# US 10,370,448 B2 · Human anti-PD-1, PD-L1, and PD-L2 antibodies and uses therefor

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- Number: US 10,370,448 B2
- Document ID: US10370448B2
- Status: Granted
- Kind: B2
- Application number: 15/995,584
- Filed: 2018-06-01
- Published: 2018-12-27
- Granted: 2019-08-06
- Earliest claimed: 2008-09-26
- Assignees: Emory University; Dana-Farber Cancer Institute, Inc.
- Applicants: Dana-Farber Cancer Institute, Inc.; Emory University
- Inventors: Gordon J. Freeman; Rafi Ahmed; Timothy D. Jones; Francis J. Carr; James P. Gregson
- Web page: https://patentgrep.com/patent/US10370448B2

## CPC

- C07K 16/2803: {against the immunoglobulin superfamily}
- A61P 1/04: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A61P 1/16: for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- A61P 3/00: Drugs for disorders of the metabolism (of the blood or the extracellular fluid A61P7/00)
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- A61P 7/06: Antianaemics
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 11/06: Antiasthmatics
- A61P 17/00: Drugs for dermatological disorders
- A61P 17/06: Antipsoriatics
- A61P 19/02: for joint disorders, e.g. arthritis, arthrosis
- A61P 21/00: Drugs for disorders of the muscular or neuromuscular system
- A61P 21/04: for myasthenia gravis
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 31/00: Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P 31/04: Antibacterial agents
- A61P 31/12: Antivirals
- A61P 31/14: for RNA viruses
- A61P 31/16: for influenza or rhinoviruses
- A61P 31/18: for HIV
- A61P 31/20: for DNA viruses
- A61P 31/22: for herpes viruses
- A61P 33/00: Antiparasitic agents
- A61P 33/02: Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
- A61P 33/06: Antimalarials
- A61P 33/10: Anthelmintics
- A61P 33/12: Schistosomicides
- A61P 35/00: Antineoplastic agents
- A61P 35/02: specific for leukemia
- A61P 37/02: Immunomodulators
- A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07K 16/2818: {against CD28 or CD152}
- C07K 16/2827: {against B7 molecules, e.g. CD80, CD86}
- A61K 2039/505: {comprising antibodies}
- C07K 2317/21: from primates, e.g. man
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- C07K 2317/34: Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
- C07K 2317/74: Inducing cell proliferation
- 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
- Y02A 50/30: Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
- 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
- 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)
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE

## Abstract

The present invention is based, in part, on the identification of novel human anti-PD-1, PD-L1, and PD-L2 antibodies. Accordingly, the invention relates to compositions and methods for diagnosing, prognosing, and treating conditions that would benefit from modulating PD-1, PD-1, and/or PD-L2 activity (e.g., persistent infectious diseases autoimmune diseases, asthma, transplant rejection, inflammatory disorders and tumors) using the novel human anti-PD-1, PD-L1, and PD-L2 antibodies described herein.

## Claims

### Claim 1

An isolated nucleic acid encoding an isolated antibody or an antigen-binding fragment thereof, wherein the isolated antibody or antigen-binding fragment thereof comprises:
a) a heavy chain variable region sequence comprising three CDRs with the sequences of SEQ ID NOs: 13-15; and/or
b) a light chain variable region sequence comprising three CDRs with the sequences of SEQ ID NOs:16-18, and
wherein the isolated antibody or antigen-binding fragment thereof binds to a PD-L1 protein comprising the amino acid sequence of SEQ ID NO: 4, and wherein the isolated antibody or antigen-binding fragment thereof is chimeric, humanized, composite, or human.

### Claim 2 (depends on 1)

The isolated nucleic acid of claim 1, wherein the isolated antibody or antigen-binding fragment thereof comprises:
a) a heavy chain variable region sequence comprising three CDRs with the sequences of SEQ ID NOs: 13-15; and
b) a light chain variable region sequence comprising three CDRs with the sequences of SEQ ID NOs:16-18.

### Claim 3 (depends on 2)

The isolated nucleic acid of claim 2, wherein the isolated antibody or antigen-binding fragment thereof comprises:
a) a heavy chain variable region sequence selected from the group consisting of SEQ ID NOs: 34-38, or a sequence with at least about 95% homology to a heavy chain variable region sequence selected from the group consisting of SEQ ID NOs: 34-38; and
b) a light chain variable region sequence selected from the group consisting of SEQ ID NOs: 39-42, or a sequence with at least about 95% homology to a light chain variable region sequence selected from the group consisting of SEQ ID NOs: 39-42.

