US 2026/0274977 A1Published application

Variant nucleic acid libraries for bcma

AssigneeTwist Bioscience Corporation

InventorAaron SATO

Life of this patent

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Abstract

Provided herein are methods and compositions relating to antibodies or antibody fragments that bind B cell maturation agent (BCMA), BCMA libraries having nucleic acids encoding for a scaffold comprising a BCMA domain and chimeric antigen receptor (CAR) comprising BCMA antibody or antigen-binding fragment thereof. BCMA libraries described herein encode for immunoglobulins such as antibodies.

Claims24

Dependent claims

An antibody or antigen-binding fragment thereof that binds B cell maturation agent (BCMA), wherein the antibody or antigen-binding fragment thereof comprises:

a) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
5 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
5, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
78 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
78, a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
151 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
151, a light chain complementary determining region 1 (LCDR1) comprising the amino acid sequence of SEQ ID NO:
297 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
297, a light chain complementary determining region 2 (LCDR2) comprising the amino acid sequence of SEQ ID NO:
324 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
324, and a light chain complementary determining region 3 (LCDR3) comprising the amino acid sequence of SEQ ID NO:
351 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
351;
b) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
6 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
6, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
79 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
79, a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
152 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
152, a light chain complementary determining region 1 (LCDR1) comprising the amino acid sequence of SEQ ID NO:
298 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
298, a light chain complementary determining region 2 (LCDR2) comprising the amino acid sequence of SEQ ID NO:
325 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
325, and a light chain complementary determining region 3 (LCDR3) comprising the amino acid sequence of SEQ ID NO:
352 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
352;
c) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
7 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
7, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
80 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
80, a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
153 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
153, a light chain complementary determining region 1 (LCDR1) comprising the amino acid sequence of SEQ ID NO:
299 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
299, a light chain complementary determining region 2 (LCDR2) comprising the amino acid sequence of SEQ ID NO:
326 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
326, and a light chain complementary determining region 3 (LCDR3) comprising the amino acid sequence of SEQ ID NO:
353 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
353;
d) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
8 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
8, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
81 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
81, a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
154 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
154, a light chain complementary determining region 1 (LCDR1) comprising the amino acid sequence of SEQ ID NO:
300 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
300, a light chain complementary determining region 2 (LCDR2) comprising the amino acid sequence of SEQ ID NO:
327 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
327, and a light chain complementary determining region 3 (LCDR3) comprising the amino acid sequence of SEQ ID NO:
354 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
354;
e) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
9 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
9, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
82 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
82, a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
155 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
155, a light chain complementary determining region 1 (LCDR1) comprising the amino acid sequence of SEQ ID NO:
301 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
301, a light chain complementary determining region 2 (LCDR2) comprising the amino acid sequence of SEQ ID NO:
328 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
328, and a light chain complementary determining region 3 (LCDR3) comprising the amino acid sequence of SEQ ID NO:
355 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
355;
f) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
10 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
10, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
83 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
83, a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
156 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
156, a light chain complementary determining region 1 (LCDR1) comprising the amino acid sequence of SEQ ID NO:
302 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
302, a light chain complementary determining region 2 (LCDR2) comprising the amino acid sequence of SEQ ID NO:
329 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
329, and a light chain complementary determining region 3 (LCDR3) comprising the amino acid sequence of SEQ ID NO:
356 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
356;
g) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
11 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
11, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
84 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
84, a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
157 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
157, a light chain complementary determining region 1 (LCDR1) comprising the amino acid sequence of SEQ ID NO:
303 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
303, a light chain complementary determining region 2 (LCDR2) comprising the amino acid sequence of SEQ ID NO:
330 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
330, and a light chain complementary determining region 3 (LCDR3) comprising the amino acid sequence of SEQ ID NO:
357 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
357;
h) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
12 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
12, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
85 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
85, a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
158 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
158, a light chain complementary determining region 1 (LCDR1) comprising the amino acid sequence of SEQ ID NO:
304 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
304, a light chain complementary determining region 2 (LCDR2) comprising the amino acid sequence of SEQ ID NO:
331 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
331, and a light chain complementary determining region 3 (LCDR3) comprising the amino acid sequence of SEQ ID NO:
358 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
358;
i) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
13 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
13, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
86 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
86, a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
159 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
159, a light chain complementary determining region 1 (LCDR1) comprising the amino acid sequence of SEQ ID NO:
305 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
305, a light chain complementary determining region 2 (LCDR2) comprising the amino acid sequence of SEQ ID NO:
332 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
332, and a light chain complementary determining region 3 (LCDR3) comprising the amino acid sequence of SEQ ID NO:
359 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
359;
j) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
14 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
14, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
87 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
87, a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
160 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
160, a light chain complementary determining region 1 (LCDR1) comprising the amino acid sequence of SEQ ID NO:
306 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
306, a light chain complementary determining region 2 (LCDR2) comprising the amino acid sequence of SEQ ID NO:
333 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
333, and a light chain complementary determining region 3 (LCDR3) comprising the amino acid sequence of SEQ ID NO:
360 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
360;
k) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
15 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
15, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
88 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
88, a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
161 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
161, a light chain complementary determining region 1 (LCDR1) comprising the amino acid sequence of SEQ ID NO:
307 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
307, a light chain complementary determining region 2 (LCDR2) comprising the amino acid sequence of SEQ ID NO:
334 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
