US 12,570,750 B2 · Antibodies that bind adenosine A2A receptors and methods of use thereof to treat cancer and neurological diseases

Abstract

Provided herein are methods and compositions relating to adenosine A2A receptor libraries having nucleic acids encoding for a scaffold comprising an adenosine A2A binding domain. adenosine A2A receptor libraries described herein encode for immunoglobulins including antibodies and single domain antibodies. Libraries described herein include variegated libraries comprising nucleic acids each encoding for a predetermined variant of at least one predetermined reference nucleic acid sequence. Further described herein are protein libraries generated when the nucleic acid libraries are translated. Further described herein are cell libraries expressing variegated nucleic acid libraries described herein.

An antibody or antibody fragment that binds adenosine A2A receptor, comprising an immunoglobulin heavy chain and an immunoglobulin light chain:

a) wherein the immunoglobulin heavy chain comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ:
6, a heavy chain CDR2 comprising the amino acid sequence of SEQ:
95, a heavy chain CDR3 comprising the amino acid sequence of SEQ:
184;
and wherein the immunoglobulin light chain comprises a light chain CDR1 comprising the amino acid sequence of SEQ:
273, a light chain CDR2 comprising the amino acid sequence of SEQ:
362, and a light chain CDR3 comprising the amino acid sequence of SEQ:
451;
b) wherein the immunoglobulin heavy chain comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ:
7, a heavy chain CDR2 comprising the amino acid sequence of SEQ:
96, a heavy chain CDR3 comprising the amino acid sequence of SEQ:
185;
and wherein the immunoglobulin light chain comprises a light chain CDR1 comprising the amino acid sequence of SEQ:
274, a light chain CDR2 comprising the amino acid sequence of SEQ:
363, and a light chain CDR3 comprising the amino acid sequence of SEQ:
452;
c) wherein the immunoglobulin heavy chain comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ:
8, a heavy chain CDR2 comprising the amino acid sequence of SEQ:
97, a heavy chain CDR3 comprising the amino acid sequence of SEQ:
186;
and wherein the immunoglobulin light chain comprises a light chain CDR1 comprising the amino acid sequence of SEQ:
275, a light chain CDR2 comprising the amino acid sequence of SEQ:
364, and a light chain CDR3 comprising the amino acid sequence of SEQ:
453;
d) wherein the immunoglobulin heavy chain comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ:
9, a heavy chain CDR2 comprising the amino acid sequence of SEQ:
98, a heavy chain CDR3 comprising the amino acid sequence of SEQ:
187;
and wherein the immunoglobulin light chain comprises a light chain CDR1 comprising the amino acid sequence of SEQ:
276, a light chain CDR2 comprising the amino acid sequence of SEQ:
365, and a light chain CDR3 comprising the amino acid sequence of SEQ:
454;
e) wherein the immunoglobulin heavy chain comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ:
10, a heavy chain CDR2 comprising the amino acid sequence of SEQ:
99, a heavy chain CDR3 comprising the amino acid sequence of SEQ:
188;
and wherein the immunoglobulin light chain comprises a light chain CDR1 comprising the amino acid sequence of SEQ:
277, a light chain CDR2 comprising the amino acid sequence of SEQ:
366, and a light chain CDR3 comprising the amino acid sequence of SEQ:
455;
f) wherein the immunoglobulin heavy chain comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ:
11, a heavy chain CDR2 comprising the amino acid sequence of SEQ:
100, a heavy chain CDR3 comprising the amino acid sequence of SEQ:
189;
and wherein the immunoglobulin light chain comprises a light chain CDR1 comprising the amino acid sequence of SEQ:
278, a light chain CDR2 comprising the amino acid sequence of SEQ:
367, and a light chain CDR3 comprising the amino acid sequence of SEQ:
456;
g) wherein the immunoglobulin heavy chain comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ:
12, a heavy chain CDR2 comprising the amino acid sequence of SEQ:
101, a heavy chain CDR3 comprising the amino acid sequence of SEQ:
190;
and wherein the immunoglobulin light chain comprises a light chain CDR1 comprising the amino acid sequence of SEQ:
279, a light chain CDR2 comprising the amino acid sequence of SEQ:
368, and a light chain CDR3 comprising the amino acid sequence of SEQ:
457;
h) wherein the immunoglobulin heavy chain comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ:
13, a heavy chain CDR2 comprising the amino acid sequence of SEQ:
102, a heavy chain CDR3 comprising the amino acid sequence of SEQ:
191;
and wherein the immunoglobulin light chain comprises a light chain CDR1 comprising the amino acid sequence of SEQ:
280, a light chain CDR2 comprising the amino acid sequence of SEQ:
369, and a light chain CDR3 comprising the amino acid sequence of SEQ:
458;
i) wherein the immunoglobulin heavy chain comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ:
14, a heavy chain CDR2 comprising the amino acid sequence of SEQ:
103, a heavy chain CDR3 comprising the amino acid sequence of SEQ:
192;
and wherein the immunoglobulin light chain comprises a light chain CDR1 comprising the amino acid sequence of SEQ:
281, a light chain CDR2 comprising the amino acid sequence of SEQ:
370, and a light chain CDR3 comprising the amino acid sequence of SEQ:
459;
j) wherein the immunoglobulin heavy chain comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ:
