# US 2020/0399374 A1 · Anti-PD-1 Antibodies and Uses Thereof

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- Number: US 2020/0399374 A1
- Document ID: US20200399374A1
- Status: Published application
- Kind: A1
- Application number: 16/845,805
- Filed: 2020-04-10
- Published: 2020-12-24
- Earliest claimed: 2016-11-02
- Assignees: Jounce Therapeutics, Inc.
- Applicants: Jounce Therapeutics, Inc.
- Inventors: George Robert Mabry, III; Stephen Sazinsky
- Web page: https://patentgrep.com/patent/US20200399374A1

## CPC

- C07K 16/2818: {against CD28 or CD152}
- A61K 39/395: Antibodies (agglutinins A61K38/36 {; as drug carriers A61K47/50}); Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61P 35/00: Antineoplastic agents
- C07K 16/30: from tumour cells
- C12N 5/10: Cells modified by introduction of foreign genetic material
- C12N 15/00: Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor (mutants or genetically engineered microorganisms, per se C12N1/00, C12N5/00, C12N7/00; new plants per se A01H; plant reproduction by tissue culture techniques A01H4/00; new animals per se A01K67/00; use of medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases, gene therapy A61K48/00)
- C12N 15/64: General methods for preparing the vector, for introducing it into the cell or for selecting the vector-containing host
- C12N 15/66: General methods for inserting a gene into a vector to form a recombinant vector using cleavage and ligation; Use of non-functional linkers or adaptors, e.g. linkers containing the sequence for a restriction endonuclease
- 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 2317/33: Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
- 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 2317/52: Constant or Fc region; Isotype
- C07K 2317/54: F(ab')2
- C07K 2317/55: Fab or Fab'
- C07K 2317/56: variable (Fv) region, i.e. VH and/or VL
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/622: Single chain antibody (scFv)
- 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)
- 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
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## Abstract

Provided herein are various embodiments relating to antibodies. Some of the embodiments include antagonist antibodies that bind PD-1. Such antibodies can be used in methods to treat, for example, cancer.

## Claims

### Claim at position 1

1-50. (canceled)

### Claim 51

A method of treating cancer in a human subject comprising administering to the subject an effective amount of an anti-PD-1 antibody, wherein the anti-PD-1 antibody comprises (a) HCDR1 comprising the amino acid sequence of SEQ ID NO: 21; (b) HCDR2 comprising the amino acid sequence of SEQ ID NO: 22; (c) HCDR3 comprising the amino acid sequence of SEQ ID NO: 23; (d) LCDR1 comprising the amino acid sequence of SEQ ID NO: 25; (e) LCDR2 comprising the amino acid sequence of SEQ ID NO: 26; and (f) LCDR3 comprising the amino acid sequence of SEQ ID NO: 27.

### Claim 52 (depends on 51)

The method of claim 51, wherein the cancer is selected from melanoma, non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC), gastric cancer, bladder cancer, diffuse large B-cell lymphoma (DLBCL), Hodgkin's lymphoma, ovarian cancer, head & neck squamous cell cancer (HNSCC), mesothelioma, and triple negative breast cancer (TNBC).

### Claim 53 (depends on 52)

The method of claim 52, wherein the cancer is selected from melanoma, gastric cancer, head & neck squamous cell cancer (HNSCC), non-small cell lung cancer (NSCLC), and triple negative breast cancer (TNBC).

### Claim 54

A method of enhancing an immune response in a human subject comprising administering to the subject an effective amount of an anti-PD-1 antibody, wherein the anti-PD-1 antibody comprises (a) HCDR1 comprising the amino acid sequence of SEQ ID NO: 21; (b) HCDR2 comprising the amino acid sequence of SEQ ID NO: 22; (c) HCDR3 comprising the amino acid sequence of SEQ ID NO: 23; (d) LCDR1 comprising the amino acid sequence of SEQ ID NO: 25; (e) LCDR2 comprising the amino acid sequence of SEQ ID NO: 26; and (f) LCDR3 comprising the amino acid sequence of SEQ ID NO: 27.

