MULTISPECIFIC ANTAGONISTS
Multispecific antagonists for targeting angiogenesis pathways are disclosed. The multispecific antagonists may be used for the treatment of disorders associated with angiogenesis pathways.
1 . A bispecific antagonist, comprising:
(1) an immunoglobulin scaffold comprising a CH3 domain;
(2) a first targeting domain comprising one or more VEGF or VEGFR binding domains; and
(3) a second targeting domain comprising one or more Tie2 receptor or Ang binding domains.
2 . The bispecific antagonist of claim 1 , wherein the second targeting domain is inserted into a loop region of the CH3 domain.
3 . The bispecific antagonist of claim 1 , wherein the second targeting domain is linked to a N-terminal or a C-terminal of the immunoglobulin scaffold.
4 . The bispecific antagonist of claim 1 , wherein the second targeting domain comprises a single copy or two copies of SEQ ID NO:6.
5 . The bispecific antagonist of claim 1 , wherein the first targeting domain comprises SEQ ID NO:1.
6 . The bispecific antagonist of claim 1 , wherein the first targeting domain comprises SEQ ID NO:88 and SEQ ID NO:89.
7 . The bispecific antagonist of claim 1 , wherein the first targeting domain comprises SEQ ID NO:1 and is attached to a C-terminal of the immunoglobulin scaffold, and wherein the second targeting domain comprises SEQ ID NO:7 and is inserted into a loop region of the CH3 domain of the immunoglobulin scaffold.
8 . The bispecific antagonist of claim 1 , wherein the first targeting domain comprises SEQ ID NO:1 and is attached to a N-terminal of the immunoglobulin scaffold, and wherein the second targeting domain comprises SEQ ID NO:7 and is linked to a C-terminal of the immunoglobulin scaffold.
9 . A pharmaceutical composition, comprising
the bispecific antagonist of claim 1 ; and
a pharmaceutically acceptable carrier.
10 . A method for treating a condition in a subject, comprising:
administering to the subject an effective amount of the pharmaceutical composition of claim 9 ,
wherein the condition is wet AMD or cancer.
11 . A trispecific antagonist, comprising:
(1) an immunoglobulin scaffold comprising a CH3 domain;
(2) a first targeting domain comprising one or more VEGF or VEGFR binding domains;
(3) a second targeting domain comprising one or more Tie2 receptor or Ang binding domains; and
(4) a third targeting domain comprising one or more PD-1 binding domains.
12 . The trispecific antagonist of claim 11 , wherein the second targeting domain is inserted into a loop region of the CH3 domain.
13 . The trispecific antagonist of claim 11 , wherein the second targeting domain comprises SEQ ID NO:2.
14 . The bispecific antagonist of claim 11 , wherein the second targeting domain comprises a single copy or two copies of SEQ ID NO:6.
15 . The trispecific antagonist of claim 11 , wherein the first targeting domain comprises SEQ ID NO:88 and SEQ ID NO:89.
16 . The trispecific antagonist of claim 11 , wherein the third targeting domain comprises SEQ ID NO:90 and SEQ ID NO:91.
17 . The trispecific antagonist of claim 11 , wherein the first targeting domain comprises SEQ ID NO:88 and SEQ ID NO:89 and is attached to a C-terminal of the immunoglobulin scaffold, wherein the second targeting domain comprises SEQ ID NO:2 and is inserted into a loop region of the CH3 domain of the immunoglobulin scaffold, and wherein the third targeting domain comprises SEQ ID NO:90 and SEQ ID NO:91 and is attached to a N-terminal of the immunoglobulin scaffold.
18 . The trispecific antagonist of claim 11 , wherein the first targeting domain comprises SEQ ID NO:88 and SEQ ID NO:89 and is attached to a C-terminal of the immunoglobulin scaffold, wherein the second targeting domain comprises SEQ ID NO:7 and is inserted into a loop region of the CH3 domain of the immunoglobulin scaffold, and wherein the third targeting domain comprises SEQ ID NO:90 and SEQ ID NO:91 and is attached to a N-terminal of the immunoglobulin scaffold.
19 . A pharmaceutical composition, comprising
the bispecific antagonist of claim 11 ; and
a pharmaceutically acceptable carrier.
20 . A method for treating a condition in a subject, comprising:
administering to the subject an effective amount of the pharmaceutical composition of claim 19 ,
wherein the condition is wet AMD or cancer.