US 2024/0368269 A1 · ANTI-DLL3 ANTIBODIES AND USES THEREOF

Anti-dll3 antibodies and uses thereof

AssigneesMemorial Sloan Kettering Cancer Center, Sloan-Kettering Institute for Cancer Research, Memorial Hospital for Cancer and Allied Diseases, Tri-Institutional Therapeutics Discovery Institute, Inc.

InventorsJohn T. Poirier, Charles Rudin, Jason Lewis, Abdul Khan, David Andrew, Xinlei Chen, Ivo C. Lorenz, Kathryn M. Tully, Salomon Tendler

Life of this patent

Estimating the term…

Abstract

The presently disclosed subject matter provides antibodies or antigen-binding fragments thereof that bind to DLL3 and methods of using such antibodies or antigen-binding fragments thereof same.

Claims21

Dependent claims

-108. (canceled)

An anti-DLL3 antibody or an antigen-binding fragment thereof, comprising:

a) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
1, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
2, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
3;
and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
4, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
5, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
6;
b) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
11, a CDR2 comprising an amino acid sequence set forth in SEQ ID NO:
12, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
13;
and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
14, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
15, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
16;
c) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
21, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
2, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
22;
and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
4, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
5, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
23;
d) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
28, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
29;
and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
30;
and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
31, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
32, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
33;
e) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
21, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
38, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
39;
and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
40, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
5, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
41;
f) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
46, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
47, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
48;
a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
49, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
50, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
51;
g) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
21, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
2, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
56;
and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
57, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
58, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
59;
h) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
21, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
2, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
64;
a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
4, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
5, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
65;
i) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
70, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
71, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
72;
and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
73, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
74, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
75;
j) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
21, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
80, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
81;
and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
57, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
58, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
82;
k) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
87, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
88, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
89;
and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
90, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
216, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
91;
l) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
96, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
97, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
98;
a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
99, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
100, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
101;
m) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
21, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
106, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
107;
and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
57, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
58, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
82;
n) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
21, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
106, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
107;
and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
4, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
5, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
112;
o) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
96, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
115, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
116;
and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
117, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
100, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
118;
p) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
21, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
2, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
123;
and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
124, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
58, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
125;
q) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
21, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
2, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
123;
and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
124, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
58, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
125;
r) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
21, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
2, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
56;
and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
57, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
58, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
130;
s) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
135, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
136, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
137;
and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
138, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
139, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
140;
t) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
21, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
2, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
145;
and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
57, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
146, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
125;
u) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
151, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
2, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
152;
and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
57, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
58, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
82;
v) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
21, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
2, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
123;
and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
124, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
58, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
59;
w) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
11, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
136, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
161;
and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
73, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
74, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
162;
or
x) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
96, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
167, a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
168;
and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
169, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
170, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
171.

191 more elements

A host cell comprising a nucleic acid encoding an anti-DLL3antibody or antigen-binding fragment thereof, wherein the anti-DLL3antibody or antigen-binding fragment thereof comprises:

a) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
1, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
2, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
3;
and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
4, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
5, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
6;
b) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
11, a CDR2 comprising an amino acid sequence set forth in SEQ ID NO:
12, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
13;
and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
14, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
15, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
16;
c) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
21, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
2, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
22;
and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
4, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
5, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
23;
d) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
28, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
29;
and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
30;
and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
31, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
32, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
33;
e) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
21, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
38, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
39;
and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
40, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
5, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
41;
f) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
46, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
47, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
48;
a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
49, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
50, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
51;
g) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
21, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
2, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
56;
and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
57, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
58, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
59;
h) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
21, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
2, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
64;
a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
4, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
5, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
65;
i) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
70, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
71, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
72;
and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
73, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
74, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
75;
j) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
21, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
80, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
81;
and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
57, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
58, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
82;
k) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
87, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
88, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
89;
and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
90, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
216, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
91;
l) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
96, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
97, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
98;
a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
99, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
100, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
101;
m) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
21, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
106, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
107;
and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
57, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
58, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
82;
n) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
21, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
106, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
107;
and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
4, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
5, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
112;
o) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
96, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
115, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
116;
and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
117, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
100, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
118;
p) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
21, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
2, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
123;
and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
124, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
58, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
125;
q) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
21, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
2, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
123;
and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
124, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
58, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
125;
r) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
21, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
2, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
56;
and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
57, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
58, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
130;
s) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
135, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
136, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
137;
and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
138, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
139, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
140;
t) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
21, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
2, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
145;
and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
57, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
146, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
125;
u) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
151, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
2, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
152;
and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
57, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
58, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
82;
v) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
21, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
2, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
123;
and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
124, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
58, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
59;
w) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
11, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
136, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
161;
and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
73, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
74, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
162;
or
x) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
96, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
167, a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
168;
and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
169, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
170, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
171.

