
First Claim
1. An isolated nucleic acid encoding a binding protein capable of binding human DLL4, wherein said binding protein comprises an antigen binding domain, comprising six complementarity determining regions (CDRs):
- CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3, wherein;
CDR-H1 is selected from the group consisting of;
residues 31-37 of SEQ ID NO;
1;
SEQ ID NO;
117;
SEQ ID NO;
121;
SEQ ID NO;
125;
SEQ ID NO;
129;
SEQ ID NO;
133;
SEQ ID NO;
137;
SEQ ID NO;
141;
SEQ ID NO;
145;
SEQ ID NO;
149;
SEQ ID NO;
153;
SEQ ID NO;
157;
SEQ ID NO;
161;
SEQ ID NO;
165;
SEQ ID NO;
169;
SEQ ID NO;
173;
SEQ ID NO;
177;
SEQ ID NO;
181;
SEQ ID NO;
185;
SEQ ID NO;
189;
SEQ ID NO;
193;
SEQ ID NO;
197;
SEQ ID NO;
201;
SEQ ID NO;
205;
SEQ ID NO;
209;
SEQ ID NO;
213;
residues 31-37 of SEQ ID NO;
334;
residues 31-37 of SEQ ID NO;
336;
residues 31-37 of SEQ ID NO;
338;
residues 31-37 of SEQ ID NO;
340;
residues 31-37 of SEQ ID NO;
342;
residues 31-37 of SEQ ID NO;
344;
residues 31-37 of SEQ ID NO;
346;
residues 31-37 of SEQ ID NO;
348;
residues 31-37 of SEQ ID NO;
350;
residues 31-37 of SEQ ID NO;
352;
residues 31-37 of SEQ ID NO;
354;
residues 31-37 of SEQ ID NO;
356;
residues 31-37 of SEQ ID NO;
358; and
residues 31-37 of SEQ ID NO;
360;
CDR-H2 is selected from the group consisting of;
residues 52-67 of SEQ ID NO;
1;
SEQ ID NO;
118;
SEQ ID NO;
122;
SEQ ID NO;
126;
SEQ ID NO;
130;
SEQ ID NO;
134;
SEQ ID NO;
138;
SEQ ID NO;
142;
SEQ ID NO;
146;
SEQ ID NO;
150;
SEQ ID NO;
154;
SEQ ID NO;
158;
SEQ ID NO;
162;
SEQ ID NO;
166;
SEQ ID NO;
170;
SEQ ID NO;
174;
SEQ ID NO;
178;
SEQ ID NO;
182;
SEQ ID NO;
186;
SEQ ID NO;
190;
SEQ ID NO;
194;
SEQ ID NO;
198;
SEQ ID NO;
202;
SEQ ID NO;
206;
SEQ ID NO;
210;
SEQ ID NO;
214;
residues 52-67 of SEQ ID NO;
334;
residues 52-67 of SEQ ID NO;
336;
residues 52-67 of SEQ ID NO;
338;
residues 52-67 of SEQ ID NO;
340;
residues 52-67 of SEQ ID NO;
342;
residues 52-67 of SEQ ID NO;
344;
residues 52-67 of SEQ ID NO;
346;
residues 52-67 of SEQ ID NO;
348;
residues 52-67 of SEQ ID NO;
350;
residues 52-67 of SEQ ID NO;
352;
residues 52-67 of SEQ ID NO;
354;
residues 52-67 of SEQ ID NO;
356;
residues 52-67 of SEQ ID NO;
358; and
residues 52-67 of SEQ ID NO;
360;
CDR-H3 is selected from the group consisting ofresidues 100-110 of SEQ ID NO;
1;
SEQ ID NO;
119;
SEQ ID NO;
123;
SEQ ID NO;
127;
SEQ ID NO;
131;
SEQ ID NO;
135;
SEQ ID NO;
139;
SEQ ID NO;
143;
SEQ ID NO;
147;
SEQ ID NO;
151;
SEQ ID NO;
155;
SEQ ID NO;
159;
SEQ ID NO;
163;
SEQ ID NO;
167;
SEQ ID NO;
171;
SEQ ID NO;
175;
SEQ ID NO;
179;