334, and a light chain complementary determining region 3 (LCDR3) comprising the amino acid sequence of SEQ ID NO:
361 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
361;
l) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
16 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
16, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
89 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
89, a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
162 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
162, a light chain complementary determining region 1 (LCDR1) comprising the amino acid sequence of SEQ ID NO:
308 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
308, a light chain complementary determining region 2 (LCDR2) comprising the amino acid sequence of SEQ ID NO:
335 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
335, and a light chain complementary determining region 3 (LCDR3) comprising the amino acid sequence of SEQ ID NO:
362 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
362;
m) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
17 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
17, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
90 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
90, a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
163 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
163, a light chain complementary determining region 1 (LCDR1) comprising the amino acid sequence of SEQ ID NO:
309 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
309, a light chain complementary determining region 2 (LCDR2) comprising the amino acid sequence of SEQ ID NO:
336 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
336, and a light chain complementary determining region 3 (LCDR3) comprising the amino acid sequence of SEQ ID NO:
363 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
363;
n) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
18 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
18, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
91 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
91, a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
164 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
164, a light chain complementary determining region 1 (LCDR1) comprising the amino acid sequence of SEQ ID NO:
310 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
310, a light chain complementary determining region 2 (LCDR2) comprising the amino acid sequence of SEQ ID NO:
337 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
337, and a light chain complementary determining region 3 (LCDR3) comprising the amino acid sequence of SEQ ID NO:
364 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
364;
o) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
19 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
19, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
92 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
92, a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
165 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
165, a light chain complementary determining region 1 (LCDR1) comprising the amino acid sequence of SEQ ID NO:
311 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
311, a light chain complementary determining region 2 (LCDR2) comprising the amino acid sequence of SEQ ID NO:
338 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
338, and a light chain complementary determining region 3 (LCDR3) comprising the amino acid sequence of SEQ ID NO:
365 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
365;
p) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
20 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
20, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
93 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
93, a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
166 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
166, a light chain complementary determining region 1 (LCDR1) comprising the amino acid sequence of SEQ ID NO:
312 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
312, a light chain complementary determining region 2 (LCDR2) comprising the amino acid sequence of SEQ ID NO:
339 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
339, and a light chain complementary determining region 3 (LCDR3) comprising the amino acid sequence of SEQ ID NO:
366 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
366;
q) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
21 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
21, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
94 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
94, a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
167 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
167, a light chain complementary determining region 1 (LCDR1) comprising the amino acid sequence of SEQ ID NO:
313 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
313, a light chain complementary determining region 2 (LCDR2) comprising the amino acid sequence of SEQ ID NO:
340 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
340, and a light chain complementary determining region 3 (LCDR3) comprising the amino acid sequence of SEQ ID NO:
367 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
367;
r) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
22 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
22, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
95 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
95, a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
168 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
168, a light chain complementary determining region 1 (LCDR1) comprising the amino acid sequence of SEQ ID NO:
314 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
314, a light chain complementary determining region 2 (LCDR2) comprising the amino acid sequence of SEQ ID NO:
341 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
341, and a light chain complementary determining region 3 (LCDR3) comprising the amino acid sequence of SEQ ID NO:
368 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
368;
s) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
23 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
23, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
96 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
96, a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
169 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
169, a light chain complementary determining region 1 (LCDR1) comprising the amino acid sequence of SEQ ID NO:
315 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
315, a light chain complementary determining region 2 (LCDR2) comprising the amino acid sequence of SEQ ID NO:
342 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
342, and a light chain complementary determining region 3 (LCDR3) comprising the amino acid sequence of SEQ ID NO:
369 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
369;
t) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
24 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
24, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
97 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
97, a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
170 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
170, a light chain complementary determining region 1 (LCDR1) comprising the amino acid sequence of SEQ ID NO:
316 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
316, a light chain complementary determining region 2 (LCDR2) comprising the amino acid sequence of SEQ ID NO:
343 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
343, and a light chain complementary determining region 3 (LCDR3) comprising the amino acid sequence of SEQ ID NO:
370 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
370;
u) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
25 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
25, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
98 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
98, a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
171 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
171, a light chain complementary determining region 1 (LCDR1) comprising the amino acid sequence of SEQ ID NO:
317 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
317, a light chain complementary determining region 2 (LCDR2) comprising the amino acid sequence of SEQ ID NO:
344 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
344, and a light chain complementary determining region 3 (LCDR3) comprising the amino acid sequence of SEQ ID NO:
371 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
371;
v) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
26 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
26, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
99 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
99, a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
172 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
172, a light chain complementary determining region 1 (LCDR1) comprising the amino acid sequence of SEQ ID NO:
318 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
318, a light chain complementary determining region 2 (LCDR2) comprising the amino acid sequence of SEQ ID NO:
345 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
345, and a light chain complementary determining region 3 (LCDR3) comprising the amino acid sequence of SEQ ID NO:
372 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
372;
w) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
27 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
27, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
100 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
100, a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
173 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
173, a light chain complementary determining region 1 (LCDR1) comprising the amino acid sequence of SEQ ID NO:
319 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
319, a light chain complementary determining region 2 (LCDR2) comprising the amino acid sequence of SEQ ID NO:
346 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
346, and a light chain complementary determining region 3 (LCDR3) comprising the amino acid sequence of SEQ ID NO:
373 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
373;
x) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
28 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
28, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
101 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
101, a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
174 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
174, a light chain complementary determining region 1 (LCDR1) comprising the amino acid sequence of SEQ ID NO:
320 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
320, a light chain complementary determining region 2 (LCDR2) comprising the amino acid sequence of SEQ ID NO:
347 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
347, and a light chain complementary determining region 3 (LCDR3) comprising the amino acid sequence of SEQ ID NO:
374 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
374;
y) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
29 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
29, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
102 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
102, a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
175 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
175, a light chain complementary determining region 1 (LCDR1) comprising the amino acid sequence of SEQ ID NO:
321 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
321, a light chain complementary determining region 2 (LCDR2) comprising the amino acid sequence of SEQ ID NO:
348 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
348, and a light chain complementary determining region 3 (LCDR3) comprising the amino acid sequence of SEQ ID NO:
375 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
375;
z) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
30 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
30, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
103 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
103, a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
176 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
176, a light chain complementary determining region 1 (LCDR1) comprising the amino acid sequence of SEQ ID NO:
322 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
322, a light chain complementary determining region 2 (LCDR2) comprising the amino acid sequence of SEQ ID NO:
349 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
349, and a light chain complementary determining region 3 (LCDR3) comprising the amino acid sequence of SEQ ID NO:
376 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
376;
aa) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
31 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
31, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
104 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
104, a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
177 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
177, a light chain complementary determining region 1 (LCDR1) comprising the amino acid sequence of SEQ ID NO:
323 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
323, a light chain complementary determining region 2 (LCDR2) comprising the amino acid sequence of SEQ ID NO:
350 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
350, and a light chain complementary determining region 3 (LCDR3) comprising the amino acid sequence of SEQ ID NO:
377 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
377;
bb) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
32 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
32, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
105 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
105 and a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
178 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
178;
cc) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
33 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
33, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
106 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
106 and a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
179 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
179;
dd) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
34 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
34, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
107 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
107 and a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
180 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
180;
ee) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
35 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
35, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
108 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
108 and a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
181 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
181;
ff) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
36 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
36, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
109 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
109 and a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
182 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
182;
gg) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
37 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
37, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
110 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
110 and a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
183 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
183;
hh) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
38 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
38, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
111 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
111 and a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
184 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
184;
ii) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
39 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
39, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
112 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
112 and a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
185 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
185;
jj) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
40 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
40, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
113 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
113 and a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
186 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
186;
kk) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
41 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
41, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
114 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
114 and a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
187 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
187;
ll) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
42 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
42, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
115 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
115 and a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
188 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
188;
mm) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
43 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
43, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
116 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
116 and a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
189 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
189;
nn) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
44 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
44, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
117 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
117 and a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
190 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
190;
oo) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
45 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
45, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
118 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
118 and a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
191 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
191;
pp) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
46 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
46, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
119 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
119 and a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
192 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
192;
qq) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
47 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
47, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
120 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
120 and a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
193 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
193;
rr) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
48 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
48, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
121 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
121 a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
194 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
194;
ss) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
49 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
49, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
122 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
