Broadly neutralizing human immunodeficiency virus type 1 (HIV-1) GP120-specific monoclonal antibody

Patent metadata

Field	Value
Publication number	US-10836811-B2
Application number	US-201715701679-A
Country	US
Kind code	B2
Filing date	Sep 12, 2017
Priority date	Aug 31, 2010
Publication date	Nov 17, 2020
Grant date	Nov 17, 2020

Abstract

The invention provides a method for obtaining a broadly neutralizing antibody (bNab), including screening memory B cell cultures from a donor PBMC sample for neutralization activity against a plurality of HIV-1 species, cloning a memory B cell that exhibits broad neutralization activity; and rescuing a monoclonal antibody from that memory B cell culture. The resultant monoclonal antibodies may be characterized by their ability to selectively bind epitopes from the Env proteins in native or monomeric form, as well as to inhibit infection of HIV-1 species from a plurality of clades. Compositions containing human monoclonal anti-HIV antibodies used for prophylaxis, diagnosis and treatment of HIV infection are provided. Methods for generating such antibodies by immunization using epitopes from conserved regions within the variable loops of gp120 are provided. Immunogens for generating anti-HIV1 bNAbs are also provided. Furthermore, methods for vaccination using suitable epitopes are provided.

First claim

The invention claimed is:

1. A non-naturally occurring PGT-121 monoclonal antibody or antigen binding portion thereof comprising (a) a light chain variable region comprising three complementarity determining regions comprising the amino acid sequences of SEQ ID NOS: 150, 151 and 152 and (b) a heavy chain variable region comprising three complementarity determining regions comprising the amino acid sequences of SEQ ID NOS: 143, 144 and 145.

2. A non-naturally occurring PGT-121 monoclonal antibody or antigen binding portion thereof comprising (a) a light chain variable region comprising three complementarity determining regions having the amino acid sequences of SEQ ID NOS: 150, 151 and 152 and (b) a heavy chain variable region comprising three complementarity determining regions having the amino acid sequences of SEQ ID NOS: 90, 265 and 143.

3. An immortalized B cell clone expressing the antibody or antigen binding portion thereof of claim 1 or 2 .

4. A pharmaceutical composition comprising the antibody or antigen binding portion thereof of claim 1 or 2 and a pharmaceutically acceptable carrier.

Assignees

• Theraclone Sciences Inc
• Scripps Research Inst
• Int Aids Vaccine Initiative

Inventors

• Chan-Hui Po-Ying
• Doores Katherine
• Huber Michael
• Kaminsky Stephen
• Frey Steven
• Olsen Ole
• Mitcham Jennifer
• Moyle Matthew
• Phogat Sanjay K
• Burton Dennis R
• Walker Laura Majorie
• Poignard Pascal Raymond Georges
• Koff Wayne
• Simek-Lemos Melissa Danielle De Jean De St Marcel

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

• C07K2317/565

  Complementarity determining region [CDR] · CPC title

• C07K2317/21

  from primates, e.g. man · CPC title

• C07K2317/92

  Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value · CPC title