Albumin binding domain fusion proteins
Compositions that include an albumin binding domain and a fusion partner (e.g., a cytokine or a binding moiety) are provided. Such therapeutics have increased serum half-life and find use in applications where one or more such therapeutics are needed, for example, in oncology applications.
1. A composition comprising an albumin binding domain (ABD), said ABD comprising:
a) a variable heavy chain comprising a vhCDR1, a vhCDR2 and a vhCDR3 of a variable heavy chain having SEQ ID NO: 25; and
b) a variable light chain comprising a vlCDR1, a vlCDR2 and a vlCDR3 of a variable light chain having SEQ ID NO: 29.
2. The composition comprising an albumin binding domain according to claim 1 , wherein said vhCDR1 comprises SEQ ID NO: 26, said vhCDR2 comprises SEQ ID NO: 27, said vhCDR3 comprises SEQ ID NO: 28, said vlCDR1 comprises SEQ ID NO: 30, said vlCDR2 comprises SEQ ID NO: 31, and said vlCDR3 comprises SEQ ID NO: 32.
3. The composition according to claim 1 , wherein said variable heavy chain of said ABD comprises SEQ ID NO: 25, and said variable light chain of said ABD comprises SEQ ID NO: 29.
4. An albumin binding domain (ABD) fusion protein comprising an ABD attached to a fusion partner, wherein said ABD comprises a variable heavy chain comprising a vhCDR1, a vhCDR2 and a vhCDR3 of a variable heavy chain having SEQ ID NO: 25, and a variable light chain comprising a vlCDR1, a vlCDR2 and a vlCDR3 of variable light chain having SEQ ID NO: 29.
5. The ABD fusion protein according to claim 4 , wherein said vhCDR1 comprises SEQ ID NO: 26, said vhCDR2 comprises SEQ ID NO: 27, said vhCDR3 comprises SEQ ID NO: 28, said vlCDR1 comprises SEQ ID NO: 30, said vlCDR2 comprises SEQ ID NO: 31, and said vlCDR3 comprises SEQ ID NO: 32.
6. The ABD fusion protein according to claim 4 , wherein said variable heavy chain of said ABD comprises SEQ ID NO: 25 and said variable light chain of said ABD comprises SEQ ID NO: 29.
7. The ABD fusion protein according to claim 4 , wherein said fusion partner is a cytokine.
8. The ABD fusion protein according to claim 7 , wherein said cytokine is selected from the group consisting of: IL-2, IL-7, IL-12, IL-15, IL-18, IL-21, GM-CSF and IFN-α.
9. The ABD fusion protein according to claim 4 , wherein said fusion partner is an scFv comprising an scFv variable heavy chain and an scFv variable light chain.
10. The ABD fusion protein according to claim 9 , wherein said scFv is selected from the group consisting of an anti-TGFβ scFv, an anti-PD-L1 scFv, an anti-TNF scFv, an anti-IL-1 scFv, an anti-IL-6 scFv, an anti-IL-8 scFv, an anti-IL-17A scFv, an anti-IL-17B scFv, an anti-IL-17C scFv, an anti-IL-17D scFv, an anti-IL-17E scFv, an anti-IL-17F scFv, and an anti-IL-23 scFv.
11. An ABD fusion protein according to the formula: (FP1)-L1-(ABD)-L2-(FP2),
wherein ABD is an albumin binding domain comprising a variable heavy chain and a variable light chain;
wherein FP1 and FP2 are a first fusion partner and a second fusion partner, respectively;
wherein L1 and L2 are a first and second linker, respectively;
where said variable heavy chain of said ABD comprises a vhCDR1, a vhCDR2 and a vhCDR3 of a variable heavy chain having SEQ ID NO: 25; and
where said variable light chain of said ABD comprises a vlCDR1, a vlCDR2 and a vlCDR3 of a variable light chain having SEQ ID NO: 29.
12. The ABD fusion protein according to claim 11 , wherein said vhCDR1 comprises SEQ ID NO: 26, said vhCDR2 comprises SEQ ID NO: 27, said vhCDR3 comprises SEQ ID NO: 28, said vlCDR1 comprises SEQ ID NO: 30, said vlCDR2 comprises SEQ ID NO: 31, and said vlCDR3 comprises SEQ ID NO: 32.
13. The ABD fusion protein according to claim 11 , wherein said variable heavy chain of said ABD and said variable light chain comprises SEQ ID NO: 25 and said variable light chain of said ABD comprises SEQ ID NO: 29.
14. The ABD fusion protein according to claim 11 , wherein said FP1 and said FP2 are a first cytokine and a second cytokine respectively.
15. The ABD fusion protein according to claim 14 , wherein said first cytokine and said second cytokine are selected from the group consisting of:
IL-2 and IL-12; IL-7 and IL-15; IL-15 and IL-12; IL-18 and GM-CSF; IL-21 and IL-15; GM-CSF and IL-12; GM-CSF and IL-21; and IFN-α and IL-15.
16. The ABD fusion protein according to claim 11 , wherein said FP1 and said FP2 are a first scFv and a second scFv, respectively.
17. The ABD fusion protein according to claim 11 , wherein said FP1 and said FP2 are selected from the group consisting of a TNF scFv and an IL-1 scFv; a TNF scFv and an IL-6 scFv; a TNF scFv and an IL-8 scFv; a TNF scFv and an anti-IL-17A, anti-IL-17B, anti-IL-17C, anti-IL-17D, anti-IL-17E, or anti-IL-17F scFv; a TNF scFv and an IL-23 scFv; a first TNF scFv and a second TNF scFv; an anti-PD-L1 scFv and an IL-12; an anti-PD-L1 scFv and an IL-15; an anti-PD-L1 scFv and an anti-TGFβ scFv; a first anti-PD-L1 scFv and a second PD-L1 scFv; an anti-TGFβ scFv and an IL-12; an anti-TGFβ scFv and an IL-15; an anti-TGFβ scFv and a PD-L1 scFv; and a first anti-TGFβ scFv and a second anti-TGFβ scFv.