Transforming growth factor-beta receptor type II fusion polypeptides
In certain aspects, the present disclosure relates to polypeptides comprising a truncated, ligand-binding portion of the extracellular domain of TβRII polypeptide useful to selectively antagonize a TβRII ligand. The disclosure further provides compositions and methods for use in treating or preventing TGFβ associated disorders.
1. A Transforming Growth Factor β Receptor II (TβRII) fusion polypeptide consisting of:
a) a first amino acid sequence from the extracellular domain of TβRII, wherein the first amino acid sequence consists of an amino acid sequence at least 95% identical to SEQ ID NO: 13, or active fragment thereof;
b) a heterologous portion; wherein the heterologous portion is an immunoglobulin Fc domain; and
c) a linker joining the first amino acid sequence to the immunoglobulin Fc domain;
wherein the fusion polypeptide does not include a signal sequence and does not include the amino acids corresponding to amino acids 185-592 of SEQ ID NO: 6;
and wherein the fusion polypeptide binds Transforming Growth Factor β1 or Transforming Growth Factor β3.
2. The TβRII fusion polypeptide according to claim 1 , wherein the first amino acid sequence consists of SEQ ID NO: 13.
3. The TβRII fusion polypeptide according to claim 2 , wherein the immunoglobulin Fc domain comprises the amino acid sequence of SEQ ID NO: 21.
4. The TβRII fusion polypeptide according to claim 1 , wherein the polypeptide is glycosylated.
5. The TβRII fusion polypeptide of claim 1 , wherein the polypeptide has a glycosylation pattern characteristic of expression of the polypeptide in CHO cells.
6. The TβRII fusion polypeptide according to claim 1 , wherein the immunoglobulin Fc domain comprises the amino acid sequence of SEQ ID NO: 21.
7. The TβRII fusion polypeptide of claim 1 , wherein the fusion polypeptide binds Transforming Growth Factor β1 and Transforming Growth Factor β3.
8. A homodimer comprising two polypeptides as defined in claim 1 .
9. A pharmaceutical preparation comprising the polypeptide of claim 1 , and a pharmaceutically acceptable excipient.
10. A pharmaceutical preparation comprising the homodimer of claim 8 , and a pharmaceutically acceptable excipient.
11. A Transforming Growth Factor β Receptor II (TβRII) fusion polypeptide comprising a first amino acid sequence from the extracellular domain of TβRII and a heterologous amino acid sequence, wherein the first amino acid sequence consists of an amino acid sequence at least 95% identical to SEQ ID NO: 13, or active fragment thereof; wherein the heterologous amino acid sequence comprises the amino acid sequence of any one of SEQ ID NOs: 19, 20 or 21; and wherein the fusion polypeptide does not include a signal sequence and does not include the amino acids corresponding to amino acids 185-592 of SEQ ID NO: 6; and wherein the fusion polypeptide binds Transforming Growth Factor (31 or Transforming Growth Factor β3.
12. The TβRII fusion polypeptide according to claim 11 , wherein the heterologous amino acid sequence is joined to the TβRII polypeptide by a linker.
13. The TβRII fusion polypeptide according to claim 11 , wherein the first amino acid sequence consists of SEQ ID NO: 13.
14. The TβRII fusion polypeptide according to claim 11 , wherein the polypeptide is glycosylated.
15. The TβRII fusion polypeptide of claim 11 , wherein the polypeptide has a glycosylation pattern characteristic of expression of the polypeptide in CHO cells.
16. The TβRII fusion polypeptide of claim 11 , wherein the fusion polypeptide binds Transforming Growth Factor β1 and Transforming Growth Factor β3.
17. A homodimer comprising two polypeptides as defined in claim 11 .
18. A pharmaceutical preparation comprising the polypeptide of claim 11 , and a pharmaceutically acceptable excipient.
19. A pharmaceutical preparation comprising the homodimer of claim 17 , and a pharmaceutically acceptable excipient.