Antibody toxin conjugates
View Patent ↗The present invention provides conjugates formed between toxins and sugars and toxins and peptides, such as antibodies. In an exemplary embodiment, a toxin-sugar construct is conjugated to an antibody through an intact glycosyl linking group.
1. A compound having the formula:
wherein
X 1 , X 2 , X 3 , and X 4 are linking groups and are members selected from the group consisting of O, S, NH, (CH 2 ) q —NH, NH—(CH 2 ) q , NH—C(O)—O, O—C(O)—NH, (CH 2 ) q —NH—C(O)—O, O—C(O)—NH—(CH 2 ) q , C(O)—O, O—C(O), (CH 2 ) q —NH—C(O), C(O)—NH—(CH 2 ) q , NH—C(S), and C(S)—NH;
Ab is an antibody that binds to at least one antigen selected from the group consisting of respiratory syncytial virus (RSV), interleukin-2 (IL-2) receptor, carcinoembryonic antigen (CEA), platelet IIb/IIIa receptor, epidermal growth factor (EGF), HER-2 receptor, CD56, epidermal growth factor receptor (EGFR), CD33, CD22, and OBA1 antigens;
G is an intact glycosyl linking group covalently joining Ab to X 1 ;
T is a toxin;
A is an amplifier moiety;
Z is a bond cleaved by a metabolic/physiological process;
n is an integer from 1 to 1,000;
a is an integer from 1 to 10;
b is an integer from 1 to 10; and
q is and integer from 0 to 20.
2. A compound having the formula:
wherein
at least one of R 1 , R 2 , R 3 , R 4 , R 5 , is:
wherein
Ab is an antibody that binds to at least one antigen selected from the group consisting of RSV respiratory syncytial virus (RSV), interleukin-2 (IL-2) receptor, carcinoembryonic antigen (CEA), platelet IIb/IIIa receptor, epidermal growth factor (EGF), HER-2 receptor, CD56, epidermal growth factor receptor (EGFR), CD33, CD22, and OBA1 antigens;
G is an intact glycosyl linking group covalently joining Ab to Z 1 ;
T is a toxin;
r is an integer from 1 to 2,500;
A is an amplifier moiety;
Z 1 is selected from the group consisting of O, S, and NH;
Z 2 is selected from the group consisting of NH, and NH—(CH 2 ) q ;
and
X 1 , X 2 and X 3 are linking groups and are members selected from the group consisting of O, S, NH, (CH 2 ) q —NH, NH—(CH 2 ) q , NH—C(O)—O, O—C(O)—NH, (CH 2 ) q —NH—C(O)—O, O—C(O)—NH—(CH 2 ) q , C(O)—O, O—C(O), (CH 2 ) q —NH—C(O), C(O)—NH—(CH 2 ) q , NH—C(S), and C(S)—NH
wherein
n is an integer from 1 to 1,000; and
q is an integer from 0 to 20.
3. A compound having the formula:
wherein
X 1 , X 2 and X 4 are linking groups and are members selected from the group consisting of O, S, NH, (CH 2 ) q —NH, NH—(CH 2 ) q , NH—C(O)—O, O—C(O)—NH, (CH 2 ) q —NH—C(O)—O, O—C(O)—NH—(CH 2 ) q , C(O)—O, O—C(O), (CH 2 ) q —NH—C(O), C(O)—NH—(CH 2 ) q , NH—C(S), and C(S)—NH;
Ab is an antibody that binds to at least one antigen selected from the group consisting of respiratory syncytial virus (RSV), interleukin-2 (IL-2) receptor, carcinoembryonic antigen (CEA), platelet IIb/IIIa receptor, epidermal growth factor (EGF), HER-2 receptor, CD56, epidermal growth factor receptor (EGFR), CD33, CD22, and OBA1 antigens;
G is an intact glycosyl linking group covalently joining Ab to X 1 ;
T is a toxin;
A is an amplifier moiety;
n is an integer from 1 to 1,000; and
q is an integer from 0 to 20.
4. The compound according to claim 3 , having the formula:
wherein
n is an integer from 1 to 1,000.