15, a heavy chain CDR2 comprising the amino acid sequence of SEQ:
104, a heavy chain CDR3 comprising the amino acid sequence of SEQ:
193;
and wherein the immunoglobulin light chain comprises a light chain CDR1 comprising the amino acid sequence of SEQ:
282, a light chain CDR2 comprising the amino acid sequence of SEQ:
371, and a light chain CDR3 comprising the amino acid sequence of SEQ:
460;
k) wherein the immunoglobulin heavy chain comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ:
16, a heavy chain CDR2 comprising the amino acid sequence of SEQ:
105, a heavy chain CDR3 comprising the amino acid sequence of SEQ:
194;
and wherein the immunoglobulin light chain comprises a light chain CDR1 comprising the amino acid sequence of SEQ:
283, a light chain CDR2 comprising the amino acid sequence of SEQ:
372, and a light chain CDR3 comprising the amino acid sequence of SEQ:
461;
l) wherein the immunoglobulin heavy chain comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ:
17, a heavy chain CDR2 comprising the amino acid sequence of SEQ:
106, a heavy chain CDR3 comprising the amino acid sequence of SEQ:
195;
and wherein the immunoglobulin light chain comprises a light chain CDR1 comprising the amino acid sequence of SEQ:
284, a light chain CDR2 comprising the amino acid sequence of SEQ:
373, and a light chain CDR3 comprising the amino acid sequence of SEQ:
462;
m) wherein the immunoglobulin heavy chain comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ:
18, a heavy chain CDR2 comprising the amino acid sequence of SEQ:
107, a heavy chain CDR3 comprising the amino acid sequence of SEQ:
196;
and wherein the immunoglobulin light chain comprises a light chain CDR1 comprising the amino acid sequence of SEQ:
285, a light chain CDR2 comprising the amino acid sequence of SEQ:
374, and a light chain CDR3 comprising the amino acid sequence of SEQ:
463;
n) wherein the immunoglobulin heavy chain comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ:
19, a heavy chain CDR2 comprising the amino acid sequence of SEQ:
108, a heavy chain CDR3 comprising the amino acid sequence of SEQ:
197;
and wherein the immunoglobulin light chain comprises a light chain CDR1 comprising the amino acid sequence of SEQ:
286, a light chain CDR2 comprising the amino acid sequence of SEQ:
375, and a light chain CDR3 comprising the amino acid sequence of SEQ:
464;
o) wherein the immunoglobulin heavy chain comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ:
20, a heavy chain CDR2 comprising the amino acid sequence of SEQ:
109, a heavy chain CDR3 comprising the amino acid sequence of SEQ:
198;
and wherein the immunoglobulin light chain comprises a light chain CDR1 comprising the amino acid sequence of SEQ:
287, a light chain CDR2 comprising the amino acid sequence of SEQ:
376, and a light chain CDR3 comprising the amino acid sequence of SEQ:
465;
p) wherein the immunoglobulin heavy chain comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ:
21, a heavy chain CDR2 comprising the amino acid sequence of SEQ:
110, a heavy chain CDR3 comprising the amino acid sequence of SEQ:
199;
and wherein the immunoglobulin light chain comprises a light chain CDR1 comprising the amino acid sequence of SEQ:
288, a light chain CDR2 comprising the amino acid sequence of SEQ:
377, and a light chain CDR3 comprising the amino acid sequence of SEQ:
466;
q) wherein the immunoglobulin heavy chain comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ:
22, a heavy chain CDR2 comprising the amino acid sequence of SEQ:
111, a heavy chain CDR3 comprising the amino acid sequence of SEQ:
200;
and wherein the immunoglobulin light chain comprises a light chain CDR1 comprising the amino acid sequence of SEQ:
289, a light chain CDR2 comprising the amino acid sequence of SEQ:
378, and a light chain CDR3 comprising the amino acid sequence of SEQ:
467;
r) wherein the immunoglobulin heavy chain comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ:
23, a heavy chain CDR2 comprising the amino acid sequence of SEQ:
112, a heavy chain CDR3 comprising the amino acid sequence of SEQ:
201;
and wherein the immunoglobulin light chain comprises a light chain CDR1 comprising the amino acid sequence of SEQ:
290, a light chain CDR2 comprising the amino acid sequence of SEQ:
379, and a light chain CDR3 comprising the amino acid sequence of SEQ:
468;
s) wherein the immunoglobulin heavy chain comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ:
24, a heavy chain CDR2 comprising the amino acid sequence of SEQ:
113, a heavy chain CDR3 comprising the amino acid sequence of SEQ:
202;
and wherein the immunoglobulin light chain comprises a light chain CDR1 comprising the amino acid sequence of SEQ:
291, a light chain CDR2 comprising the amino acid sequence of SEQ:
380, and a light chain CDR3 comprising the amino acid sequence of SEQ:
469;
t) wherein the immunoglobulin heavy chain comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ:
25, a heavy chain CDR2 comprising the amino acid sequence of SEQ:
114, a heavy chain CDR3 comprising the amino acid sequence of SEQ:
203;
and wherein the immunoglobulin light chain comprises a light chain CDR1 comprising the amino acid sequence of SEQ:
292, a light chain CDR2 comprising the amino acid sequence of SEQ:
381, and a light chain CDR3 comprising the amino acid sequence of SEQ:
470;
u) wherein the immunoglobulin heavy chain comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ:
26, a heavy chain CDR2 comprising the amino acid sequence of SEQ:
115, a heavy chain CDR3 comprising the amino acid sequence of SEQ:
204;
