Method of inhibiting HIV-1 binding to genital epithelia using V3 loop-specific peptides and GP340-specific antibodies

Patent metadata

Field	Value
Publication number	US-9580473-B2
Application number	US-30398507-A
Country	US
Kind code	B2
Filing date	Jun 8, 2007
Priority date	Jun 9, 2006
Publication date	Feb 28, 2017
Grant date	Feb 28, 2017

Abstract

This invention relates to methods compositions and devices for inhibiting infection of a subject's host cell by HIV. Specifically, the invention relates to methods and compositions capable of inhibiting the binding and subsequent infection by HIV of a host cell through the inhibition of the interaction between gp-340 expressed on the cell surface and V3 loop on the HIV envelope and devices comprising these compositions.

First claim

What is claimed is:

1. A method of inhibiting binding of a human immunodeficiency virus (HIV) to a genital tract tissue in a subject, comprising the step of: contacting the genital tract with an effective amount of an agent capable of inhibiting the binding between immunodeficiency virus and gp-340, wherein said agent inhibits binding of gp-120 with gp-340 and is selected from the group consisting of a V3 loop-specific peptide and an antibody or functional fragment thereof, wherein the antibody is a monoclonal antibody (mAb), a polyclonal antibody (pAb), or a humanized antibody specific against gp-340, wherein the V3 loop-specific peptide comprises a contiguous gp-120 V3 loop sequence at least 15 amino acid long, and wherein the antibody against gp-340 is specific for a Lewis Y (Le Y ) epitope.

2. The method of claim 1 , wherein the V3 loop-specific peptide comprises the amino acid sequence set forth in SEQ ID NO. 1, SEQ ID NO. 2 or a combination thereof.

3. The method of claim 1 , wherein said fragment is Fc, Fab, F(ab′)2, scFv or a combination thereof.

4. The method of claim 1 , further comprising the step of administering to the subject an effective amount of a soluble gp-340, gp-340 mimetic or a combination thereof.

5. The method of claim 1 , further comprising the step of administering to the subject an effective amount of 2,5-dimethoxy-substituted 5-bromopyridyl thiourea (PHI-236), nonoxynol-9 or a combination thereof.

6. A method of inhibiting attachment of a human immunodeficiency virus (HIV) to a host cell, comprising the step of contacting a gp340 protein expressed on the host cell with an agent capable of inhibiting attachment, wherein said agent inhibits binding of gp-120 with gp-340 and is a V3 loop-specific peptide or a gp340-specific antibody or a functional fragment thereof, wherein said antibody is a monoclonal antibody (mAb), a polyclonal antibody (pAb), or a humanized antibody, wherein the V3 loop-specific peptide comprises a contiguous gp-120 V3 loop sequence at least 15 amino acid long, and wherein the antibody against gp-340 is specific for a Lewis Y (Le Y ) epitope.

7. The method of claim 6 , wherein said fragment is Fc, Fab, F(ab′)2, scFv or a combination thereof.

8. The method of claim 6 , wherein the host cell is a vaginal, an endocervical or an ectocervical primary epithelial cell.

9. The method of claim 6 , wherein the V3 loop-specific peptide comprises the amino acid sequence set forth in SEQ ID NO. 1, SEQ ID NO. 2 or their combination.

10. The method of claim 6 , further comprising contacting the virus with 2,5-dimethoxy-substituted 5-bromopyridyl thiourea (PHI-236), nonoxynol-9, or a combination thereof.

Assignees

• Weissman Drew
• Stoddard Earl
• Univ Pennsylvania

Inventors

• Weissman Drew
• Stoddard Earl

Classifications

• C07K14/005 Primary

  from viruses · CPC title

• C07K14/47

  from mammals · CPC title

• A61K38/00

  Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) · CPC title

• C12N2740/16122

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

• C12N2740/16111

  concerning HIV env · CPC title