122 and a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
195 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
195;
tt) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
50 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
50, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
123 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
123 and a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
196 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
196;
uu) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
51 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
51, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
124 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
124 and a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
197 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
197;
vv) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
52 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
52, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
125 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
125 and a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
198 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
198;
ww) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
53 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
53, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
126 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
126 and a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
199 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
199;
xx) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
54 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
54, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
127 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
127 and a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
200 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
200;
yy) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
55 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
55, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
128 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
128 and a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
201 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
201;
zz) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
56 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
56, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
129 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
129 and a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
202 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
202;
aaa) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
57 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
57, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
130 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
130 and a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
203 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
203;
bbb) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
58 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
58, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
131 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
131 and a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
204 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
204;
ccc) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
59 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
59, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
132 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
132 and a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
205 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
205;
ddd) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
60 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
60, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
133 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
133 and a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
206 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
206;
eee) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
61 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
61, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
134 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
134 and a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
207 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
207;
fff) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
62 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
62, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
135 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
135 and a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
208 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
208;
ggg) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
63 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
63, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
136 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
136 a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
209 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
209;
hhh) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
64 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
64, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
137 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
137 and a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
210 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
210;
iii) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
65 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
65, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
138 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
138 a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
211 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
211;
jjj) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
66 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
66, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
139 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
139 a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
212 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
212;
kkk) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
67 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
67, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
140 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
140 and a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
213 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
213;
lll) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
68 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
68, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
141 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
141 and a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
214 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
214;
mmm) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
69 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
69, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
142 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
142 and a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
215 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
215;
nnn) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
70 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
70, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
143 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
143 and a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
216 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
216;
ooo) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
71 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
71, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
144 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
144 and a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
217 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
217;
ppp) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
72 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
72, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
145 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
145 and a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
218 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
218;
qqq) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
73 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
73, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
146 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
146 and a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
219 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
219;
rrr) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
74 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
74, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
147 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
147 a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
220 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
220;
sss) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
75 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
75, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
148 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
148 and a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
221 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
221;
ttt) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
76 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
76, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
149 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
149 a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
222 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
222;
or
uuu) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
77 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
77, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
150 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
150 a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
223 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
223.