191 more elements

An immunoconjugate comprising an anti-DLL3 antibody or antigen-binding fragment thereof linked to a therapeutic agent, wherein the anti-DLL3 antibody or antigen-binding fragment thereof comprises:

a) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
21, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
183, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
184;
and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
185, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
50, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
186;
b) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
191, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
192, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
193;
and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
194, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
195, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
196;
c) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
11, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
201, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
202;
and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
4, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
5, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
203;
or
d) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
208, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
209, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
210;
and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
57, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
58, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
211.

30 more elements

A pharmaceutical composition comprising:

A) an immunoconjugate comprising an anti-DLL3 antibody or antigen-binding fragment thereof linked to a therapeutic agent;
and
B) a pharmaceutically acceptable carrier;
wherein the anti-DLL3 antibody or antigen-binding fragment thereof comprises:
a) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
21, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
183, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
184;
and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
185, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
50, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
186;
b) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
191, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
192, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
193;
and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
194, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
195, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
196;
c) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
11, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
201, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
202;
and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
4, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
5, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
203;
or
d) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
208, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
209, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
210;
and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
57, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
58, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
211.

34 more elements

A method of treating or ameliorating a disease or disorder associated with DLL3 in a subject, comprising administering to the subject:

(A) an immunoconjugate comprising an anti-DLL3 antibody or antigen-binding fragment thereof linked to a therapeutic agent;
or
(B) a pharmaceutical composition thereof,
wherein the anti-DLL3antibody or antigen-binding fragment thereof comprises:
a) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
1, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
2, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
3;
and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
4, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
5, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
6;
b) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
11, a CDR2 comprising an amino acid sequence set forth in SEQ ID NO:
12, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
13;
and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
14, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
15, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
16;
c) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
21, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
2, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
22;
and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
4, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
5, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
23;
d) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
28, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
29;
and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
30;
and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
31, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
32, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
33;
e) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
21, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
38, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
39;
and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
40, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
5, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
41;
f) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
46, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
47, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
48;
a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
49, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
50, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
51;
g) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
21, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
2, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
56;
and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
57, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
58, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
59;
h) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
21, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
2, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
64;
a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
4, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
5, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
65;
i) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
70, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
71, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
72;
and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
73, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
74, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
75;
j) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
21, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
80, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
81;
and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
57, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
58, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
82;
k) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
87, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
88, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
89;
and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
90, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
216, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
91;
l) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
96, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
97, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
98;
a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
99, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
100, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
101;
m) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
21, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
106, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
107;
and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
57, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
58, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
82;
n) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
21, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
106, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
107;
and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
4, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
5, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
112;
o) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
96, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
115, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
116;
and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
117, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
100, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
118;
p) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
21, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
2, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
123;
and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
124, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
58, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
125;
q) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
21, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
2, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
123;
and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
124, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
58, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
125;
r) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
21, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
2, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
56;
and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
57, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
58, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
130;
s) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
135, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
136, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
137;
and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
138, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
139, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
140;
t) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
21, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
2, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
145;
and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
57, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
146, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
125;
u) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
151, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
2, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
152;
and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
57, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
58, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
82;
v) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
21, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
2, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
123;
and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
124, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
58, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
59;
w) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
11, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
136, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
161;
and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
73, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
74, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
162;
or
x) a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
96, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
167, a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
168;
and a light chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
169, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
170, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
171.

195 more elements

Dependencies are inferred from the claim text.

Facts

Application

18/589,762Filed 28 Feb 2024

Priority

2 Sep 2021

Published

7 Nov 2024

Term ends

Not estimatedThe source records don’t support an estimate.

Classification19 codes

C07K 16/28
Against material from animals or humans: against receptors, cell surface antigens or cell surface determinants
A61K 51/1027
Antibodies or immunoglobulins; Fragments thereof , the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised…
A61K 51/1054
Against animal or human tumor cells or tumor cell determinants: the tumor cell being from lung
A61K 51/1093
Antibodies or immunoglobulins; Fragments thereof , the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised…

Abstract

The presently disclosed subject matter provides antibodies or antigen-binding fragments thereof that bind to DLL3 and methods of using such antibodies or antigen-binding fragments thereof same.