# US 11,078,283 B2 · Anti-PD-L1 antibodies and methods of use

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- Number: US 11,078,283 B2
- Document ID: US11078283B2
- Status: Granted
- Kind: B2
- Application number: 16/250,779
- Filed: 2019-01-17
- Published: 2019-07-18
- Granted: 2021-08-03
- Earliest claimed: 2018-01-17
- Assignees: Apexigen, Inc.
- Applicants: Apexigen, Inc.
- Inventors: Pia Björck; Christine Tan; Erin Filbert; Xiaodong Yang
- Web page: https://patentgrep.com/patent/US11078283B2

## CPC

- C07K 16/2827: {against B7 molecules, e.g. CD80, CD86}
- A61P 35/00: Antineoplastic agents
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- C07K 2317/31: multispecific
- C07K 2317/33: Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
- C07K 2317/52: Constant or Fc region; Isotype
- C07K 2317/522: CH1 domain
- C07K 2317/55: Fab or Fab'
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/75: Agonist effect on antigen
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

Provided are anti-programmed death-ligand 1 (PD-L1) monoclonal antibodies and related compositions, which may be used in any of a variety of therapeutic methods for the treatment of inflammatory and oncological diseases. Specifically, high affinity, humanized anti-PD-L1 antibodies are provided.

## Claims

### Claim 1

An isolated antibody, or an antigen-binding fragment thereof, that binds to PD-L1, comprising
(i) a heavy chain variable (VH) region comprising a VHCDR1 set forth in SEQ ID NO: 20, a VHCDR2 set forth in SEQ ID NO: 21, and a VHCDR3 set forth in SEQ ID NO: 22; and
(ii) a light chain variable (VL) region comprising a VLCDR1 set forth in SEQ ID NO: 23, a VLCDR2 set forth in SEQ ID NO: 24, and a VLCDR3 set forth in SEQ ID NO: 25.

### Claim 2 (depends on 1)

The isolated antibody, or antigen-binding fragment thereof, of claim 1, wherein the heavy chain variable (VH) region comprises the amino acid sequence set forth in SEQ ID NO: 17 or 18.

### Claim 3 (depends on 1)

The isolated antibody, or antigen-binding fragment thereof, of claim 1, wherein the light chain variable (VL) region comprises the amino acid sequence set forth in SEQ ID NO: 19.

### Claim 4 (depends on 1)

The isolated antibody, or an antigen-binding fragment thereof, of claim 1, that binds to human PD-L1, comprising a heavy chain variable (VH) region which comprises an amino acid sequence having at least 90% identity to the sequence set forth in SEQ ID NO: 17 or 18.

### Claim 5 (depends on 4)

The isolated antibody, or antigen-binding fragment thereof, of claim 4 comprising a light chain variable (VL) region which comprises an amino acid sequence having at least 90% identity to the sequence set forth in SEQ ID NO: 19.

### Claim 6 (depends on 1)

The isolated antibody, or an antigen-binding fragment thereof, of claim 1, that binds to human PD-L1, comprising a light chain variable (VL) region which comprises an amino acid sequence having at least 90% identity to the sequence set forth in SEQ ID NO: 19.

### Claim 7 (depends on 6)

The isolated antibody, or antigen binding fragment thereof, of claim 6, comprising a heavy chain variable (VH) region which comprises an amino acid sequence having at least 90% identity to from the sequence set forth in SEQ ID NO: 17 or 18.

### Claim 8 (depends on 1)

The isolated antibody, or antigen binding fragment thereof, of claim 1, wherein the VH region comprises SEQ ID NO: 17 or 18 and the VL region comprises SEQ ID NO: 19.

### Claim 9 (depends on 1)

The isolated antibody, or antigen binding fragment thereof, of claim 1, wherein the antibody is humanized.

### Claim 10 (depends on 1)

The isolated antibody, or antigen binding fragment thereof, of claim 1, wherein the antibody is selected from the group consisting of a single chain antibody, a scFv, a univalent antibody lacking a hinge region, a minibody, a Fab or a Fab′ fragment, a F(ab′)2 fragment, and a whole antibody.

### Claim 11 (depends on 1)

The isolated antibody, or antigen binding fragment thereof, of claim 1, comprising a human IgG constant domain.

### Claim 12 (depends on 11)

The isolated antibody, or antigen binding fragment thereof, of claim 11, wherein the IgG constant domain comprises an IgG1 CH1 domain.

### Claim 13 (depends on 11)

The isolated antibody, or antigen binding fragment thereof, of claim 11, wherein the IgG constant domain comprises an IgG1 Fc region.

### Claim 14 (depends on 1)

The isolated antibody, or antigen-binding fragment thereof, of claim 1, that binds PD-L1 with a KD of 0.4 nM or lower.

### Claim 15 (depends on 1)

The isolated antibody, or antigen-binding fragment thereof, of claim 1, wherein the isolated antibody, or antigen-binding fragment thereof:
(a) increases I cell activation;
(b) increases T cell proliferation;
(c) enhances interferon-gamma (IFN-γ) secretion; or
(d) a combination of any one or more of (a)-(c).

### Claim 16 (depends on 1)

The isolated antibody, or antigen-binding fragment thereof, of claim 1, that is a PD-L1 antagonist.

### Claim 17 (depends on 1)

The isolated antibody, or antigen-binding fragment thereof, of claim 1, that is a bi-specific antibody.

### Claim 18 (depends on 1)

An isolated polynucleotide encoding the isolated antibody, or antigen-binding fragment thereof, according to claim 1, an expression vector comprising the isolated polynucleotide, or a host cell comprising the vector.

### Claim 19 (depends on 1)

A composition comprising a physiologically acceptable carrier and a therapeutically effective amount of the isolated antibody, or antigen-binding fragment thereof, according to claim 1.

### Claim 20 (depends on 19)

A method for treating a patient having a cancer associated with aberrant PD-L1 expression or PD-L1-mediated immune suppression, comprising administering to the patient the composition of claim 19, thereby treating the cancer associated with aberrant PD-L1 expression.