### Claim 4 (depends on 1)

The isolated nucleic acid of claim 1, wherein the isolated antibody or antigen-binding fragment thereof comprises:
a) a heavy chain variable region sequence selected from the group consisting of SEQ ID NOs: 34-38, or a sequence with at least about 95% homology to a heavy chain variable region sequence selected from the group consisting of SEQ ID NOs: 34-38; and/or
b) a light chain variable region sequence selected from the group consisting of SEQ ID NOs: 39-42, or a sequence with at least about 95% homology to a light chain variable region sequence selected from the group consisting of SEQ ID NOs: 39-42.

### Claim 5 (depends on 4)

The isolated nucleic acid of claim 4, wherein the isolated antibody or antigen-binding fragment thereof comprises:
a) a heavy chain variable region sequence selected from the group consisting of SEQ ID NOs: 34-38; and/or
b) a light chain variable region sequence selected from the group consisting of SEQ ID NOs: 39-42.

### Claim 6 (depends on 5)

The isolated nucleic acid of claim 5, wherein the isolated antibody or antigen-binding fragment thereof comprises:
a) a heavy chain variable region sequence selected from the group consisting of SEQ ID NOs: 34-38; and
b) a light chain variable region sequence selected from the group consisting of SEQ ID NOs: 39-42.

### Claim 7 (depends on 6)

The isolated nucleic acid of claim 6, wherein the isolated antibody or antigen-binding fragment thereof comprises:
a) a heavy chain variable region sequence comprising SEQ ID NO: 35 or 37; and
b) a light chain variable region sequence comprising SEQ ID NO: 39, 40 or 42.

### Claim 8 (depends on 2)

The isolated nucleic acid of claim 2, wherein the isolated antibody or antigen-binding fragment thereof comprises:
a) a heavy chain variable region sequence comprising SEQ ID NO: 35 or 37, or a sequence with at least about 95% homology to a heavy chain variable region sequence comprising SEQ ID NO: 35 or 37; and
b) a light chain variable region sequence comprising SEQ ID NO: 39, 40 or 42, or a sequence with at least about 95% homology to a light chain variable region sequence comprising SEQ ID NO: 39, 40 or 42.

### Claim 9 (depends on 1)

The isolated nucleic acid of claim 1, wherein the isolated antibody or antigen-binding fragment thereof inhibits the binding of an antibody comprising a heavy chain variable region comprising the sequence of SEQ ID NO:78 and a light chain variable region comprising the sequence of SEQ ID NO:79 to Fc-PD-L1.

### Claim 10 (depends on 1)

The isolated nucleic acid of claim 1, wherein the isolated antibody or antigen-binding fragment thereof inhibits a PD-L1-mediated signal.

### Claim 11 (depends on 1)

A vector comprising the isolated nucleic acid of claim 1.

### Claim 12 (depends on 1)

A host cell comprising the nucleic acid of claim 1.

### Claim 13

An isolated nucleic acid that hybridizes, under stringent conditions, with the complement of a nucleic acid encoding a polypeptide comprising a sequence selected from the group consisting of SEQ ID NOs: 34-42, or a sequence with at least about 95% homology to a nucleic acid encoding a polypeptide comprising a sequence selected from the group consisting of SEQ ID NOs: 34-42, wherein the polypeptide
is an isolated antibody or an antigen-binding fragment thereof
binds to a PD-L1 protein comprising the amino acid sequence of SEQ ID NO: 4; and
is chimeric, humanized, composite, or human.

### Claim 14 (depends on 13)

A vector comprising the isolated nucleic acid of claim 13.

### Claim 15 (depends on 13)

A host cell comprising the nucleic acid of claim 13.

### Claim 16

An isolated nucleic acid encoding a polypeptide, wherein the polypeptide
is an isolated antibody or an antigen-binding fragment thereof;
binds to a PD-L1 protein comprising the amino acid sequence of SEQ ID NO:4;
is chimeric, humanized, composite, or human; and
comprises a sequence selected from the group consisting of SEQ ID NOs: 34-42, or a sequence with at least about 95% homology to a sequence selected from the group consisting of SEQ ID NOs: 34-42.

### Claim 17 (depends on 16)

A vector comprising the isolated nucleic acid of claim 16.

### Claim 18 (depends on 16)

A host cell comprising the nucleic acid of claim 16.