SEQ ID NO;
183;
SEQ ID NO;
187;
SEQ ID NO;
191;
SEQ ID NO;
195;
SEQ ID NO;
199;
SEQ ID NO;
203;
SEQ ID NO;
207;
SEQ ID NO;
211;
SEQ ID NO;
215;
residues 100-110 of SEQ ID NO;
334;
residues 100-110 of SEQ ID NO;
336;
residues 100-110 of SEQ ID NO;
338;
residues 100-110 of SEQ ID NO;
340;
residues 100-110 of SEQ ID NO;
342;
residues 100-110 of SEQ ID NO;
344;
residues 100-110 of SEQ ID NO;
346;
residues 100-110 of SEQ ID NO;
348;
residues 100-110 of SEQ ID NO;
350;
residues 100-110 of SEQ ID NO;
352;
residues 100-110 of SEQ ID NO;
354;
residues 100-110 of SEQ ID NO;
356;
residues 100-110 of SEQ ID NO;
358; and
residues 100-110 of SEQ ID NO;
360;
CDR-L1 is selected from the group consisting of;
residues 23-33 of SEQ ID NO;
111;
SEQ ID NO;
217;
SEQ ID NO;
221;
SEQ ID NO;
225;
SEQ ID NO;
229;
SEQ ID NO;
233;
SEQ ID NO;
237;
SEQ ID NO;
241;
SEQ ID NO;
245;
SEQ ID NO;
249;
SEQ ID NO;
253;
SEQ ID NO;
257;
SEQ ID NO;
261;
SEQ ID NO;
265;
SEQ ID NO;
269;
SEQ ID NO;
273;
SEQ ID NO;
277;
SEQ ID NO;
281;
SEQ ID NO;
285;
SEQ ID NO;
289;
SEQ ID NO;
293;
SEQ ID NO;
297;
SEQ ID NO;
301;
SEQ ID NO;
305;
SEQ ID NO;
309;
SEQ ID NO;
313;
residues 23-33 of SEQ ID NO;
335;
residues 23-33 of SEQ ID NO;
337;
residues 23-33 of SEQ ID NO;
339;
residues 23-33 of SEQ ID NO;
341;
residues 23-33 of SEQ ID NO;
343;
residues 24-34 of SEQ ID NO;
345;
residues 23-33 of SEQ ID NO;
347;
residues 24-34 of SEQ ID NO;
349;
residues 24-34 of SEQ ID NO;
351;
residues 24-34 of SEQ ID NO;
353;
residues 24-34 of SEQ ID NO;
355;
residues 23-33 of SEQ ID NO;
357;
residues 23-33 of SEQ ID NO;
359; and
residues 23-33 of SEQ ID NO;
361;
CDR-L2 is selected from the group consisting of;
residues 49-55 of SEQ ID NO;
111;
SEQ ID NO;
230;
SEQ ID NO;
234;
SEQ ID NO;
238;
SEQ ID NO;
242;
SEQ ID NO;
246;
SEQ ID NO;
250;
SEQ ID NO;
254;
SEQ ID NO;
258;
SEQ ID NO;
262;
SEQ ID NO;
266;
SEQ ID NO;
270;
SEQ ID NO;
218;
SEQ ID NO;
222;
SEQ ID NO;
226;
SEQ ID NO;
274;
SEQ ID NO;
278;
SEQ ID NO;
302;
SEQ ID NO;
294;
SEQ ID NO;
282;
SEQ ID NO;
290;
SEQ ID NO;
298;
SEQ ID NO;
286;
SEQ ID NO;
306;
SEQ ID NO;
310;
SEQ ID NO;
314;
residues 49-55 of SEQ ID NO;
335;
residues 49-55 of SEQ ID NO;
337;
residues 49-55 of SEQ ID NO;
339;
residues 49-55 of SEQ ID NO;
341;
residues 49-55 of SEQ ID NO;
343;
residues 50-56 of SEQ ID NO;
345;
residues 49-55 of SEQ ID NO;
347;
residues 50-56 of SEQ ID NO;
349;
residues 50-56 of SEQ ID NO;
351;
residues 50-56 of SEQ ID NO;
353;
residues 50-56 of SEQ ID NO;
355;
residues 49-55 of SEQ ID NO;
357;
residues 49-55 of SEQ ID NO;
359; and
residues 49-55 of SEQ ID NO;
