Cross-linked antibodies
The present invention provides a compound consisting essentially of the following elements: one or more reactive groups; and two or more cross-linked antibodies or fragments thereof; characterised in that the or each reactive group is suitable for attaching an effector molecule but does not react with any of the antibodies or fragments thereof.
1. A compound of formula (I):
wherein:
A, A 1 and A 2 independently represent an antibody or fragment thereof;
L, L 1 and L 2 independently represent a spacer group;
R represents a reactive group which is suitable for attaching an effector molecule but does not react with any of A, A 1 and A 2 , and wherein R is selected from
except that when Y represents a covalent bond and B represents —NHCO— or —CO— then R is selected from
Y represents a covalent bond or —(CH 2 ) y -;
B represents —CONH—, —NHCO— or —CO—;
V represents a covalent bond or —(CH 2 ) v -;
W, W 1 and W 2 independently represent —(CH 2 ) w O—;
T, T 1 and T 2 independently represent a linker group;
v is 1, 2, 3 or 4;
w is 1, 2, 3 or 4; and
y is 1, 2, 3, 4, 5 or 6.
2. The compound according to claim 1 wherein A, A 1 and A 2 are each an Fab′ fragment.
3. The compound according to claim 1 wherein L, L 1 and L 2 are succinimide.
4. The compound according to claim 1 wherein T, T 1 and T 2 are independently selected from —(CH 2 ) t -, —(CH 2 ) t NHCO(CH 2 ) n -, —(CH 2 ) t NHCO(CH 2 ) x NHCO(CH 2 ) n -, —(CH 2 ) t NHCO(CH 2 ) p (OCH 2 CH 2 ) z NHCO(CH 2 ) n -, —(CH 2 ) r NHCO(CH 2 ) m -,
wherein:
t is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;
n is 1, 2, 3, 4, 5 or 6;
x is 2, 3, 4, 5 or 6;
z is 1 to 500;
p is 1, 2, 3, 4, 5 or 6;
m is 1, 2, 3, 4, 5, or 6; and
r is 2, 3, 4 or 5.