Polypeptides targeting HIV fusion

Patent metadata

Field	Value
Publication number	US-10407490-B2
Application number	US-201615568830-A
Country	US
Kind code	B2
Filing date	Apr 14, 2016
Priority date	Apr 24, 2015
Publication date	Sep 10, 2019
Grant date	Sep 10, 2019

Abstract

The invention is directed to polypeptides comprising a CD4 binding moiety, a gp41 binding moiety, a HIV fusion peptide inhibitor moiety and combinations thereof. More specifically, the present invention relates to polypeptides comprising a fibronectin-based scaffold domain protein that binds CD4, a fibronectin-based scaffold domain protein that binds the N17 domain of gp41, and a HIV fusion peptide inhibitor or combinations thereof. The invention also relates to the use of the innovative proteins in therapeutic applications to treat HIV.

First claim

What is claimed is:

1. A polypeptide comprising three active domains, wherein domain one is a fibronectin-based scaffold domain protein that binds cluster of differentiation 4 (CD4) and comprises an amino acid sequence that is at least 90% identical to the amino acid sequence of any one of SEQ ID NOs: 95-114, domain two is a fibronectin-based scaffold domain protein that binds the N17 domain of glycoprotein 41 (gp41) and comprises an amino acid sequence that is at least 90% identical to the amino acid sequence of any one of SEQ ID NOs: 115-371, and domain three is a human immunodeficiency virus (HIV) fusion peptide inhibitor.

2. The polypeptide of claim 1 , wherein the polypeptide comprises an amino acid sequence that is at least 90% identical to the non-linker regions of SEQ ID NO: 9.

3. The polypeptide of claim 1 , wherein the polypeptide comprises an amino acid sequence that is 100% identical to the non-linker regions of SEQ ID NO: 10.

4. The polypeptide of claim 1 wherein the HIV fusion peptide inhibitor comprises an amino acid sequence that is at least 90% identical to the amino acid sequence of any one of SEQ ID NOs: 372-392.

5. A pharmaceutical composition comprising the polypeptide of claim 1 , and a pharmaceutically acceptable carrier.

6. A method of treating HIV in a subject in need thereof, comprising administering to the subject an effective amount of the peptide according to claim 1 or a pharmaceutical composition comprising the peptide according to claim 1 .

7. A polypeptide comprising the amino acid sequence of SEQ ID NO: 9.

8. A pharmaceutical composition comprising the polypeptide of claim 7 , and a pharmaceutically acceptable carrier.

9. A method of treating HIV in a subject in need thereof, comprising administering to the subject an effective amount of the peptide according to claim 7 or a pharmaceutical composition comprising the peptide according to claim 7 .

10. A polypeptide comprising the amino acid sequence of SEQ ID NO: 10.

11. A fibronectin-based scaffold domain protein that binds CD4, wherein the fibronectin-based scaffold domain protein comprises an amino acid sequence that is at least 90% identical to the amino acid sequence of any one of SEQ ID NOs: 95-114.

12. A fibronectin-based scaffold domain protein that binds the N17 domain of gp41, wherein the fibronectin-based scaffold domain protein comprises an amino acid sequence that is at least 90% identical to the amino acid sequence of any one of SEQ ID NOs: 115-371.

Assignees

• Bristol Myers Squibb Co
• Viiv Healthcare Uk No 5 Ltd

Inventors

• Krystal Mark R
• Wensel David L
• Davis Jonathan

Classifications

• C07K14/78 Primary

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

• C07K14/79

  Transferrins, e.g. lactoferrins, ovotransferrins · CPC title

• A61P31/18

  for HIV · CPC title

• C07K14/005 Primary

  from viruses · CPC title

• C07K2319/31

  fusions, other than Fc, for prolonged plasma life, e.g. albumin · CPC title