# US RE49,037 E1 · Broadly neutralizing antibody and uses thereof

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- Number: US RE49,037 E1
- Document ID: USRE49037E1
- Status: Granted
- Kind: E1
- Application number: 16/726,453
- Filed: 2019-12-24
- Granted: 2022-04-19
- Earliest claimed: 2014-06-11
- Assignees: International AIDS Vaccine Initiative; The Scripps Research Institute; Cornell University
- Applicants: International AIDS Vaccine Initiative; The Scripps Research Institute; Cornell University
- Inventors: Dennis R. Burton; Marit J. Van Gils; Wayne Koff; Pascal R. G. Poignard; Rogier W. Sanders; Melissa D. J. S. Simek-Lemos; Devin Sok
- Web page: https://patentgrep.com/patent/USRE49037E1

## CPC

- C07K 16/1063
- C07K 2317/21: from primates, e.g. man
- C07K 2317/55: Fab or Fab'
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)

## Abstract

The present invention relates to an exceptionally broad and potent neutralizing antibody which may comprise cross-clade neutralizing coverage of 83% at a median IC50 of 0.003 μg/ml, compositions containing the same and uses thereof.

## Claims

### Claim 1

A non-naturally occurring anti-HIV-1 monoclonal antibody or antigen binding portion thereof, comprising (a) a heavy chain sequence comprising an amino acid sequence encoded by SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, or SEQ ID NO: 13 and (b) a light chain sequence comprising an amino acid sequence encoded by SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, or SEQ ID NO: 26.

### Claim 2 (depends on 1)

The non-naturally occurring anti-HIV-1 monoclonal antibody or antigen binding portion of claim 1, wherein the heavy chain sequence is encoded by SEQ ID NO: 1 and the light chain sequence is encoded by SEQ ID NO: 14.

### Claim 3 (depends on 1)

A composition comprising the antibody or antigen binding portion of claim 1.

### Claim 4 (depends on 1)

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

### Claim 5 (depends on 1)

The antibody or antigen binding portion of claim 1, wherein the heavy chain sequence comprises a third complementarity determining region (CDRE3) of 33 to 34 amino acid residues.

### Claim 6 (depends on 5)

The antibody or antigen binding portion of claim 5, wherein a triad of aspartic acid residues at the tip of CDRH3 provides an anionic potential to the CDRH3.

### Claim 7

A non-naturally occurring anti-HIV-1 monoclonal antibody or antigen binding portion thereof, comprising
(a) the heavy chain CDRs of a heavy chain sequence encoded by SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, or SEQ ID NO: 13, and
(b) the light chain CDRs of a light chain sequence encoded by SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, or SEQ ID NO: 26.

### Claim 8 (depends on 7)

The antibody or antigen binding portion of claim 7 comprising the heavy chain CDR3 of any one of SEQ ID NO: 40-52 and the light chain CDR3 of any one of SEQ ID NO: 58-70.

### Claim 9 (depends on 7)

The antibody or antigen binding portion of claim 7, wherein the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 40, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 58.

### Claim 10 (depends on 8)

The antibody or antigen binding portion of claim 8, wherein a triad of aspartic acid residues at the tip of heavy chain CDR3 provides an anionic potential to the heavy chain CDR3.

### Claim 11

A non-naturally occurring anti-HIV-1 monoclonal antibody or antigen binding portion thereof comprising
(a) a heavy chain variable region comprising an amino acid sequence with at least 90% identity to the amino acid sequence encoded by SEQ ID NO:1, and
(b) a light chain variable region comprising an amino acid sequence with at least 90% identity to the amino acid sequence encoded by SEQ ID NO: 14.

### Claim 12 (depends on 11)

The antibody or antigen binding portion of claim 11, wherein the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 40, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 58.

### Claim 13 (depends on 11)

The antibody or antigen binding portion of claim 11, wherein the heavy chain variable region comprises an amino acid sequence with at least 95% identity to the amino acid sequence encoded by SEQ ID NO: 1, and the light chain variable region comprises an amino acid sequence with at least 95% identity to the amino acid sequence encoded by SEQ ID NO: 14.

### Claim 14

A non-naturally occurring anti-HIV-1 monoclonal antibody or antigen binding portion thereof comprising
(a) a heavy chain variable region comprising an amino acid sequence with at least 90% identity to the amino acid sequence encoded by SEQ ID NO:1, and
(b) a light chain variable region comprising an amino acid sequence with at least 90% identity to the amino acid sequence encoded by SEQ ID NO: 14,
wherein the antibody interacts with HIV gp120 V1/V2 domain of BG505.

### Claim 15 (depends on 14)

The antibody or antigen binding portion of claim 14, wherein the heavy chain variable region comprises an amino acid sequence with at least 95% identity to the amino acid sequence encoded by SEQ ID NO: 1, and the light chain variable region comprises an amino acid sequence with at least 95% identity to the amino acid sequence encoded by SEQ ID NO: 14.

### Claim 16 (depends on 14)

The antibody or antigen binding portion of claim 14, wherein the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 40, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 58.

### Claim 17

A non-naturally occurring anti-HIV-1 monoclonal antibody or antigen binding portion thereof comprising
(a) a heavy chain variable region comprising an amino acid sequence with at least 90% identity to the amino acid sequence encoded by SEQ ID NO:1, and
(b) a light chain variable region comprising an amino acid sequence with at least 90% identity to the amino acid sequence encoded by SEQ ID NO: 14,
wherein the antibody has a minimal cross-clade neutralization coverage of 80% on the 106-virus panel shown in FIG. 9.

### Claim 18 (depends on 17)

The antibody or antigen binding portion of claim 17, wherein the heavy chain variable region comprises an amino acid sequence with at least 95% identity to the amino acid sequence encoded by SEQ ID NO: 1, and the light chain variable region comprises an amino acid sequence with at least 95% identity to the amino acid sequence encoded by SEQ ID NO: 14.

### Claim 19 (depends on 17)

The antibody or antigen binding portion of claim 17, wherein the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 40, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 58.

### Claim 20

A non-naturally occurring anti-HIV-1 monoclonal antibody or antigen binding portion thereof comprising
(a) a heavy chain variable region comprising an amino acid sequence with at least 90% identity to the amino acid sequence encoded by SEQ ID NO: 1, wherein the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 40, and
(b) a light chain variable region comprising an amino acid sequence with at least 90% identity to the amino acid sequence encoded by SEQ ID NO: 14, wherein the light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 58,
wherein the antibody interacts with HIV gp120 V1/V2 domain of BG505, and has a minimal cross-clade neutralization coverage of 80% on the 106-virus panel shown in FIG. 9, and
wherein a triad of aspartic acid residues at the tip of the heavy chain CDR3 provides an anionic potential to the heavy chain CDR3.

### Claim 21 (depends on 7)

A pharmaceutical composition comprising the antibody or antigen binding portion of claim 7 and a pharmaceutically acceptable carrier.

### Claim 22 (depends on 11)

A pharmaceutical composition comprising the antibody or antigen binding portion of claim 11 and a pharmaceutically acceptable carrier.

### Claim 23

An isolated polypeptide comprising the amino acid sequence of any one of SEQ ID NO: 40-52.