361;
andCDR-L3 is selected from the group consisting of;
residues 88-96 of SEQ ID NO;
111;
SEQ ID NO;
231;
SEQ ID NO;
235;
SEQ ID NO;
239;
SEQ ID NO;
243;
SEQ ID NO;
247;
SEQ ID NO;
251;
SEQ ID NO;
255;
SEQ ID NO;
259;
SEQ ID NO;
263;
SEQ ID NO;
267;
SEQ ID NO;
271;
SEQ ID NO;
219;
SEQ ID NO;
223;
SEQ ID NO;
227;
SEQ ID NO;
275;
SEQ ID NO;
279;
SEQ ID NO;
303;
SEQ ID NO;
295;
SEQ ID NO;
283;
SEQ ID NO;
291;
SEQ ID NO;
299;
SEQ ID NO;
287;
SEQ ID NO;
307;
SEQ ID NO;
311;
SEQ ID NO;
315;
residues 88-96 of SEQ ID NO;
335;
residues 88-96 of SEQ ID NO;
337;
residues 88-96 of SEQ ID NO;
339;
residues 88-96 of SEQ ID NO;
341;
residues 88-96 of SEQ ID NO;
343;
residues 89-97 of SEQ ID NO;
345;
residues 88-96 of SEQ ID NO;
347;
residues 89-97 of SEQ ID NO;
349;
residues 89-97 of SEQ ID NO;
351;
residues 89-97 of SEQ ID NO;
353;
residues 89-97 of SEQ ID NO;
355;
residues 88-96 of SEQ ID NO;
357;
residues 88-96 of SEQ ID NO;
359; and
residues 88-96 of SEQ ID NO;
361.
0 Assignments
0 Petitions
Accused Products
Abstract
Improved DLL4 binding proteins are described, including antibodies, CDR-grafted antibodies, human antibodies, and DLL4 binding fragments thereof, proteins that bind DLL4 with high affinity, and DLL4 binding proteins that neutralize DLL4 activity. The DLL4 binding proteins are useful for treating or preventing cancers and tumors and especially for treating or preventing tumor angiogenesis, and/or other angiogenesis-dependent diseases such as ocular neovascularization, or angiogenesis-independent diseases characterized by aberrant DLL4 expression or activity such as autoimmune disorders including multiple sclerosis.
-
Citations
37 Claims
-
1. An isolated nucleic acid encoding a binding protein capable of binding human DLL4, wherein said binding protein comprises an antigen binding domain, comprising six complementarity determining regions (CDRs):
- CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3, wherein;
CDR-H1 is selected from the group consisting of; residues 31-37 of SEQ ID NO;
1;SEQ ID NO;
117;SEQ ID NO;
121;SEQ ID NO;
125;SEQ ID NO;
129;SEQ ID NO;
133;SEQ ID NO;
137;SEQ ID NO;
141;SEQ ID NO;
145;SEQ ID NO;
149;SEQ ID NO;
153;SEQ ID NO;
157;SEQ ID NO;
161;SEQ ID NO;
165;SEQ ID NO;
169;SEQ ID NO;
173;SEQ ID NO;
177;SEQ ID NO;
181;SEQ ID NO;
185;SEQ ID NO;
189;SEQ ID NO;
193;SEQ ID NO;
197;SEQ ID NO;
201;SEQ ID NO;
205;SEQ ID NO;
209;SEQ ID NO;
213;residues 31-37 of SEQ ID NO;
334;residues 31-37 of SEQ ID NO;
336;residues 31-37 of SEQ ID NO;
338;residues 31-37 of SEQ ID NO;