### Claim 55

A method of increasing activation of a T cell in a human subject comprising administering to the subject an effective amount of an anti-PD-1 antibody, wherein the anti-PD-1 antibody comprises (a) HCDR1 comprising the amino acid sequence of SEQ ID NO: 21; (b) HCDR2 comprising the amino acid sequence of SEQ ID NO: 22; (c) HCDR3 comprising the amino acid sequence of SEQ ID NO: 23; (d) LCDR1 comprising the amino acid sequence of SEQ ID NO: 25; (e) LCDR2 comprising the amino acid sequence of SEQ ID NO: 26; and (f) LCDR3 comprising the amino acid sequence of SEQ ID NO: 27.

### Claim 56

A method of reducing tumor size in a human subject with cancer comprising administering to the subject an effective amount of an anti-PD-1 antibody, wherein the anti-PD-1 antibody comprises (a) HCDR1 comprising the amino acid sequence of SEQ ID NO: 21; (b) HCDR2 comprising the amino acid sequence of SEQ ID NO: 22; (c) HCDR3 comprising the amino acid sequence of SEQ ID NO: 23; (d) LCDR1 comprising the amino acid sequence of SEQ ID NO: 25; (e) LCDR2 comprising the amino acid sequence of SEQ ID NO: 26; and (f) LCDR3 comprising the amino acid sequence of SEQ ID NO: 27.

### Claim 57

(canceled)

### Claim 58 (depends on 51)

The method of claim 51, wherein the subject is administered at least one additional therapeutic agent.

### Claim 59 (depends on 58)

The method of claim 58, wherein the additional therapeutic agent is administered concurrently or sequentially with the anti-PD-1 antibody.

### Claim 60 (depends on 58)

The method of claim 58 wherein the additional therapeutic agent is selected from an anti-ICOS antibody and an anti-CTLA4 antibody.

### Claim 61 (depends on 60)

The method of claim 60, wherein the additional therapeutic agent is an anti-ICOS antibody.

### Claim 62 (depends on 58)

The method of claim 58, wherein the additional therapeutic agent is a cancer vaccine.

### Claim 63 (depends on 62)

The method of claim 62, wherein the cancer vaccine is selected from a DNA vaccine, an engineered virus vaccine, an engineered tumor cell vaccine, and a cancer vaccine developed using neoantigens.

### Claim at position 15

64-84. (canceled)

### Claim 85

A method of increasing the level of at least one cytokine selected from IFNγ and IL-2 in a human subject, comprising administering to the subject an anti-PD-1 antibody, wherein the anti-PD-1 antibody comprises (a) HCDR1 comprising the amino acid sequence of SEQ ID NO: 21; (b) HCDR2 comprising the amino acid sequence of SEQ ID NO: 22; (c) HCDR3 comprising the amino acid sequence of SEQ ID NO: 23; (d) LCDR1 comprising the amino acid sequence of SEQ ID NO: 25; (e) LCDR2 comprising the amino acid sequence of SEQ ID NO: 26; and (f) LCDR3 comprising the amino acid sequence of SEQ ID NO: 27.

### Claim 86 (depends on 85)

The method of claim 85, wherein the level of the cytokine is measured 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 8 hours, 10 hours, 12 hours, 14 hours, 16 hours, 18 hours, 20 hours, 22 hours, 24 hours, 36 hours, or 48 hours after administration of the antibody.

### Claim 87 (depends on 85)

The method of claim 85, wherein at least one cytokine is IFNγ.

### Claim 88 (depends on 85)

The method of claim 85, wherein at least one cytokine is IL-2.

### Claim 89 (depends on 85)

The method of claim 85, wherein the level of the cytokine is measured 24 hours after administration of the antibody.

### Claim 90

(canceled)

### Claim 91 (depends on 90)

The method of claim 90, wherein the human has cancer.

