IP Library › Granted Patent US 8,226,955
Granted Patent B2
US 8,226,955 · App. 12/859,356 · Granted Jul 24, 2012

Chimeric HIV Env proteins comprising CD4 mini-proteins or CD4 mimetics that are capable of inducing neutralizing antibody responses against cryptic Env epitopes

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Quick Facts
Patent No.
US 8,226,955
App. No.
12/859,356
Granted
Jul 24, 2012
Kind
B2
Abstract

Env-CD4 polypeptide complexes and hybrids that expose cryptic epitopes important in virus neutralization are disclosed. Method of diagnosis, treatment and prevention using the polypeptides are also provided.

Claims (18)

1. A hybrid Human Immunodeficiency Virus (HIV) Envelope (Env)-CD4 protein comprising:

(1) an HIV Env polypeptide which comprises a CD4-binding site and a deletion region from which one or more variable (V) regions are deleted; and

(2) a CD4 mini-protein or a CD4-mimetic inserted into the deletion region, wherein the CD4 mini-protein or CD4-mimetic maintains the structural conformation of a CDR2-like loop; and

wherein the insertion of the CD4 mini-protein or the CD4 mimetic leads to exposure of a cryptic HIV envelope epitope in or near the CD4-binding site or in or near the chemokine receptor-binding site.

2. The polypeptide of claim 1 , wherein the deletion region comprises a deletion in V1.

3. The polypeptide of claim 1 , wherein the deletion region comprises a deletion in V2.

4. The polypeptide of claim 1 , wherein the deletion region comprises a deletion in V1 and V2.

5. The polypeptide of claim 1 , further comprising one or more linker sequences.

6. The polypeptide of claim 1 wherein the one or more linker sequences flank the CD4 mini-protein or the CD4 mimetic.

7. The polypeptide of claim 1 , wherein the CD4 mini-protein is selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3 and SEQ ID NO:4.

8. The polypeptide of claim 1 wherein the CD4 mini-protein is inserted in the deletion region.

9. The polypeptide of claim 1 wherein the CD4 mimetic is inserted in the deletion region.

10. The polypeptide of claim 1 wherein the HIV Env polypeptide comprises gp140.

11. A composition comprising the polypeptide of claim 1 .

12. The composition of claim 11 , further comprising an adjuvant.

13. A method of inducing an immune response in a subject, comprising administering to the subject the composition of claim 11 .

14. The method of claim 13 wherein the subject is a mammal.

15. The method of claim 14 wherein the subject is a human.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 22, 2016
From: NOVARTIS VACCINES AND DIAGNOSTICS INC
To: GLAXOSMITHKLINE BIOLOGICALS SA
Reel/Frame 038980/0484 →