671 more elements

Dependencies are inferred from the claim text.

Facts

Application: 19/166,855Filed 15 Mar 2024
Priority: 17 Mar 2023
Published: 17 Sep 2026
Term ends: Not estimatedThe source records don’t support an estimate.

Classification16 codes

C07K 16/2878
Against receptors, cell surface antigens or cell surface determinants: against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95
A61K 39/00
Medicinal preparations containing antigens or antibodies
A61K 40/11
Characterised by the cell type used: t-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer…
A61K 40/15
Characterised by the cell type used: natural-killer [NK] cells; Natural-killer T [NKT] cells

Family

Application63/490,988Us provisional application · filed 17 Mar 2023
US 2026/0274977 A1This patent

From the US filing history. Foreign family members aren’t listed.

Timeline

Citations

Open elsewhere

Abstract

An antibody or antigen-binding fragment thereof that binds B cell maturation agent (BCMA), wherein the antibody or antigen-binding fragment thereof comprises:

a) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
5 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
5, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
78 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
78, a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
151 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
151, a light chain complementary determining region 1 (LCDR1) comprising the amino acid sequence of SEQ ID NO:
297 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
297, a light chain complementary determining region 2 (LCDR2) comprising the amino acid sequence of SEQ ID NO:
324 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
324, and a light chain complementary determining region 3 (LCDR3) comprising the amino acid sequence of SEQ ID NO:
351 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
351;
b) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
6 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
6, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
79 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
79, a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
152 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
152, a light chain complementary determining region 1 (LCDR1) comprising the amino acid sequence of SEQ ID NO:
298 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
298, a light chain complementary determining region 2 (LCDR2) comprising the amino acid sequence of SEQ ID NO:
325 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
325, and a light chain complementary determining region 3 (LCDR3) comprising the amino acid sequence of SEQ ID NO:
352 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
352;
c) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
7 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
7, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
80 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
80, a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
153 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
153, a light chain complementary determining region 1 (LCDR1) comprising the amino acid sequence of SEQ ID NO:
299 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
299, a light chain complementary determining region 2 (LCDR2) comprising the amino acid sequence of SEQ ID NO:
326 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
326, and a light chain complementary determining region 3 (LCDR3) comprising the amino acid sequence of SEQ ID NO:
353 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
353;
d) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
8 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
8, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
81 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
81, a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
154 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
154, a light chain complementary determining region 1 (LCDR1) comprising the amino acid sequence of SEQ ID NO:
300 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
300, a light chain complementary determining region 2 (LCDR2) comprising the amino acid sequence of SEQ ID NO:
327 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
327, and a light chain complementary determining region 3 (LCDR3) comprising the amino acid sequence of SEQ ID NO:
354 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
354;
e) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
9 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
9, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
82 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
82, a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
155 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
155, a light chain complementary determining region 1 (LCDR1) comprising the amino acid sequence of SEQ ID NO:
301 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
301, a light chain complementary determining region 2 (LCDR2) comprising the amino acid sequence of SEQ ID NO:
328 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
328, and a light chain complementary determining region 3 (LCDR3) comprising the amino acid sequence of SEQ ID NO:
355 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
355;
f) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
10 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
10, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
83 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
83, a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
156 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
156, a light chain complementary determining region 1 (LCDR1) comprising the amino acid sequence of SEQ ID NO:
302 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
302, a light chain complementary determining region 2 (LCDR2) comprising the amino acid sequence of SEQ ID NO:
329 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
329, and a light chain complementary determining region 3 (LCDR3) comprising the amino acid sequence of SEQ ID NO:
356 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
356;
g) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
11 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
11, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
84 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
84, a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
157 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
157, a light chain complementary determining region 1 (LCDR1) comprising the amino acid sequence of SEQ ID NO:
303 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
303, a light chain complementary determining region 2 (LCDR2) comprising the amino acid sequence of SEQ ID NO:
330 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
330, and a light chain complementary determining region 3 (LCDR3) comprising the amino acid sequence of SEQ ID NO:
357 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
357;
h) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
12 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
12, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
85 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
85, a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
158 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
158, a light chain complementary determining region 1 (LCDR1) comprising the amino acid sequence of SEQ ID NO:
304 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
304, a light chain complementary determining region 2 (LCDR2) comprising the amino acid sequence of SEQ ID NO:
331 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
331, and a light chain complementary determining region 3 (LCDR3) comprising the amino acid sequence of SEQ ID NO:
358 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
358;
i) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
13 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
13, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
86 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
86, a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
159 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
159, a light chain complementary determining region 1 (LCDR1) comprising the amino acid sequence of SEQ ID NO:
305 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
305, a light chain complementary determining region 2 (LCDR2) comprising the amino acid sequence of SEQ ID NO:
332 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
332, and a light chain complementary determining region 3 (LCDR3) comprising the amino acid sequence of SEQ ID NO:
359 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
359;
j) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
14 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
14, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
87 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
87, a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
160 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
160, a light chain complementary determining region 1 (LCDR1) comprising the amino acid sequence of SEQ ID NO:
306 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
306, a light chain complementary determining region 2 (LCDR2) comprising the amino acid sequence of SEQ ID NO:
333 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
333, and a light chain complementary determining region 3 (LCDR3) comprising the amino acid sequence of SEQ ID NO:
360 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
360;
k) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
15 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
15, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
88 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
88, a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
161 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
161, a light chain complementary determining region 1 (LCDR1) comprising the amino acid sequence of SEQ ID NO:
307 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
307, a light chain complementary determining region 2 (LCDR2) comprising the amino acid sequence of SEQ ID NO:
334 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