and wherein the immunoglobulin light chain comprises a light chain CDR1 comprising the amino acid sequence of SEQ:
293, a light chain CDR2 comprising the amino acid sequence of SEQ:
382, and a light chain CDR3 comprising the amino acid sequence of SEQ:
471;
v) wherein the immunoglobulin heavy chain comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ:
27, a heavy chain CDR2 comprising the amino acid sequence of SEQ:
116, a heavy chain CDR3 comprising the amino acid sequence of SEQ:
205;
and wherein the immunoglobulin light chain comprises a light chain CDR1 comprising the amino acid sequence of SEQ:
294, a light chain CDR2 comprising the amino acid sequence of SEQ:
383, and a light chain CDR3 comprising the amino acid sequence of SEQ:
472;
w) wherein the immunoglobulin heavy chain comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ:
28, a heavy chain CDR2 comprising the amino acid sequence of SEQ:
117, a heavy chain CDR3 comprising the amino acid sequence of SEQ:
206;
and wherein the immunoglobulin light chain comprises a light chain CDR1 comprising the amino acid sequence of SEQ:
295, a light chain CDR2 comprising the amino acid sequence of SEQ:
384, and a light chain CDR3 comprising the amino acid sequence of SEQ:
473;
x) wherein the immunoglobulin heavy chain comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ:
29, a heavy chain CDR2 comprising the amino acid sequence of SEQ:
118, a heavy chain CDR3 comprising the amino acid sequence of SEQ:
207;
and wherein the immunoglobulin light chain comprises a light chain CDR1 comprising the amino acid sequence of SEQ:
296, a light chain CDR2 comprising the amino acid sequence of SEQ:
385, and a light chain CDR3 comprising the amino acid sequence of SEQ:
474;
y) wherein the immunoglobulin heavy chain comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ:
30, a heavy chain CDR2 comprising the amino acid sequence of SEQ:
119, a heavy chain CDR3 comprising the amino acid sequence of SEQ:
208;
and wherein the immunoglobulin light chain comprises a light chain CDR1 comprising the amino acid sequence of SEQ:
297, a light chain CDR2 comprising the amino acid sequence of SEQ:
386, and a light chain CDR3 comprising the amino acid sequence of SEQ:
475;
z) wherein the immunoglobulin heavy chain comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ:
31, a heavy chain CDR2 comprising the amino acid sequence of SEQ:
120, a heavy chain CDR3 comprising the amino acid sequence of SEQ:
209;
and wherein the immunoglobulin light chain comprises a light chain CDR1 comprising the amino acid sequence of SEQ:
298, a light chain CDR2 comprising the amino acid sequence of SEQ:
387, and a light chain CDR3 comprising the amino acid sequence of SEQ:
476;
aa) wherein the immunoglobulin heavy chain comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ:
32, a heavy chain CDR2 comprising the amino acid sequence of SEQ:
121, a heavy chain CDR3 comprising the amino acid sequence of SEQ:
210;
and wherein the immunoglobulin light chain comprises a light chain CDR1 comprising the amino acid sequence of SEQ:
299, a light chain CDR2 comprising the amino acid sequence of SEQ:
388, and a light chain CDR3 comprising the amino acid sequence of SEQ:
477;
bb) wherein the immunoglobulin heavy chain comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ:
33, a heavy chain CDR2 comprising the amino acid sequence of SEQ:
122, a heavy chain CDR3 comprising the amino acid sequence of SEQ:
211;
and wherein the immunoglobulin light chain comprises a light chain CDR1 comprising the amino acid sequence of SEQ:
300, a light chain CDR2 comprising the amino acid sequence of SEQ:
389, and a light chain CDR3 comprising the amino acid sequence of SEQ:
478;
cc) wherein the immunoglobulin heavy chain comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ:
34, a heavy chain CDR2 comprising the amino acid sequence of SEQ:
123, a heavy chain CDR3 comprising the amino acid sequence of SEQ:
212;
and wherein the immunoglobulin light chain comprises a light chain CDR1 comprising the amino acid sequence of SEQ:
301, a light chain CDR2 comprising the amino acid sequence of SEQ:
390, and a light chain CDR3 comprising the amino acid sequence of SEQ:
479;
dd) wherein the immunoglobulin heavy chain comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ:
35, a heavy chain CDR2 comprising the amino acid sequence of SEQ:
124, a heavy chain CDR3 comprising the amino acid sequence of SEQ:
213;
and wherein the immunoglobulin light chain comprises a light chain CDR1 comprising the amino acid sequence of SEQ:
302, a light chain CDR2 comprising the amino acid sequence of SEQ:
391, and a light chain CDR3 comprising the amino acid sequence of SEQ:
480;
ee) wherein the immunoglobulin heavy chain comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ:
36, a heavy chain CDR2 comprising the amino acid sequence of SEQ:
125, a heavy chain CDR3 comprising the amino acid sequence of SEQ:
214;
and wherein the immunoglobulin light chain comprises a light chain CDR1 comprising the amino acid sequence of SEQ:
303, a light chain CDR2 comprising the amino acid sequence of SEQ:
392, and a light chain CDR3 comprising the amino acid sequence of SEQ:
481;
ff) wherein the immunoglobulin heavy chain comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ:
37, a heavy chain CDR2 comprising the amino acid sequence of SEQ:
126, a heavy chain CDR3 comprising the amino acid sequence of SEQ:
215;
and wherein the immunoglobulin light chain comprises a light chain CDR1 comprising the amino acid sequence of SEQ:
