HIV-1 gp120 CD4 binding site antibodies targeting HIV escape mutants

Patent metadata

Field	Value
Publication number	US-12173052-B2
Application number	US-202117500171-A
Country	US
Kind code	B2
Filing date	Oct 13, 2021
Priority date	Jun 21, 2012
Publication date	Dec 24, 2024
Grant date	Dec 24, 2024

Abstract

Embodiments of the present invention are directed to compositions and methods for anti-HIV (anti-CD4 binding site) broadly neutralizing antibodies having improved potency and breadth for neutralizing a range of HIV strains. Combinations of broadly neutralizing antibodies can also improve potency over a single antibody composition.

First claim

What is claimed is:

1. A composition comprising:
an isolated anti-CD4 binding site (anti-CD4bs) VRC01-related % antibody variant having a heavy chain and a light chain comprising a heavy chain variable region and a light chain variable region,
the heavy chain variable region comprising:
a first substitution at position 54 of the heavy chain variable region having the amino acid sequence of SEQ ID NO: 85 according to Kabat numbering of, wherein the first substitution is selected from the group consisting of glycine, histidine, arginine, glutamine, asparagine, lysine, glutamic acid, and aspartic acid, and
a second substitution at position 47 of the heavy chain variable region having an amino acid sequence of SEQ ID NO: 85 according to Kabat numbering, wherein the second substitution is selected from valine, isoleucine, and threonine; and

the light chain variable region comprising:
a light chain substitution for serine at position 28 of the light chain variable region having the amino acid sequence of SEQ ID NO: 84 according to Kabat numbering.

2. The composition of claim 1 , wherein the first substitution is arginine.

3. The composition of claim 1 , wherein the anti-CD4bs VRC01-related % antibody variant is 45-46 m2.

4. A pharmaceutical composition comprising the composition of claim 1 or a fragment thereof, and a pharmaceutically acceptable carrier.

5. A method of preventing or treating an HIV infection or an HIV-related disease, the method comprising administering a therapeutically effective amount of the composition of claim 1 to a patient.

6. A method of preventing or treating an HIV infection or an HIV-related disease, the method comprising administering a therapeutically effective c7 amount of a combination of antibodies, the combination of antibodies comprising a first antibody and a second antibody, the first antibody comprising the composition of claim 1 and the second antibody comprising 10-1074 antibody or PG9 antibody.

Assignees

• Univ Rockefeller
• California Inst Of Techn

Inventors

• Diskin Ron
• West Anthony P
• Nussenzweig Michel
• Bjorkman Pamela J

Classifications

• C07K16/114

  Lentivirus (G), e.g. human immunodeficiency virus [HIV], feline immunodeficiency virus [FIV] or simian immunodeficiency virus [SIV] · CPC title

• C07K16/1145 Primary

  Env proteins, e.g. gp41, gp110/120, gp160, V3, principal neutralising domain [PND] or CD4-binding site · 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

• C07K2317/76

  Antagonist effect on antigen, e.g. neutralization or inhibition of binding · CPC title