Antibody-IL-10 fusion proteins
The application relates to compositions or formulations comprising variant IL-10 molecules, fusion proteins, and chimeric proteins thereof useful for the treatment of cancer, inflammatory diseases or disorders, and autoimmune diseases or disorders.
1. A fusion protein of formula (I, IV, V, VI, or VII)
IL10-L 1 -X 1 -L 1 -X 2 -L 1 -IL10 (Formula I);
X 1 -L 2 -X 2 -L 1 -IL10 (Formula IV);
IL10-L 1 -X 1 -L 2 -X 2 (Formula V);
X 1 -L 1 -IL10 (Formula VI);
IL10-L 1 -X2 (Formula VII);
wherein
“IL-10” is a monomer sequence selected from SEQ ID No: 3, 14, or, 55;
“L 1 ” is a linker of SEQ ID No: 31 or 54;
“L 2 ” is a linker of SEQ ID No: 30;
“X 1 ” is a VH region obtained from a first antibody specific for epidermal growth factor receptor (EGFR), CD52, PD-L1, PD-1, TIM3, BTLA, LAG3 or CTLA4; CD20; CD47; GD-2; HER2; EpCAM; ICAM (ICAM-1, -2, -3, -4, -5), VCAM, FAPα; 5T4; Trop2; EDB-FN; TGFβ Trap; MAdCAM, β7 integrin subunit; α4β7 integrin; α4 integrin SR-A1; SR-A3; SR-A4; SR-A5; SR-A6; SR-B; dSR-C1; SR-D1; SR-E1; SR-F1; SR-F2; SR-G; SR-H1; SR-H2; SR-11; SR-J1; HIV, or Ebola;
“X 2 ” is a VL region obtained from the same antibody as X 1 .
2. The fusion protein according to claim 1 , wherein formula IV and V are capable of forming a fusion protein complex where the IL-10 monomer from each of formula IV and V are capable of forming a functional homodimeric IL-10 or variant thereof.
3. The fusion protein according to claim 2 , wherein formula IV is SEQ ID No: 50.
4. The fusion protein according to claim 2 , wherein formula V is SEQ ID No: 51.
5. The fusion protein according to claim 1 , wherein formula VI and VII are capable of forming a fusion protein complex where the IL-10 monomer from each of formula VI and VII are capable of forming a functional homodimeric IL-10 or variant thereof.
6. The fusion protein according to claim 1 , wherein formula I is SEQ ID No: 45.
7. The fusion protein according to claim 1 , wherein the VH region and the VL region are from an anti-Ebola antibody; and wherein the VH region and VL region comprise a framework region with 6 CDRs engrafted with 6 CDRs from a second antibody selected from EGFR; CD52; PD-L1; PD-1; TIM3; BTLA; LAG3; CTLA4; CD20; CD47; GD-2; HER2; EpCAM; ICAM-1; ICAM-2; ICAM-3; ICAM-4; ICAM-5; VCAM, FAPα; 5T4; Trop2; EDB-FN; TGFβ Trap; MAdCAM, β7 integrin subunit; α4β7 integrin; α4 integrin SR-A1; SR-A3; SR-A4; SR-A5; SR-A6; SR-B; dSR-C1; SR-D1; SR-E1; SR-F1; SR-F2; SR-G; SR-H1; SR-H2; SR-I1; or SR-J1.
8. The fusion protein according to claim 1 , wherein the VH region and the VL region comprise modifications that reduce the antigenicity in a subject.
9. A pharmaceutical composition comprising a therapeutically effective amount of the fusion protein according to claim 1 , and a pharmaceutically acceptable carrier, excipient, preservative, stabilizers, or any combination thereof.
10. The fusion protein according to claim 7 , wherein the VH region and the VL region comprise the framework regions from an anti-Ebola antibody.