304, a light chain CDR2 comprising the amino acid sequence of SEQ:
393, and a light chain CDR3 comprising the amino acid sequence of SEQ:
482;
gg) wherein the immunoglobulin heavy chain comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ:
38, a heavy chain CDR2 comprising the amino acid sequence of SEQ:
127, a heavy chain CDR3 comprising the amino acid sequence of SEQ:
216;
and wherein the immunoglobulin light chain comprises a light chain CDR1 comprising the amino acid sequence of SEQ:
305, a light chain CDR2 comprising the amino acid sequence of SEQ:
394, and a light chain CDR3 comprising the amino acid sequence of SEQ:
483;
hh) wherein the immunoglobulin heavy chain comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ:
39, a heavy chain CDR2 comprising the amino acid sequence of SEQ:
128, a heavy chain CDR3 comprising the amino acid sequence of SEQ:
217;
and wherein the immunoglobulin light chain comprises a light chain CDR1 comprising the amino acid sequence of SEQ:
306, a light chain CDR2 comprising the amino acid sequence of SEQ:
395, and a light chain CDR3 comprising the amino acid sequence of SEQ:
484;
ii) wherein the immunoglobulin heavy chain comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ:
40, a heavy chain CDR2 comprising the amino acid sequence of SEQ:
129, a heavy chain CDR3 comprising the amino acid sequence of SEQ:
218;
and wherein the immunoglobulin light chain comprises a light chain CDR1 comprising the amino acid sequence of SEQ:
307, a light chain CDR2 comprising the amino acid sequence of SEQ:
396, and a light chain CDR3 comprising the amino acid sequence of SEQ:
485;
jj) wherein the immunoglobulin heavy chain comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ:
41, a heavy chain CDR2 comprising the amino acid sequence of SEQ:
130, a heavy chain CDR3 comprising the amino acid sequence of SEQ:
219;
and wherein the immunoglobulin light chain comprises a light chain CDR1 comprising the amino acid sequence of SEQ:
308, a light chain CDR2 comprising the amino acid sequence of SEQ:
397, and a light chain CDR3 comprising the amino acid sequence of SEQ:
486;
kk) wherein the immunoglobulin heavy chain comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ:
42, a heavy chain CDR2 comprising the amino acid sequence of SEQ:
131, a heavy chain CDR3 comprising the amino acid sequence of SEQ:
220;
and wherein the immunoglobulin light chain comprises a light chain CDR1 comprising the amino acid sequence of SEQ:
309, a light chain CDR2 comprising the amino acid sequence of SEQ:
398, and a light chain CDR3 comprising the amino acid sequence of SEQ:
487;
ll) wherein the immunoglobulin heavy chain comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ:
43, a heavy chain CDR2 comprising the amino acid sequence of SEQ:
132, a heavy chain CDR3 comprising the amino acid sequence of SEQ:
221;
and wherein the immunoglobulin light chain comprises a light chain CDR1 comprising the amino acid sequence of SEQ:
310, a light chain CDR2 comprising the amino acid sequence of SEQ:
399, and a light chain CDR3 comprising the amino acid sequence of SEQ:
488;
mm) wherein the immunoglobulin heavy chain comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ:
44, a heavy chain CDR2 comprising the amino acid sequence of SEQ:
133, a heavy chain CDR3 comprising the amino acid sequence of SEQ:
222;
and wherein the immunoglobulin light chain comprises a light chain CDR1 comprising the amino acid sequence of SEQ:
311, a light chain CDR2 comprising the amino acid sequence of SEQ:
400, and a light chain CDR3 comprising the amino acid sequence of SEQ:
489;
nn) wherein the immunoglobulin heavy chain comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ:
45, a heavy chain CDR2 comprising the amino acid sequence of SEQ:
134, a heavy chain CDR3 comprising the amino acid sequence of SEQ:
223;
and wherein the immunoglobulin light chain comprises a light chain CDR1 comprising the amino acid sequence of SEQ:
312, a light chain CDR2 comprising the amino acid sequence of SEQ:
401, and a light chain CDR3 comprising the amino acid sequence of SEQ:
490;
oo) wherein the immunoglobulin heavy chain comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ:
46, a heavy chain CDR2 comprising the amino acid sequence of SEQ:
135, a heavy chain CDR3 comprising the amino acid sequence of SEQ:
224;
and wherein the immunoglobulin light chain comprises a light chain CDR1 comprising the amino acid sequence of SEQ:
313, a light chain CDR2 comprising the amino acid sequence of SEQ:
402, and a light chain CDR3 comprising the amino acid sequence of SEQ:
491;
pp) wherein the immunoglobulin heavy chain comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ:
47, a heavy chain CDR2 comprising the amino acid sequence of SEQ:
136, a heavy chain CDR3 comprising the amino acid sequence of SEQ:
225;
and wherein the immunoglobulin light chain comprises a light chain CDR1 comprising the amino acid sequence of SEQ:
314, a light chain CDR2 comprising the amino acid sequence of SEQ:
403, and a light chain CDR3 comprising the amino acid sequence of SEQ:
492;
qq) wherein the immunoglobulin heavy chain comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ:
48, a heavy chain CDR2 comprising the amino acid sequence of SEQ:
137, a heavy chain CDR3 comprising the amino acid sequence of SEQ:
226;
and wherein the immunoglobulin light chain comprises a light chain CDR1 comprising the amino acid sequence of SEQ:
315, a light chain CDR2 comprising the amino acid sequence of SEQ:
404, and a light chain CDR3 comprising the amino acid sequence of SEQ:
