Engineered receptors for human cytomegalovirus and uses thereof

Patent metadata

Field	Value
Publication number	US-12570720-B2
Application number	US-202017761051-A
Country	US
Kind code	B2
Filing date	Sep 15, 2020
Priority date	Sep 17, 2019
Publication date	Mar 10, 2026
Grant date	Mar 10, 2026

Abstract

Modified platelet-derived growth factor receptor alpha (PDGFRα) polypeptides are described. The modified polypeptides include at least one amino acid substitution that allows the polypeptide to retain the capacity to bind a cytomegalovirus (CMV) trimer comprised of glycoprotein H (gH), gL and gO, but leads to reduced binding to one or more platelet-derived growth factor (PDGF) ligands. Use of the modified PDGFRα polypeptides for inhibiting CMV replication and/or spread, or treating a CMV infection, is also described.

First claim

The invention claimed is:

1 . A modified platelet-derived growth factor receptor alpha (PDGFRα) polypeptide, comprising a human PDGFRα or an extracellular fragment thereof, wherein the polypeptide comprises at least one amino acid substitution relative to wild-type human PDGFRαof SEQ ID NO: 1, and retains the capacity to bind a cytomegalovirus (CMV) trimer comprised of glycoprotein H (gH), gL and gO, but exhibits reduced binding to one or more platelet-derived growth factor (PDGF) ligands compared to wild type PDGFRα, wherein the single amino acid substitution is selected from the group consisting of L137K, L137Q, Y206S, V242K and V242T.

2 . The modified polypeptide of claim 1 , wherein the single amino acid substitution is selected from the group consisting of Y206S and V242K.

3 . An in vitro method of inhibiting CMV replication, comprising contacting the CMV with the modified polypeptide of claim 2 .

4 . A method of inhibiting CMV replication and/or spread in a subject, or a method of treating or inhibiting CMV infection in a subject, comprising administering to the subject a therapeutically effective amount of the modified polypeptide of claim 2 , thereby inhibiting CMV replication and/or spread in the subject, or treating or inhibiting CMV infection in the subject.

5 . The method of claim 4 , wherein the subject is (i) a female subject who is pregnant; (ii) an infant whose mother is positive for CMV; (iii) a subject with an immunodeficiency; (iv) a transplant recipient; or (v) a subject who is immunosuppressed.

6 . A composition comprising the modified polypeptide of claim 3 and a pharmaceutically acceptable carrier.

7 . The modified polypeptide of claim 1 , wherein the single amino acid substitution is V242K.

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

9 . The modified polypeptide of claim 1 , comprising full-length human PDGFRα.

10 . The modified polypeptide of claim 1 , wherein the polypeptide consists of an extracellular fragment of human PDGFRα.

11 . The modified polypeptide of claim 10 , wherein the extracellular fragment corresponds to residues 24 to 524 of human PDGFRα.

12 . A fusion protein comprising the modified polypeptide of claim 1 and a heterologous polypeptide.

13 . The fusion protein of claim 12 , wherein the heterologous polypeptide is an Fc protein, a fluorescent protein, an enzyme, an antibody or antigen-binding protein, a cytokine, a cellular ligand or receptor, or serum albumin.

14 . A composition comprising the modified polypeptide of claim 1 and a pharmaceutically acceptable carrier.

Assignees

• Univ Illinois

Inventors

• Procko Erik

Classifications

• C07K2319/30

  Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto · CPC title

• A61P31/20

  for DNA viruses · CPC title

• C07K2319/00

  Fusion polypeptide · CPC title

• C07K14/71 Primary

  for growth factors; for growth regulators · CPC title