340;residues 31-37 of SEQ ID NO;
342;residues 31-37 of SEQ ID NO;
344;residues 31-37 of SEQ ID NO;
346;residues 31-37 of SEQ ID NO;
348;residues 31-37 of SEQ ID NO;
350;residues 31-37 of SEQ ID NO;
352;residues 31-37 of SEQ ID NO;
354;residues 31-37 of SEQ ID NO;
356;residues 31-37 of SEQ ID NO;
358; andresidues 31-37 of SEQ ID NO;
360;CDR-H2 is selected from the group consisting of; residues 52-67 of SEQ ID NO;
1;SEQ ID NO;
118;SEQ ID NO;
122;SEQ ID NO;
126;SEQ ID NO;
130;SEQ ID NO;
134;SEQ ID NO;
138;SEQ ID NO;
142;SEQ ID NO;
146;SEQ ID NO;
150;SEQ ID NO;
154;SEQ ID NO;
158;SEQ ID NO;
162;SEQ ID NO;
166;SEQ ID NO;
170;SEQ ID NO;
174;SEQ ID NO;
178;SEQ ID NO;
182;SEQ ID NO;
186;SEQ ID NO;
190;SEQ ID NO;
194;SEQ ID NO;
198;SEQ ID NO;
202;SEQ ID NO;
206;SEQ ID NO;
210;SEQ ID NO;
214;residues 52-67 of SEQ ID NO;
334;residues 52-67 of SEQ ID NO;
336;residues 52-67 of SEQ ID NO;
338;residues 52-67 of SEQ ID NO;
340;residues 52-67 of SEQ ID NO;
342;residues 52-67 of SEQ ID NO;
344;residues 52-67 of SEQ ID NO;
346;residues 52-67 of SEQ ID NO;
348;residues 52-67 of SEQ ID NO;
350;residues 52-67 of SEQ ID NO;
352;residues 52-67 of SEQ ID NO;
354;residues 52-67 of SEQ ID NO;
356;residues 52-67 of SEQ ID NO;
358; andresidues 52-67 of SEQ ID NO;
360;CDR-H3 is selected from the group consisting of residues 100-110 of SEQ ID NO;
1;SEQ ID NO;
119;SEQ ID NO;
123;SEQ ID NO;
127;SEQ ID NO;
131;SEQ ID NO;
135;SEQ ID NO;
139;SEQ ID NO;
143;SEQ ID NO;
147;SEQ ID NO;
151;SEQ ID NO;
155;SEQ ID NO;
159;SEQ ID NO;
163;SEQ ID NO;
167;SEQ ID NO;
171;SEQ ID NO;
175;SEQ ID NO;
179;SEQ ID NO;
183;SEQ ID NO;
187;SEQ ID NO;
191;SEQ ID NO;
195;SEQ ID NO;
199;SEQ ID NO;
203;SEQ ID NO;
207;SEQ ID NO;
211;SEQ ID NO;
215;residues 100-110 of SEQ ID NO;
334;residues 100-110 of SEQ ID NO;
336;residues 100-110 of SEQ ID NO;
338;residues 100-110 of SEQ ID NO;
340;residues 100-110 of SEQ ID NO;
342;residues 100-110 of SEQ ID NO;
344;residues 100-110 of SEQ ID NO;
346;residues 100-110 of SEQ ID NO;
348;residues 100-110 of SEQ ID NO;
350;residues 100-110 of SEQ ID NO;
352;residues 100-110 of SEQ ID NO;
354;residues 100-110 of SEQ ID NO;
356;residues 100-110 of SEQ ID NO;
358; andresidues 100-110 of SEQ ID NO;
360;CDR-L1 is selected from the group consisting of; residues 23-33 of SEQ ID NO;
111;SEQ ID NO;
217;SEQ ID NO;
221;SEQ ID NO;
225;SEQ ID NO;
229;SEQ ID NO;
233;SEQ ID NO;
237;SEQ ID NO;
241;SEQ ID NO;
245;SEQ ID NO;
249;SEQ ID NO;
253;SEQ ID NO;
257;SEQ ID NO;
261;SEQ ID NO;
265;SEQ ID NO;
269;SEQ ID NO;
273;SEQ ID NO;
277;SEQ ID NO;
281;SEQ ID NO;
285;SEQ ID NO;