493;
rr) wherein the immunoglobulin heavy chain comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ:
49, a heavy chain CDR2 comprising the amino acid sequence of SEQ:
138, a heavy chain CDR3 comprising the amino acid sequence of SEQ:
227;
and wherein the immunoglobulin light chain comprises a light chain CDR1 comprising the amino acid sequence of SEQ:
316, a light chain CDR2 comprising the amino acid sequence of SEQ:
405, and a light chain CDR3 comprising the amino acid sequence of SEQ:
494;
ss) wherein the immunoglobulin heavy chain comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ:
50, a heavy chain CDR2 comprising the amino acid sequence of SEQ:
139, a heavy chain CDR3 comprising the amino acid sequence of SEQ:
228;
and wherein the immunoglobulin light chain comprises a light chain CDR1 comprising the amino acid sequence of SEQ:
317, a light chain CDR2 comprising the amino acid sequence of SEQ:
406, and a light chain CDR3 comprising the amino acid sequence of SEQ:
495;
tt) wherein the immunoglobulin heavy chain comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ:
51, a heavy chain CDR2 comprising the amino acid sequence of SEQ:
140, a heavy chain CDR3 comprising the amino acid sequence of SEQ:
229;
and wherein the immunoglobulin light chain comprises a light chain CDR1 comprising the amino acid sequence of SEQ:
318, a light chain CDR2 comprising the amino acid sequence of SEQ:
407, and a light chain CDR3 comprising the amino acid sequence of SEQ:
496;
uu) wherein the immunoglobulin heavy chain comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ:
52, a heavy chain CDR2 comprising the amino acid sequence of SEQ:
141, a heavy chain CDR3 comprising the amino acid sequence of SEQ:
230;
and wherein the immunoglobulin light chain comprises a light chain CDR1 comprising the amino acid sequence of SEQ:
319, a light chain CDR2 comprising the amino acid sequence of SEQ:
408, and a light chain CDR3 comprising the amino acid sequence of SEQ:
497;
vv) wherein the immunoglobulin heavy chain comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ:
53, a heavy chain CDR2 comprising the amino acid sequence of SEQ:
142, a heavy chain CDR3 comprising the amino acid sequence of SEQ:
231;
and wherein the immunoglobulin light chain comprises a light chain CDR1 comprising the amino acid sequence of SEQ:
320, a light chain CDR2 comprising the amino acid sequence of SEQ:
409, and a light chain CDR3 comprising the amino acid sequence of SEQ:
498;
ww) wherein the immunoglobulin heavy chain comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ:
54, a heavy chain CDR2 comprising the amino acid sequence of SEQ:
143, a heavy chain CDR3 comprising the amino acid sequence of SEQ:
232;
and wherein the immunoglobulin light chain comprises a light chain CDR1 comprising the amino acid sequence of SEQ:
321, a light chain CDR2 comprising the amino acid sequence of SEQ:
410, and a light chain CDR3 comprising the amino acid sequence of SEQ:
499;
xx) wherein the immunoglobulin heavy chain comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ:
55, a heavy chain CDR2 comprising the amino acid sequence of SEQ:
144, a heavy chain CDR3 comprising the amino acid sequence of SEQ:
233;
and wherein the immunoglobulin light chain comprises a light chain CDR1 comprising the amino acid sequence of SEQ:
322, a light chain CDR2 comprising the amino acid sequence of SEQ:
411, and a light chain CDR3 comprising the amino acid sequence of SEQ:
500;
yy) wherein the immunoglobulin heavy chain comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ:
56, a heavy chain CDR2 comprising the amino acid sequence of SEQ:
145, a heavy chain CDR3 comprising the amino acid sequence of SEQ:
234;
and wherein the immunoglobulin light chain comprises a light chain CDR1 comprising the amino acid sequence of SEQ:
323, a light chain CDR2 comprising the amino acid sequence of SEQ:
412, and a light chain CDR3 comprising the amino acid sequence of SEQ:
501;
yy) wherein the immunoglobulin heavy chain comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ:
57, a heavy chain CDR2 comprising the amino acid sequence of SEQ:
146, a heavy chain CDR3 comprising the amino acid sequence of SEQ:
235;
and wherein the immunoglobulin light chain comprises a light chain CDR1 comprising the amino acid sequence of SEQ:
324, a light chain CDR2 comprising the amino acid sequence of SEQ:
413, and a light chain CDR3 comprising the amino acid sequence of SEQ:
502;
zz) wherein the immunoglobulin heavy chain comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ:
58, a heavy chain CDR2 comprising the amino acid sequence of SEQ:
147, a heavy chain CDR3 comprising the amino acid sequence of SEQ:
236;
and wherein the immunoglobulin light chain comprises a light chain CDR1 comprising the amino acid sequence of SEQ:
325, a light chain CDR2 comprising the amino acid sequence of SEQ:
414, and a light chain CDR3 comprising the amino acid sequence of SEQ:
503;
aaa) wherein the immunoglobulin heavy chain comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ:
59, a heavy chain CDR2 comprising the amino acid sequence of SEQ:
148, a heavy chain CDR3 comprising the amino acid sequence of SEQ:
237;
and wherein the immunoglobulin light chain comprises a light chain CDR1 comprising the amino acid sequence of SEQ:
326, a light chain CDR2 comprising the amino acid sequence of SEQ:
415, and a light chain CDR3 comprising the amino acid sequence of SEQ:
504;
bbb) wherein the immunoglobulin heavy chain comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ:
