Polypeptides targeting HIV fusion

Patent metadata

Field	Value
Publication number	US-11155602-B2
Application number	US-201916533941-A
Country	US
Kind code	B2
Filing date	Aug 7, 2019
Priority date	Apr 24, 2015
Publication date	Oct 26, 2021
Grant date	Oct 26, 2021

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

We claim:

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

2. The polypeptide of claim 1 , wherein the two domains are connected to each other in any order by linkers.

3. The polypeptide of claim 1 , further comprising one or more pharmacokinetic (PK) moieties selected from the group consisting of polyethylene glycol, sialic acid, Fc, Fc fragment, transferrin, serum albumin, a serum albumin binding protein, and a serum immunoglobulin binding protein.

4. The polypeptide of claim 3 , wherein the PK moiety is Fc.

5. The polypeptide of claim 4 , wherein the Fc is attached to the N-terminus of the polypeptide.

6. The polypeptide of claim 3 , wherein the PK moiety is human serum albumin.

7. The polypeptide of claim 6 , wherein the human serum albumin is attached to the N-terminus of the polypeptide.

Assignees

• Viiv Healthcare No 5 Ltd
• Viiv Healthcare Uk No 5 Ltd

Inventors

• Krystal Mark R
• Wensel David L
• Davis Jonathan

Classifications

• C12N2740/16122

  New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes · CPC title

• C07K2319/31

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

• C07K14/765

  Serum albumin, e.g. HSA · CPC title

• A61K47/60 Primary

  the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol · CPC title

• C07K14/005 Primary

  from viruses · CPC title