# US 2019/0169273 A1 · Monoclonal antibodies directed against trimeric forms of the hiv-1 envelope glycoprotein with broad and potent neutralizing activity

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- Number: US 2019/0169273 A1
- Document ID: US20190169273A1
- Status: Published application
- Kind: A1
- Application number: 16/275,936
- Filed: 2019-02-14
- Published: 2019-06-06
- Earliest claimed: 2009-03-17
- Assignees: Theraclone Sciences, Inc.; International AIDS Vaccine Initiative; The Scripps Research Institute
- Applicants: Theraclone Sciences, Inc.; International AIDS Vaccine Initiative; The Scripps Research Institute
- Inventors: Po-Ying Chan-Hui; Steven Frey; Ole Olsen; Jennifer Mitcham; Matthew Moyle; Sanjay K. Phogat; Dennis R. Burton; Laura Marjorie Walker; Pascal Raymond Georges Poignard; Wayne Koff; Melissa Danielle De Jean De St. Marcel Simek-Lemos; Stephen Kaminsky
- Web page: https://patentgrep.com/patent/US20190169273A1

## CPC

- C07K 16/114: Lentivirus (G), e.g. human immunodeficiency virus [HIV], feline immunodeficiency virus [FIV] or simian immunodeficiency virus [SIV]
- A61K 39/21: Retroviridae, e.g. equine infectious anemia virus
- A61P 31/14: for RNA viruses
- C07K 16/1145: {Env proteins, e.g. gp41, gp110/120, gp160, V3, principal neutralising domain [PND] or CD4-binding site}
- A61K 2039/505: {comprising antibodies}
- C07K 2317/33: Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
- C07K 2317/56: variable (Fv) region, i.e. VH and/or VL
- 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)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## 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 are 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.

## Claims

### Claim 1

An isolated and non-naturally occurring polynucleotide encoding (a) a light chain variable region comprising three complementarity determining regions comprising the amino acid sequences of SEQ ID NOS: 126, 127 and 45 and (b) a heavy chain variable region comprising three complementarity determining regions comprising the amino acid sequences of SEQ ID NOS: 123, 124 and 7.

### Claim 2

An isolated and non-naturally occurring polynucleotide encoding (a) a light chain variable region comprising three complementarity determining regions comprising the amino acid sequences of SEQ ID NOS: 97, 95 and 41 and (b) a heavy chain variable region comprising three complementarity determining regions comprising the amino acid sequences of SEQ ID NOS: 88, 89 and 6.

### Claim 3

An isolated and non-naturally occurring polynucleotide encoding (a) a light chain variable region comprising the amino acid sequence of SEQ ID NO: 30 and (b) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 28.

### Claim 4

An isolated and non-naturally occurring polynucleotide comprising (a) a light chain variable region comprising the nucleotide sequence of SEQ ID NO: 125 and (b) a heavy chain variable region comprising the nucleotide sequence of SEQ ID NO: 122.

### Claim 5

An isolated and non-naturally occurring polynucleotide encoding (a) a light chain variable region comprising the amino acid sequence of SEQ ID NO: 14 and (b) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 12.

### Claim 6

An isolated and non-naturally occurring polynucleotide comprising (a) a light chain variable region comprising the nucleotide sequence of SEQ ID NO: 100 and (b) a heavy chain variable region comprising the nucleotide sequence of SEQ ID NO: 99.

### Claim 7 (depends on 1, 2, 3, 4, 5, 6)

The polynucleotide of any one of claims 1-6, wherein the polynucleotide is a single-stranded DNA, a double-stranded DNA or an RNA molecule.

### Claim 8 (depends on 7)

The polynucleotide of claim 7, wherein the single-stranded DNA is a coding or antisense DNA, the double-stranded DNA is a genomic, cDNA or synthetic DNA and the RNA molecule is an hnRNA or a mRNA.

### Claim 9 (depends on 1, 2, 3, 4, 5, 6)

One or more vectors encoding the nucleic acid sequence of any one of claims 1-6.

### Claim 10 (depends on 9)

The one or more vectors of claim 9, wherein one vector encodes the light chain sequence and another vector encodes the heavy chain sequence.

### Claim 11 (depends on 9)

The one or more vectors of claim 9, wherein one vector encodes the light chain sequence and a heavy chain sequence.

### Claim 12 (depends on 9)

The one or more vectors of claim 9, wherein the vector is viral vector, a plasmid vector, a plant expression vector or a yeast expression vector.

### Claim 13 (depends on 12)

The one or more vectors of claim 12, wherein the viral vector is an adeno-associated virus vector.

### Claim 14 (depends on 9)

A cell containing and expressing the one or more vectors of claim 9.

### Claim 15 (depends on 14)

The cell of claim 14, wherein the cell is a prokaryotic host cell or a eukaryotic host cell.

### Claim 16 (depends on 15)

The cell of claim 15, wherein the prokaryotic host cell is Escherichia coli, the eucaryotic host cell is a yeast cell, an animal cell or a plant cell.

### Claim 17 (depends on 16)

The eucaryotic host cell of claim 16, wherein the yeast cell is Saccharomyces cerevisiae, Schizosaccharomyces pombe, or Pichia pastoris, the animal cell is a mammalian cell, or hybridoma cell and the plant cell is a tobacco, a corn cell, a soybean cell, or a rice cell.

### Claim 18 (depends on 17)

The eucaryotic host cell of claim 17, wherein the mammalian cell is a CHO cell, a COS cell, a HEK293T cell, a PER.C6 cell, a myeloma cell or a hybridoma cell.

### Claim 19 (depends on 1, 2, 3, 4, 5, 6)

A pharmaceutical composition comprising the polynucleotide of any one of claims 1-6 and a pharmaceutically acceptable excipient.

### Claim 20 (depends on 19)

A method of inhibiting HIV in a host comprising administering to the host a pharmaceutical composition of claim 19 under conditions whereby the polynucleotide or the vector expresses the antibody.