60, a heavy chain CDR2 comprising the amino acid sequence of SEQ:
149, a heavy chain CDR3 comprising the amino acid sequence of SEQ:
238;
and wherein the immunoglobulin light chain comprises a light chain CDR1 comprising the amino acid sequence of SEQ:
327, a light chain CDR2 comprising the amino acid sequence of SEQ:
416, and a light chain CDR3 comprising the amino acid sequence of SEQ:
505;
ccc) wherein the immunoglobulin heavy chain comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ:
61, a heavy chain CDR2 comprising the amino acid sequence of SEQ:
150, a heavy chain CDR3 comprising the amino acid sequence of SEQ:
239;
and wherein the immunoglobulin light chain comprises a light chain CDR1 comprising the amino acid sequence of SEQ:
328, a light chain CDR2 comprising the amino acid sequence of SEQ:
417, and a light chain CDR3 comprising the amino acid sequence of SEQ:
506;
ddd) wherein the immunoglobulin heavy chain comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ:
62, a heavy chain CDR2 comprising the amino acid sequence of SEQ:
151, a heavy chain CDR3 comprising the amino acid sequence of SEQ:
240;
and wherein the immunoglobulin light chain comprises a light chain CDR1 comprising the amino acid sequence of SEQ:
329, a light chain CDR2 comprising the amino acid sequence of SEQ:
418, and a light chain CDR3 comprising the amino acid sequence of SEQ:
507;
eee) wherein the immunoglobulin heavy chain comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ:
63, a heavy chain CDR2 comprising the amino acid sequence of SEQ:
152, a heavy chain CDR3 comprising the amino acid sequence of SEQ:
241;
and wherein the immunoglobulin light chain comprises a light chain CDR1 comprising the amino acid sequence of SEQ:
330, a light chain CDR2 comprising the amino acid sequence of SEQ:
419, and a light chain CDR3 comprising the amino acid sequence of SEQ:
508;
fff) wherein the immunoglobulin heavy chain comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ:
64, a heavy chain CDR2 comprising the amino acid sequence of SEQ:
153, a heavy chain CDR3 comprising the amino acid sequence of SEQ:
242;
and wherein the immunoglobulin light chain comprises a light chain CDR1 comprising the amino acid sequence of SEQ:
331, a light chain CDR2 comprising the amino acid sequence of SEQ:
420, and a light chain CDR3 comprising the amino acid sequence of SEQ:
509;
ggg) wherein the immunoglobulin heavy chain comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ:
65, a heavy chain CDR2 comprising the amino acid sequence of SEQ:
154, a heavy chain CDR3 comprising the amino acid sequence of SEQ:
243;
and wherein the immunoglobulin light chain comprises a light chain CDR1 comprising the amino acid sequence of SEQ:
332, a light chain CDR2 comprising the amino acid sequence of SEQ:
421, and a light chain CDR3 comprising the amino acid sequence of SEQ:
510;
hhh) wherein the immunoglobulin heavy chain comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ:
66, a heavy chain CDR2 comprising the amino acid sequence of SEQ:
155, a heavy chain CDR3 comprising the amino acid sequence of SEQ:
244;
and wherein the immunoglobulin light chain comprises a light chain CDR1 comprising the amino acid sequence of SEQ:
333, a light chain CDR2 comprising the amino acid sequence of SEQ:
422, and a light chain CDR3 comprising the amino acid sequence of SEQ:
511;
iii) wherein the immunoglobulin heavy chain comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ:
67, a heavy chain CDR2 comprising the amino acid sequence of SEQ:
156, a heavy chain CDR3 comprising the amino acid sequence of SEQ:
245;
and wherein the immunoglobulin light chain comprises a light chain CDR1 comprising the amino acid sequence of SEQ:
334, a light chain CDR2 comprising the amino acid sequence of SEQ:
423, and a light chain CDR3 comprising the amino acid sequence of SEQ:
512;
jjj) wherein the immunoglobulin heavy chain comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ:
68, a heavy chain CDR2 comprising the amino acid sequence of SEQ:
157, a heavy chain CDR3 comprising the amino acid sequence of SEQ:
246;
and wherein the immunoglobulin light chain comprises a light chain CDR1 comprising the amino acid sequence of SEQ:
335, a light chain CDR2 comprising the amino acid sequence of SEQ:
424, and a light chain CDR3 comprising the amino acid sequence of SEQ:
513;
kkk) wherein the immunoglobulin heavy chain comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ:
69, a heavy chain CDR2 comprising the amino acid sequence of SEQ:
158, a heavy chain CDR3 comprising the amino acid sequence of SEQ:
247;
and wherein the immunoglobulin light chain comprises a light chain CDR1 comprising the amino acid sequence of SEQ:
336, a light chain CDR2 comprising the amino acid sequence of SEQ:
425, and a light chain CDR3 comprising the amino acid sequence of SEQ:
514;
lll) wherein the immunoglobulin heavy chain comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ:
70, a heavy chain CDR2 comprising the amino acid sequence of SEQ:
159, a heavy chain CDR3 comprising the amino acid sequence of SEQ:
248;
and wherein the immunoglobulin light chain comprises a light chain CDR1 comprising the amino acid sequence of SEQ:
337, a light chain CDR2 comprising the amino acid sequence of SEQ:
426, and a light chain CDR3 comprising the amino acid sequence of SEQ:
515;
mmm) wherein the immunoglobulin heavy chain comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ:
71, a heavy chain CDR2 comprising the amino acid sequence of SEQ:
160, a heavy chain CDR3 comprising the amino acid sequence of SEQ:
249;
and wherein the immunoglobulin light chain comprises a light chain CDR1 comprising the amino acid sequence of SEQ:
338, a light chain CDR2 comprising the amino acid sequence of SEQ:
427, and a light chain CDR3 comprising the amino acid sequence of SEQ:
516;
nnnn) wherein the immunoglobulin heavy chain comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ:
72, a heavy chain CDR2 comprising the amino acid sequence of SEQ:
161, a heavy chain CDR3 comprising the amino acid sequence of SEQ:
250;
and wherein the immunoglobulin light chain comprises a light chain CDR1 comprising the amino acid sequence of SEQ:
339, a light chain CDR2 comprising the amino acid sequence of SEQ:
428, and a light chain CDR3 comprising the amino acid sequence of SEQ:
517;
ooo) wherein the immunoglobulin heavy chain comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ:
73, a heavy chain CDR2 comprising the amino acid sequence of SEQ:
162, a heavy chain CDR3 comprising the amino acid sequence of SEQ:
251;
and wherein the immunoglobulin light chain comprises a light chain CDR1 comprising the amino acid sequence of SEQ:
340, a light chain CDR2 comprising the amino acid sequence of SEQ:
429, and a light chain CDR3 comprising the amino acid sequence of SEQ:
518;
ppp) wherein the immunoglobulin heavy chain comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ:
74, a heavy chain CDR2 comprising the amino acid sequence of SEQ:
163, a heavy chain CDR3 comprising the amino acid sequence of SEQ:
252;
and wherein the immunoglobulin light chain comprises a light chain CDR1 comprising the amino acid sequence of SEQ:
341, a light chain CDR2 comprising the amino acid sequence of SEQ:
430, and a light chain CDR3 comprising the amino acid sequence of SEQ:
519;
qqq) wherein the immunoglobulin heavy chain comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ:
75, a heavy chain CDR2 comprising the amino acid sequence of SEQ:
164, a heavy chain CDR3 comprising the amino acid sequence of SEQ:
253;
and wherein the immunoglobulin light chain comprises a light chain CDR1 comprising the amino acid sequence of SEQ:
342, a light chain CDR2 comprising the amino acid sequence of SEQ:
431, and a light chain CDR3 comprising the amino acid sequence of SEQ:
520;
rrr) wherein the immunoglobulin heavy chain comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ:
76, a heavy chain CDR2 comprising the amino acid sequence of SEQ:
165, a heavy chain CDR3 comprising the amino acid sequence of SEQ:
254;
and wherein the immunoglobulin light chain comprises a light chain CDR1 comprising the amino acid sequence of SEQ:
343, a light chain CDR2 comprising the amino acid sequence of SEQ:
432, and a light chain CDR3 comprising the amino acid sequence of SEQ:
521;
sss) wherein the immunoglobulin heavy chain comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ:
77, a heavy chain CDR2 comprising the amino acid sequence of SEQ:
166, a heavy chain CDR3 comprising the amino acid sequence of SEQ:
255;
and wherein the immunoglobulin light chain comprises a light chain CDR1 comprising the amino acid sequence of SEQ:
344, a light chain CDR2 comprising the amino acid sequence of SEQ:
433, and a light chain CDR3 comprising the amino acid sequence of SEQ:
522;
ttt) wherein the immunoglobulin heavy chain comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ:
78, a heavy chain CDR2 comprising the amino acid sequence of SEQ:
167, a heavy chain CDR3 comprising the amino acid sequence of SEQ:
256;
and wherein the immunoglobulin light chain comprises a light chain CDR1 comprising the amino acid sequence of SEQ:
345, a light chain CDR2 comprising the amino acid sequence of SEQ:
434, and a light chain CDR3 comprising the amino acid sequence of SEQ:
523;
uuu) wherein the immunoglobulin heavy chain comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ:
79, a heavy chain CDR2 comprising the amino acid sequence of SEQ:
168, a heavy chain CDR3 comprising the amino acid sequence of SEQ:
257;
and wherein the immunoglobulin light chain comprises a light chain CDR1 comprising the amino acid sequence of SEQ:
346, a light chain CDR2 comprising the amino acid sequence of SEQ:
435, and a light chain CDR3 comprising the amino acid sequence of SEQ:
524;
vvv) wherein the immunoglobulin heavy chain comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ:
80, a heavy chain CDR2 comprising the amino acid sequence of SEQ:
169, a heavy chain CDR3 comprising the amino acid sequence of SEQ:
258;
and wherein the immunoglobulin light chain comprises a light chain CDR1 comprising the amino acid sequence of SEQ:
347, a light chain CDR2 comprising the amino acid sequence of SEQ:
436, and a light chain CDR3 comprising the amino acid sequence of SEQ:
525;
www) wherein the immunoglobulin heavy chain comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ:
81, a heavy chain CDR2 comprising the amino acid sequence of SEQ:
170, a heavy chain CDR3 comprising the amino acid sequence of SEQ:
259;
and wherein the immunoglobulin light chain comprises a light chain CDR1 comprising the amino acid sequence of SEQ:
348, a light chain CDR2 comprising the amino acid sequence of SEQ:
437, and a light chain CDR3 comprising the amino acid sequence of SEQ:
526;
xxx) wherein the immunoglobulin heavy chain comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ:
83, a heavy chain CDR2 comprising the amino acid sequence of SEQ:
172, a heavy chain CDR3 comprising the amino acid sequence of SEQ:
261;
