Transforming growth factor beta receptor 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 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 the amino acid sequence of SEQ ID NO: 13,
wherein the fusion polypeptide does not include the amino acids corresponding to amino acids 1-22 and 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 of claim 1 , wherein the heterologous amino acid sequence is joined to the TβRII polypeptide by a linker, and wherein the heterologous amino acid sequence comprises a polypeptide portion selected from: an immunoglobulin Fc domain and a serum albumin.
3. The TβRII fusion polypeptide of claim 1 , wherein the first amino acid sequence consists of the amino acid sequence of SEQ ID NO: 13.
4. The TβRII fusion polypeptide of claim 1 , wherein the heterologous amino acid sequence comprises the amino acid sequence of SEQ ID NO: 21.
5. The TβRII fusion polypeptide of claim 3 , wherein the heterologous amino acid sequence comprises the amino acid sequence of SEQ ID NO: 21.
6. The TβRII fusion polypeptide of claim 5 , wherein the heterologous amino acid sequence is joined to the TβRII polypeptide by a linker.
7. The TβRII fusion polypeptide of claim 1 , wherein the fusion polypeptide binds Transforming Growth Factor β1 and Transforming Growth Factor β3.
8. The TβRII fusion polypeptide of claim 6 , wherein the fusion polypeptide binds Transforming Growth Factor β1 and Transforming Growth Factor β3.
9. A pharmaceutical preparation comprising the polypeptide of claim 1 and a pharmaceutically acceptable excipient.