289;SEQ ID NO;
293;SEQ ID NO;
297;SEQ ID NO;
301;SEQ ID NO;
305;SEQ ID NO;
309;SEQ ID NO;
313;residues 23-33 of SEQ ID NO;
335;residues 23-33 of SEQ ID NO;
337;residues 23-33 of SEQ ID NO;
339;residues 23-33 of SEQ ID NO;
341;residues 23-33 of SEQ ID NO;
343;residues 24-34 of SEQ ID NO;
345;residues 23-33 of SEQ ID NO;
347;residues 24-34 of SEQ ID NO;
349;residues 24-34 of SEQ ID NO;
351;residues 24-34 of SEQ ID NO;
353;residues 24-34 of SEQ ID NO;
355;residues 23-33 of SEQ ID NO;
357;residues 23-33 of SEQ ID NO;
359; andresidues 23-33 of SEQ ID NO;
361;CDR-L2 is selected from the group consisting of; residues 49-55 of SEQ ID NO;
111;SEQ ID NO;
230;SEQ ID NO;
234;SEQ ID NO;
238;SEQ ID NO;
242;SEQ ID NO;
246;SEQ ID NO;
250;SEQ ID NO;
254;SEQ ID NO;
258;SEQ ID NO;
262;SEQ ID NO;
266;SEQ ID NO;
270;SEQ ID NO;
218;SEQ ID NO;
222;SEQ ID NO;
226;SEQ ID NO;
274;SEQ ID NO;
278;SEQ ID NO;
302;SEQ ID NO;
294;SEQ ID NO;
282;SEQ ID NO;
290;SEQ ID NO;
298;SEQ ID NO;
286;SEQ ID NO;
306;SEQ ID NO;
310;SEQ ID NO;
314;residues 49-55 of SEQ ID NO;
335;residues 49-55 of SEQ ID NO;
337;residues 49-55 of SEQ ID NO;
339;residues 49-55 of SEQ ID NO;
341;residues 49-55 of SEQ ID NO;
343;residues 50-56 of SEQ ID NO;
345;residues 49-55 of SEQ ID NO;
347;residues 50-56 of SEQ ID NO;
349;residues 50-56 of SEQ ID NO;
351;residues 50-56 of SEQ ID NO;
353;residues 50-56 of SEQ ID NO;
355;residues 49-55 of SEQ ID NO;
357;residues 49-55 of SEQ ID NO;
359; andresidues 49-55 of SEQ ID NO;
361;and CDR-L3 is selected from the group consisting of; residues 88-96 of SEQ ID NO;
111;SEQ ID NO;
231;SEQ ID NO;
235;SEQ ID NO;
239;SEQ ID NO;
243;SEQ ID NO;
247;SEQ ID NO;
251;SEQ ID NO;
255;SEQ ID NO;
259;SEQ ID NO;
263;SEQ ID NO;
267;SEQ ID NO;
271;SEQ ID NO;
219;SEQ ID NO;
223;SEQ ID NO;
227;SEQ ID NO;
275;SEQ ID NO;
279;SEQ ID NO;
303;SEQ ID NO;
295;SEQ ID NO;
283;SEQ ID NO;
291;SEQ ID NO;
299;SEQ ID NO;
287;SEQ ID NO;
307;SEQ ID NO;
311;SEQ ID NO;
315;residues 88-96 of SEQ ID NO;
335;residues 88-96 of SEQ ID NO;
337;residues 88-96 of SEQ ID NO;
339;residues 88-96 of SEQ ID NO;
341;residues 88-96 of SEQ ID NO;
343;residues 89-97 of SEQ ID NO;
345;residues 88-96 of SEQ ID NO;
347;residues 89-97 of SEQ ID NO;
349;residues 89-97 of SEQ ID NO;
351;residues 89-97 of SEQ ID NO;
353;residues 89-97 of SEQ ID NO;
355;residues 88-96 of SEQ ID NO;
357;residues 88-96 of SEQ ID NO;
359; andresidues 88-96 of SEQ ID NO;
361. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37)
- CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3, wherein;
Specification