### Claim 92 (depends on 91)

The method of claim 91, wherein the cancer is selected from melanoma, non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC), gastric cancer, bladder cancer, diffuse large B-cell lymphoma (DLBCL), Hodgkin's lymphoma, ovarian cancer, head & neck squamous cell cancer (HNSCC), mesothelioma, and triple negative breast cancer (TNBC).

### Claim 93 (depends on 92)

The method of claim 92, wherein the cancer is selected from melanoma, gastric cancer, head & neck squamous cell cancer (HNSCC), non-small cell lung cancer (NSCLC), and triple negative breast cancer (TNBC).

### Claim 94 (depends on 85)

The method of claim 85, wherein an immune response is enhanced following administration of the anti-PD-1 antibody.

### Claim 95

The method of laim 85, wherein activation of T cells is increased following administration of the anti-PD-1 antibody.

### Claim 96 (depends on 85)

The method of claim 85, wherein tumor size is decreased following administration of the anti-PD-1 antibody.

### Claim 97 (depends on 85)

The method of claim 85, wherein the subject is administered at least one additional therapeutic agent.

### Claim 98 (depends on 97)

The method of claim 97, wherein the additional therapeutic agent is administered concurrently or sequentially with the anti-PD-1 antibody.

### Claim 99 (depends on 97)

The method of claim 97, wherein the additional therapeutic agent is selected from an anti-ICOS antibody and an anti-CTLA4 antibody.

### Claim 100 (depends on 99)

The method of claim 99, wherein the additional therapeutic is an anti-ICOS antibody.

### Claim 101 (depends on 97)

The method of claim 97, wherein the additional therapeutic agent is a cancer vaccine.

### Claim 102 (depends on 101)

The method of claim 101, wherein the cancer vaccine is selected from a DNA vaccine, an engineered virus vaccine, an engineered tumor cell vaccine, and a cancer vaccine developed using neoantigens.

### Claim 103 (depends on 51)

The method of claim 51, wherein a sample of the cancer has been determined to express PD-1.

### Claim 104 (depends on 103)

The method of claim 103, wherein the sample shows 1+, 2+, or 3+ staining of PD-1 by immunohistochemistry (IHC).

### Claim 105 (depends on 51)

The method of claim 51, wherein the sample has been determined to have an elevated level of PD-L1.

### Claim 106 (depends on 105)

The method of claim 105, wherein PD-L1 levels are determined using IHC.

### Claim 107 (depends on 51)

The method of claim 51, wherein the anti-PD-1 antibody comprises a heavy chain variable region (VH) that is at least 90% identical to the amino acid sequence of SEQ ID NO: 20 and a light chain variable region (VL) that is at least 90% identical to the amino acid sequence of SEQ ID NO: 24.

### Claim 108 (depends on 51)

The method of claim 51, wherein the anti-PD-1 antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 20 and a VL comprising the amino acid sequence of SEQ ID NO: 24.

### Claim 109 (depends on 51)

The method of claim 51, wherein the anti-PD-1 antibody binds to human PD-1 with an affinity (KD) of less than 5 nM.

### Claim 110 (depends on 109)

The method of claim 109, wherein affinity is determined using biolayer interferometry.

### Claim 111 (depends on 51)

The method of claim 51, wherein the anti-PD-1 antibody is an antibody fragment selected from a Fab, Fab′, Fv, scFv or (Fab′)2 fragment.

### Claim 112 (depends on 51)

The method of claim 51, wherein the anti-PD-1 antibody is a full length antibody.

### Claim 113 (depends on 54)

The method of claim 54, wherein the anti-PD-1 antibody comprises a heavy chain variable region (VH) that is at least 90% identical to the amino acid sequence of SEQ ID NO: 20 and a light chain variable region (VL) that is at least 90% identical to the amino acid sequence of SEQ ID NO: 24.

### Claim 114 (depends on 54)

The method of claim 54, wherein the anti-PD-1 antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 20 and a VL comprising the amino acid sequence of SEQ ID NO: 24.

