TGFB type II-type III receptor fusions

Patent metadata

Field	Value
Publication number	US-9611306-B2
Application number	US-201314387901-A
Country	US
Kind code	B2
Filing date	Mar 28, 2013
Priority date	Mar 28, 2012
Publication date	Apr 4, 2017
Grant date	Apr 4, 2017

Abstract

Certain embodiments are directed to novel heterotrimeric fusions in which the ectodomain of the TGF-β type II receptor (TβP?II) is coupled to the N- and C-terminal ends of the endoglin-domain of the TGF-β type III receptor (TpRIIIE). Certain embodiments are directed to novel heterotrimeric polypeptides in which the ectodomain of the TGF-β type II receptor (TI3RII) is coupled to the N- and C-terminal ends of the endoglin-domain (E domain) of the TGF-β type III receptor (TI3RIII). This trimeric receptor, known as RER, can bind all three TGF-β isoforms with sub-nanomolar affinity and is effective at neutralizing signaling induced by all three TGF-β isoforms, but not other ligands of the TGF-β superfamily, such as activins, growth and differentiation factors (GDFs), and bone morphonogenetic proteins (BMPs).

First claim

The invention claimed is:

1. A TGFβ-binding heterotrimeric fusion protein wherein the fusion protein has an amino acid sequence that is 90% identical to SEQ ID NO: 2.

2. The fusion protein of claim 1 , further comprising an amino terminal signal sequence.

3. The fusion protein of claim 1 , further comprising an amino terminal or carboxy terminal tag.

4. The fusion protein of claim 3 , wherein the tag is a carboxy terminal hexa-histidine.

5. A method of treating a condition related to increased expression TGFβ comprising administering an effective amount of the fusion protein of claim 1 to subject in thereof.

6. The method of claim 5 , wherein the condition is a hyperproliferative disorder.

7. The method of claim 6 , wherein the hyperproliferative disorder is cancer.

8. The method of claim 5 , wherein the condition is fibrosis.

9. A heterotrimeric fusion protein wherein the fusion protein has the amino acid sequence of SEQ ID NO:2.

10. The fusion protein of claim 9 , further comprising an amino terminal signal sequence.

11. The fusion protein of claim 9 , further comprising an amino terminal or carboxy terminal tag.

12. The fusion protein of claim 11 , wherein the tag is a carboxy terminal hexa-Histidine.

Assignees

• Univ Texas

Inventors

• Hinck Andrew
• Sun Luzhe
• Zwieb Christian

Classifications

• C07K2319/32

  fusions with soluble part of a cell surface receptor, "decoy receptors" · CPC title

• C07K14/71 Primary

  for growth factors; for growth regulators · CPC title

• C07K14/495 Primary

  Transforming growth factor [TGF] · CPC title

• C12N15/64

  General methods for preparing the vector, for introducing it into the cell or for selecting the vector-containing host · CPC title