Targeted therapeutic agents comprising multivalent protein-biopolymer fusions

Patent metadata

Field	Value
Publication number	US-2019345228-A1
Application number	US-201916525374-A
Country	US
Kind code	A1
Filing date	Jul 29, 2019
Priority date	Mar 26, 2015
Publication date	Nov 14, 2019
Grant date	—

Abstract

Provided herein are fusion proteins including at least one binding polypeptide and at least one unstructured polypeptide. The fusion protein may further include at least one linker. Further provided are methods for determining the presence of a target in a sample, methods of treating a disease, methods of diagnosing a disease in a subject, and methods of determining the effectiveness of a treatment for a disease in a subject. The methods may include administering to the subject an effective amount of the fusion protein.

First claim

We claim:

1 . A fusion protein comprising at least one binding polypeptide, a plurality of unstructured polypeptides, and a linker positioned between at least two adjacent unstructured polypeptides.

2 . The fusion protein of claim 1 , wherein the linker comprises at least one glycine and at least one serine.

3 . The fusion protein of claim 1 , wherein the linker comprises an amino acid sequence consisting of SEQ ID NO: 3 ((Gly 4 Ser) 3 ).

4 . The fusion protein of claim 1 , wherein the linker comprises an amino acid sequence consisting of SEQ ID NO: 4.

5 . The fusion protein of claim 1 , wherein the binding polypeptide binds a target, and wherein the fusion protein binds more than one target.

6 . The fusion protein of claim 1 , wherein the at least one binding polypeptide comprises a Fibronectin type III (FnIII) domain.

7 . The fusion protein of claim 6 , wherein the FnIII domain binds TNF-related apoptosis-inducing ligand receptor 2 (TRAILR-2).

8 . The fusion protein of claim 1 , wherein the at least one binding polypeptide comprises at least one amino acid sequence of consisting of SEQ ID NO: 17 (RGDS).

9 . The fusion protein of claim 1 , wherein at least one unstructured polypeptide comprises at least one PG motif comprising an amino acid sequence selected from PG, P(X) n G (SEQ ID NO: 18), and (U) m P(X) n G(Z) p (SEQ ID NO: 20), or a combination thereof, wherein m, n, and p are independently an integer from 1 to 15, and wherein U, X, and Z are independently any amino acid.

10 . The fusion protein of claim 1 , wherein at least one unstructured polypeptide comprises a thermally responsive polypeptide.

11 . The fusion protein of claim 10 , wherein the thermally responsive polypeptide comprises an elastin-like polypeptide (ELP).

12 . The fusion protein of claim 1 , wherein at least one unstructured polypeptide comprises an amino acid sequence consisting of (VPGXG) n (SEQ ID NO: 19), wherein X is any amino acid except proline and n is an integer greater than or equal to 1.

13 . The fusion protein of claim 12 , wherein n is 60, 120, or 180.

14 . The fusion protein of claim 12 , wherein X is valine.

15 . The fusion protein of claim 1 , further comprising at least one linker positioned between the at least one binding polypeptide and at least one unstructured polypeptide.

Assignees

• Univ Duke

Inventors

• Chilkoti Ashutosh
• Manzari Mandana
• Fevre Mareva

Classifications

• C07K14/78 Primary

  Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin or cold insoluble globulin [CIG] · CPC title

• C07K2319/74

  containing a fusion for binding to a cell surface receptor · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• C07K2319/00

  Fusion polypeptide · CPC title

• A61K9/0019

  Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00) · CPC title