334, and a light chain complementary determining region 3 (LCDR3) comprising the amino acid sequence of SEQ ID NO:
361 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
361;
l) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
16 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
16, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
89 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
89, a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
162 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
162, a light chain complementary determining region 1 (LCDR1) comprising the amino acid sequence of SEQ ID NO:
308 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
308, a light chain complementary determining region 2 (LCDR2) comprising the amino acid sequence of SEQ ID NO:
335 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
335, and a light chain complementary determining region 3 (LCDR3) comprising the amino acid sequence of SEQ ID NO:
362 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
362;
m) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
17 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
17, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
90 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
90, a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
163 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
163, a light chain complementary determining region 1 (LCDR1) comprising the amino acid sequence of SEQ ID NO:
309 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
309, a light chain complementary determining region 2 (LCDR2) comprising the amino acid sequence of SEQ ID NO:
336 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
336, and a light chain complementary determining region 3 (LCDR3) comprising the amino acid sequence of SEQ ID NO:
363 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
363;
n) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
18 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
18, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
91 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
91, a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
164 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
164, a light chain complementary determining region 1 (LCDR1) comprising the amino acid sequence of SEQ ID NO:
310 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
310, a light chain complementary determining region 2 (LCDR2) comprising the amino acid sequence of SEQ ID NO:
337 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
337, and a light chain complementary determining region 3 (LCDR3) comprising the amino acid sequence of SEQ ID NO:
364 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
364;
o) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
19 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
19, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
92 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
92, a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
165 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
165, a light chain complementary determining region 1 (LCDR1) comprising the amino acid sequence of SEQ ID NO:
311 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
311, a light chain complementary determining region 2 (LCDR2) comprising the amino acid sequence of SEQ ID NO:
338 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
338, and a light chain complementary determining region 3 (LCDR3) comprising the amino acid sequence of SEQ ID NO:
365 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
365;
p) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
20 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
20, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
93 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
93, a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
166 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
166, a light chain complementary determining region 1 (LCDR1) comprising the amino acid sequence of SEQ ID NO:
312 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
312, a light chain complementary determining region 2 (LCDR2) comprising the amino acid sequence of SEQ ID NO:
339 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
339, and a light chain complementary determining region 3 (LCDR3) comprising the amino acid sequence of SEQ ID NO:
366 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
366;
q) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
21 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
21, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
94 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
94, a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
167 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
167, a light chain complementary determining region 1 (LCDR1) comprising the amino acid sequence of SEQ ID NO:
313 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
313, a light chain complementary determining region 2 (LCDR2) comprising the amino acid sequence of SEQ ID NO:
340 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
340, and a light chain complementary determining region 3 (LCDR3) comprising the amino acid sequence of SEQ ID NO:
367 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
367;
r) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
22 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
22, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
95 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
95, a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
168 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
168, a light chain complementary determining region 1 (LCDR1) comprising the amino acid sequence of SEQ ID NO:
314 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
314, a light chain complementary determining region 2 (LCDR2) comprising the amino acid sequence of SEQ ID NO:
341 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
341, and a light chain complementary determining region 3 (LCDR3) comprising the amino acid sequence of SEQ ID NO:
368 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
368;
s) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
23 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
23, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
96 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
96, a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
169 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
169, a light chain complementary determining region 1 (LCDR1) comprising the amino acid sequence of SEQ ID NO:
315 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
315, a light chain complementary determining region 2 (LCDR2) comprising the amino acid sequence of SEQ ID NO:
342 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
342, and a light chain complementary determining region 3 (LCDR3) comprising the amino acid sequence of SEQ ID NO:
369 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
369;
t) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
24 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
24, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
97 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
97, a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
170 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
170, a light chain complementary determining region 1 (LCDR1) comprising the amino acid sequence of SEQ ID NO:
316 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
316, a light chain complementary determining region 2 (LCDR2) comprising the amino acid sequence of SEQ ID NO:
343 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
343, and a light chain complementary determining region 3 (LCDR3) comprising the amino acid sequence of SEQ ID NO:
370 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
370;
u) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
25 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
25, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
98 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
98, a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
171 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
171, a light chain complementary determining region 1 (LCDR1) comprising the amino acid sequence of SEQ ID NO:
317 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
317, a light chain complementary determining region 2 (LCDR2) comprising the amino acid sequence of SEQ ID NO:
344 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
344, and a light chain complementary determining region 3 (LCDR3) comprising the amino acid sequence of SEQ ID NO:
371 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
371;
v) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
26 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
26, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
99 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
99, a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
172 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
172, a light chain complementary determining region 1 (LCDR1) comprising the amino acid sequence of SEQ ID NO:
318 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
318, a light chain complementary determining region 2 (LCDR2) comprising the amino acid sequence of SEQ ID NO:
345 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
345, and a light chain complementary determining region 3 (LCDR3) comprising the amino acid sequence of SEQ ID NO:
372 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
372;
w) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
27 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
27, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
100 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
100, a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
173 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
173, a light chain complementary determining region 1 (LCDR1) comprising the amino acid sequence of SEQ ID NO:
319 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
319, a light chain complementary determining region 2 (LCDR2) comprising the amino acid sequence of SEQ ID NO:
346 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
346, and a light chain complementary determining region 3 (LCDR3) comprising the amino acid sequence of SEQ ID NO:
