Broadly neutralizing human immunodeficiency virus type 1 (hiv-1) gp120-specific monoclonal antibody

Patent metadata

Field	Value
Publication number	US-2016264649-A1
Application number	US-201615152630-A
Country	US
Kind code	A1
Filing date	May 12, 2016
Priority date	Aug 31, 2010
Publication date	Sep 15, 2016
Grant date	—

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

What is claimed is:

1 . An isolated or non-naturally occurring PGT-121 monoclonal antibody 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: 143, 144 and 145.

2 . An isolated or non-naturally occurring PGT-121 monoclonal antibody 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 . One or more vectors containing and expressing a nucleic acid encoding the PGT-121 monoclonal antibody of claim 1 or 2 .

4 . The one or more vectors of claim 3 , wherein one vector encodes the light chain sequence and another vector encodes the heavy chain sequence.

5 . The one or more vectors of claim 3 , wherein one vector encodes the light chain sequence and the heavy chain sequence.

6 . The one or more vectors of claim 3 , wherein the vector is an adeno-associated virus vector.

7 . A cell containing and expressing the one or more vectors of claim 3 .

8 . A composition comprising the antibody of claim 1 or 2 .

9 . An immortalized B cell clone expressing the antibody of claim 1 or 2 .

10 . A pharmaceutical composition comprising the antibody 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
• Marcel Simek-Lemos Melissa Danielle De Jean De St

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

• A61K39/21

  Retroviridae, e.g. equine infectious anemia virus · CPC title

• C07K2317/565

  Complementarity determining region [CDR] · CPC title

• C07K2317/76

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