### Claim 115 (depends on 54)

The method of claim 54, wherein the anti-PD-1 antibody binds to human PD-1 with an affinity (KD) of less than 5 nM.

### Claim 116 (depends on 115)

The method of claim 115, wherein affinity is determined using biolayer interferometry.

### Claim 117 (depends on 54)

The method of claim 54, wherein the anti-PD-1 antibody is an antibody fragment selected from a Fab, Fab′, Fv, scFv or (Fab′)2 fragment.

### Claim 118 (depends on 54)

The method of claim 54, wherein the anti-PD-1 antibody is a full length antibody.

### Claim 119 (depends on 55)

The method of claim 55, wherein the anti-PD-1 antibody comprises a heavy chain variable region (VH) that is at least 90% identical to the amino acid sequence of SEQ ID NO: 20 and a light chain variable region (VL) that is at least 90% identical to the amino acid sequence of SEQ ID NO: 24.

### Claim 120 (depends on 55)

The method of claim 55, wherein the anti-PD-1 antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 20 and a VL comprising the amino acid sequence of SEQ ID NO: 24.

### Claim 121 (depends on 55)

The method of claim 55, wherein the anti-PD-1 antibody binds to human PD-1 with an affinity (KD) of less than 5 nM.

### Claim 122 (depends on 121)

The method of claim 121, wherein affinity is determined using biolayer interferometry.

### Claim 123 (depends on 55)

The method of claim 55, wherein the anti-PD-1 antibody is an antibody fragment selected from a Fab, Fab′, Fv, scFv or (Fab′)2 fragment.

### Claim 124 (depends on 55)

The method of claim 55, wherein the anti-PD-1 antibody is a full length antibody.

### Claim 125 (depends on 56)

The method of claim 56, wherein the anti-PD-1 antibody comprises a heavy chain variable region (VH) that is at least 90% identical to the amino acid sequence of SEQ ID NO: 20 and a light chain variable region (VL) that is at least 90% identical to the amino acid sequence of SEQ ID NO: 24.

### Claim 126 (depends on 56)

The method of claim 56, wherein the anti-PD-1 antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 20 and a VL comprising the amino acid sequence of SEQ ID NO: 24.

### Claim 127 (depends on 56)

The method of claim 56, wherein the anti-PD-1 antibody binds to human PD-1 with an affinity (KD) of less than 5 nM.

### Claim 128 (depends on 127)

The method of claim 127, wherein affinity is determined using biolayer interferometry.

### Claim 129 (depends on 56)

The method of claim 56, wherein the anti-PD-1 antibody is an antibody fragment selected from a Fab, Fab′, Fv, scFv or (Fab′)2 fragment.

### Claim 130 (depends on 56)

The method of claim 56, wherein the anti-PD-1 antibody is a full length antibody.

### Claim 131 (depends on 85)

The method of claim 85, wherein the anti-PD-1 antibody comprises a heavy chain variable region (VH) that is at least 90% identical to the amino acid sequence of SEQ ID NO: 20 and a light chain variable region (VL) that is at least 90% identical to the amino acid sequence of SEQ ID NO: 24.

### Claim 132 (depends on 85)

The method of claim 85, wherein the anti-PD-1 antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 20 and a VL comprising the amino acid sequence of SEQ ID NO: 24.

### Claim 133 (depends on 85)

The method of claim 85, wherein the anti-PD-1 antibody binds to human PD-1 with an affinity (KD) of less than 5 nM.

### Claim 134 (depends on 133)

The method of claim 133, wherein affinity is determined using biolayer interferometry.

### Claim 135 (depends on 85)

The method of claim 85, wherein the anti-PD-1 antibody is an antibody fragment selected from a Fab, Fab′, Fv, scFv or (Fab′)2 fragment.

### Claim 136 (depends on 85)

The method of claim 85, wherein the anti-PD-1 antibody is a full length antibody.