373 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
373;
x) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
28 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
28, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
101 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
101, a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
174 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
174, a light chain complementary determining region 1 (LCDR1) comprising the amino acid sequence of SEQ ID NO:
320 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
320, a light chain complementary determining region 2 (LCDR2) comprising the amino acid sequence of SEQ ID NO:
347 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
347, and a light chain complementary determining region 3 (LCDR3) comprising the amino acid sequence of SEQ ID NO:
374 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
374;
y) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
29 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
29, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
102 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
102, a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
175 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
175, a light chain complementary determining region 1 (LCDR1) comprising the amino acid sequence of SEQ ID NO:
321 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
321, a light chain complementary determining region 2 (LCDR2) comprising the amino acid sequence of SEQ ID NO:
348 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
348, and a light chain complementary determining region 3 (LCDR3) comprising the amino acid sequence of SEQ ID NO:
375 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
375;
z) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
30 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
30, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
103 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
103, a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
176 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
176, a light chain complementary determining region 1 (LCDR1) comprising the amino acid sequence of SEQ ID NO:
322 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
322, a light chain complementary determining region 2 (LCDR2) comprising the amino acid sequence of SEQ ID NO:
349 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
349, and a light chain complementary determining region 3 (LCDR3) comprising the amino acid sequence of SEQ ID NO:
376 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
376;
aa) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
31 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
31, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
104 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
104, a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
177 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
177, a light chain complementary determining region 1 (LCDR1) comprising the amino acid sequence of SEQ ID NO:
323 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
323, a light chain complementary determining region 2 (LCDR2) comprising the amino acid sequence of SEQ ID NO:
350 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
350, and a light chain complementary determining region 3 (LCDR3) comprising the amino acid sequence of SEQ ID NO:
377 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
377;
bb) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
32 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
32, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
105 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
105 and a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
178 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
178;
cc) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
33 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
33, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
106 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
106 and a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
179 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
179;
dd) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
34 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
34, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
107 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
107 and a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
180 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
180;
ee) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
35 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
35, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
108 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
108 and a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
181 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
181;
ff) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
36 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
36, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
109 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
109 and a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
182 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
182;
gg) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
37 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
37, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
110 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
110 and a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
183 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
183;
hh) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
38 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
38, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
111 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
111 and a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
184 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
184;
ii) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
39 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
39, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
112 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
112 and a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
185 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
185;
jj) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
40 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
40, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
113 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
113 and a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
186 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
186;
kk) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
41 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
41, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
114 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
114 and a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
187 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
187;
ll) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
42 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
42, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
115 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
115 and a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
188 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
188;
mm) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
43 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
43, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
116 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
116 and a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
189 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
189;
nn) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
44 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
44, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
117 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
117 and a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
190 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
190;
oo) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
45 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
45, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
118 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
118 and a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
191 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
191;
pp) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
46 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
46, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
119 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
119 and a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
192 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
192;
qq) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
47 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
47, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
120 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
120 and a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
193 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
193;
rr) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
48 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
48, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
121 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
121 a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
194 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
194;
ss) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
49 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
49, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
122 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
122 and a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
195 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
195;
tt) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
50 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
50, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
123 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
123 and a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
196 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
196;
uu) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