and wherein the immunoglobulin light chain comprises a light chain CDR1 comprising the amino acid sequence of SEQ:
350, a light chain CDR2 comprising the amino acid sequence of SEQ:
439, and a light chain CDR3 comprising the amino acid sequence of SEQ:
528;
yyy) wherein the immunoglobulin heavy chain comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ:
84, a heavy chain CDR2 comprising the amino acid sequence of SEQ:
173, a heavy chain CDR3 comprising the amino acid sequence of SEQ:
262;
and wherein the immunoglobulin light chain comprises a light chain CDR1 comprising the amino acid sequence of SEQ:
351, a light chain CDR2 comprising the amino acid sequence of SEQ:
440, and a light chain CDR3 comprising the amino acid sequence of SEQ:
529;
zzz) wherein the immunoglobulin heavy chain comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ:
85, a heavy chain CDR2 comprising the amino acid sequence of SEQ:
174, a heavy chain CDR3 comprising the amino acid sequence of SEQ:
263;
and wherein the immunoglobulin light chain comprises a light chain CDR1 comprising the amino acid sequence of SEQ:
352, a light chain CDR2 comprising the amino acid sequence of SEQ:
441, and a light chain CDR3 comprising the amino acid sequence of SEQ:
530;
aaaa) wherein the immunoglobulin heavy chain comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ:
87, a heavy chain CDR2 comprising the amino acid sequence of SEQ:
176, a heavy chain CDR3 comprising the amino acid sequence of SEQ:
265;
and wherein the immunoglobulin light chain comprises a light chain CDR1 comprising the amino acid sequence of SEQ:
354, a light chain CDR2 comprising the amino acid sequence of SEQ:
443, and a light chain CDR3 comprising the amino acid sequence of SEQ:
532;
bbbb) wherein the immunoglobulin heavy chain comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ:
88, a heavy chain CDR2 comprising the amino acid sequence of SEQ:
177, a heavy chain CDR3 comprising the amino acid sequence of SEQ:
266;
and wherein the immunoglobulin light chain comprises a light chain CDR1 comprising the amino acid sequence of SEQ:
355, a light chain CDR2 comprising the amino acid sequence of SEQ:
444, and a light chain CDR3 comprising the amino acid sequence of SEQ:
533;
cccc) wherein the immunoglobulin heavy chain comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ:
89, a heavy chain CDR2 comprising the amino acid sequence of SEQ:
178, a heavy chain CDR3 comprising the amino acid sequence of SEQ:
267;
and wherein the immunoglobulin light chain comprises a light chain CDR1 comprising the amino acid sequence of SEQ:
356, a light chain CDR2 comprising the amino acid sequence of SEQ:
445, and a light chain CDR3 comprising the amino acid sequence of SEQ:
534;
dddd) wherein the immunoglobulin heavy chain comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ:
90, a heavy chain CDR2 comprising the amino acid sequence of SEQ:
179, a heavy chain CDR3 comprising the amino acid sequence of SEQ:
268;
and wherein the immunoglobulin light chain comprises a light chain CDR1 comprising the amino acid sequence of SEQ:
357, a light chain CDR2 comprising the amino acid sequence of SEQ:
446, and a light chain CDR3 comprising the amino acid sequence of SEQ:
535;
eeee) wherein the immunoglobulin heavy chain comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ:
91, a heavy chain CDR2 comprising the amino acid sequence of SEQ:
180, a heavy chain CDR3 comprising the amino acid sequence of SEQ:
269;
and wherein the immunoglobulin light chain comprises a light chain CDR1 comprising the amino acid sequence of SEQ:
358, a light chain CDR2 comprising the amino acid sequence of SEQ:
447, and a light chain CDR3 comprising the amino acid sequence of SEQ:
536;
ffff) wherein the immunoglobulin heavy chain comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ:
92, a heavy chain CDR2 comprising the amino acid sequence of SEQ:
181, a heavy chain CDR3 comprising the amino acid sequence of SEQ:
270;
and wherein the immunoglobulin light chain comprises a light chain CDR1 comprising the amino acid sequence of SEQ:
359, a light chain CDR2 comprising the amino acid sequence of SEQ:
448, and a light chain CDR3 comprising the amino acid sequence of SEQ:
537;
gggg) wherein the immunoglobulin heavy chain comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ:
93, a heavy chain CDR2 comprising the amino acid sequence of SEQ:
182, a heavy chain CDR3 comprising the amino acid sequence of SEQ:
271;
and wherein the immunoglobulin light chain comprises a light chain CDR1 comprising the amino acid sequence of SEQ:
360, a light chain CDR2 comprising the amino acid sequence of SEQ:
449, and a light chain CDR3 comprising the amino acid sequence of SEQ:
538;
or
hhhh) wherein the immunoglobulin heavy chain comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ:
94, a heavy chain CDR2 comprising the amino acid sequence of SEQ:
183, a heavy chain CDR3 comprising the amino acid sequence of SEQ:
272;
and wherein the immunoglobulin light chain comprises a light chain CDR1 comprising the amino acid sequence of SEQ:
361, a light chain CDR2 comprising the amino acid sequence of SEQ:
450, and a light chain CDR3 comprising the amino acid sequence of SEQ:
539.

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Antibodies that bind adenosine A2A receptors and methods of use thereof to treat cancer and neurological diseases

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Antibodies that bind adenosine A2A receptors and methods of use thereof to treat cancer and neurological diseases

Life of this patent

Abstract

Claims11