51 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
51, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
124 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
124 and a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
197 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
197;
vv) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
52 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
52, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
125 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
125 and a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
198 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
198;
ww) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
53 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
53, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
126 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
126 and a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
199 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
199;
xx) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
54 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
54, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
127 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
127 and a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
200 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
200;
yy) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
55 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
55, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
128 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
128 and a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
201 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
201;
zz) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
56 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
56, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
129 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
129 and a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
202 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
202;
aaa) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
57 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
57, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
130 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
130 and a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
203 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
203;
bbb) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
58 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
58, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
131 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
131 and a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
204 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
204;
ccc) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
59 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
59, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
132 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
132 and a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
205 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
205;
ddd) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
60 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
60, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
133 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
133 and a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
206 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
206;
eee) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
61 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
61, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
134 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
134 and a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
207 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
207;
fff) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
62 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
62, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
135 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
135 and a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
208 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
208;
ggg) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
63 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
63, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
136 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
136 a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
209 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
209;
hhh) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
64 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
64, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
137 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
137 and a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
210 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
210;
iii) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
65 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
65, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
138 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
138 a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
211 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
211;
jjj) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
66 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
66, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
139 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
139 a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
212 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
212;
kkk) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
67 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
67, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
140 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
140 and a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
213 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
213;
lll) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
68 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
68, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
141 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
141 and a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
214 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
214;
mmm) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
69 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
69, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
142 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
142 and a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
215 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
215;
nnn) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
70 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
70, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
143 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
143 and a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
216 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
216;
ooo) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
71 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
71, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
144 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
144 and a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
217 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
217;
ppp) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
72 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
72, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
145 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
145 and a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
218 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
218;
qqq) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
73 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
73, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
146 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
146 and a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
219 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
219;
rrr) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
74 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
74, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
147 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
147 a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
220 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
220;
sss) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
75 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
75, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
148 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
148 and a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
221 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
221;
ttt) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
76 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
76, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
149 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
149 a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
222 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
222;
or
uuu) a heavy chain complementary determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO:
77 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
77, a heavy chain complementary determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO:
150 or a functional variant thereof having on or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
150 a heavy chain complementary determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO:
223 or a functional variant thereof having one or two amino acid substitutions with respect to the amino acid sequence of SEQ ID NO:
223.

671 more elements

Facts

Application

19/166,855Filed 15 Mar 2024

Priority

17 Mar 2023

Published

17 Sep 2026

Term ends

Not estimatedThe source records don’t support an estimate.

Classification16 codes

C07K 16/2878
Against receptors, cell surface antigens or cell surface determinants: against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95
A61K 39/00
Medicinal preparations containing antigens or antibodies
A61K 40/11
Characterised by the cell type used: t-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer…
A61K 40/15
Characterised by the cell type used: natural-killer [NK] cells; Natural-killer T [NKT] cells