# US 2020/0399385 A1 · Antibodies against ox-40 and uses thereof

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- Number: US 2020/0399385 A1
- Document ID: US20200399385A1
- Status: Published application
- Kind: A1
- Application number: 16/847,130
- Filed: 2020-04-13
- Published: 2020-12-24
- Earliest claimed: 2015-05-29
- Assignees: Bristol-Myers Squibb Company
- Applicants: Bristol-Myers Squibb Company
- Inventors: Zhehong CAI; Indrani CHAKRABORTY; Marie-Michelle Navarro GARCIA; Thomas D. KEMPE; Alan J. KORMAN; Alexander T. KOZHICH; Hadia LEMAR; Mark MAURER; Christina Maria MILBURN; Michael QUIGLEY; Xiang SHAO; Mohan SRINIVASAN; Kent THUDIUM; Susan Chien-Szu WONG; Jochem GOKEMEIJER; Xi-Tao WANG; Han CHANG; Patrick GUIRNALDA
- Web page: https://patentgrep.com/patent/US20200399385A1

## CPC

- C07K 16/2878: {against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95}
- A61K 39/3955: {against proteinaceous materials, e.g. enzymes, hormones, lymphokines}
- A61P 35/00: Antineoplastic agents
- C07K 16/30: from tumour cells
- C07K 16/3023: {Lung}
- C07K 16/3038: {Kidney, bladder}
- C07K 16/3069: {Reproductive system, e.g. ovaria, uterus, testes, prostate}
- G01N 33/575: for cancer
- A61K 2039/505: {comprising antibodies}
- A61K 2039/507: {Comprising a combination of two or more separate antibodies}
- C07K 16/2818: {against CD28 or CD152}
- 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 2317/31: multispecific
- 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 2317/56: variable (Fv) region, i.e. VH and/or VL
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/567: Framework region [FR]
- C07K 2317/73: Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
- C07K 2317/74: Inducing cell proliferation
- 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 2317/94: Stability, e.g. half-life, pH, temperature or enzyme-resistance
- G01N 2333/70514: CD4
- 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
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

Provided herein are antibodies, or antigen binding portions thereof, that bind to OX40. Also provided are uses of these proteins in therapeutic applications, such as in the treatment of cancer. Further provided are cells that produce the antibodies, polynucleotides encoding the heavy and/or light chain variable region of the antibodies, and vectors comprising the polynucleotides encoding the heavy and/or light chain variable region of the antibodies.

## Claims

### Claim at position 1

1-20. (canceled)

### Claim 21

A method of stimulating an antigen-specific T cell response comprising contacting an antigen-specific T cell with an isolated antibody that binds to human OX40 (“anti-OX40 antibody”), such that an antigen-specific T cell response is stimulated, and wherein the anti-OX40 antibody comprises:
(a) a heavy chain variable region CDR1 comprising the sequence of SEQ ID NO: 87, a heavy chain variable region CDR2 comprising the sequence of SEQ ID NO: 317, and a heavy chain variable region CDR3 comprising the sequence of SEQ ID NO: 89, and a light chain variable region CDR1 comprising the sequence of SEQ ID NO: 90, a light chain variable region CDR2 comprising the sequence of SEQ ID NO: 91, and a light chain variable region CDR3 comprising the sequence of SEQ ID NO: 92;
(b) a heavy chain variable region CDR1 comprising the sequence of SEQ ID NO: 11, a heavy chain variable region CDR2 comprising the sequence of SEQ ID NO: 12, and a heavy chain variable region CDR3 comprising the sequence of SEQ ID NO: 13, and a light chain variable region CDR1 comprising the sequence of SEQ ID NO: 14, a light chain variable region CDR2 comprising the sequence of SEQ ID NO: 15, and a light chain variable region CDR3 comprising the sequence of SEQ ID NO: 16;
(c) a heavy chain variable region CDR1 comprising the sequence of SEQ ID NO: 19, a heavy chain variable region CDR2 comprising the sequence of SEQ ID NO: 20, and a heavy chain variable region CDR3 comprising the sequence of SEQ ID NO: 21, and a light chain variable region CDR1 comprising the sequence of SEQ ID NO: 22, a light chain variable region CDR2 comprising the sequence of SEQ ID NO: 23, and a light chain variable region CDR3 comprising the sequence of SEQ ID NO: 24;
(d) a heavy chain variable region CDR1 comprising the sequence of SEQ ID NO: 19, a heavy chain variable region CDR2 comprising the sequence of SEQ ID NO: 20, and a heavy chain variable region CDR3 comprising the sequence of SEQ ID NO: 21, and a light chain variable region CDR1 comprising the sequence of SEQ ID NO: 25, a light chain variable region CDR2 comprising the sequence of SEQ ID NO: 26, and a light chain variable region CDR3 comprising the sequence of SEQ ID NO: 27;
(e) a heavy chain variable region CDR1 comprising the sequence of SEQ ID NO: 31, a heavy chain variable region CDR2 comprising the sequence of SEQ ID NO: 32, and a heavy chain variable region CDR3 comprising the sequence of SEQ ID NO: 33, and a light chain variable region CDR1 comprising the sequence of SEQ ID NO: 34, a light chain variable region CDR2 comprising the sequence of SEQ ID NO: 35, and a light chain variable region CDR3 comprising the sequence of SEQ ID NO: 36;
(f) a heavy chain variable region CDR1 comprising the sequence of SEQ ID NO: 39, a heavy chain variable region CDR2 comprising the sequence of SEQ ID NO: 40, and a heavy chain variable region CDR3 comprising the sequence of SEQ ID NO: 41, and a light chain variable region CDR1 comprising the sequence of SEQ ID NO: 42, a light chain variable region CDR2 comprising the sequence of SEQ ID NO: 43, and a light chain variable region CDR3 comprising the sequence of SEQ ID NO: 44;
(g) a heavy chain variable region CDR1 comprising the sequence of SEQ ID NO: 39, a heavy chain variable region CDR2 comprising the sequence of SEQ ID NO: 40, and a heavy chain variable region CDR3 comprising the sequence of SEQ ID NO: 41, and a light chain variable region CDR1 comprising the sequence of SEQ ID NO: 45, a light chain variable region CDR2 comprising the sequence of SEQ ID NO: 46, and a light chain variable region CDR3 comprising the sequence of SEQ ID NO: 47;
(h) a heavy chain variable region CDR1 comprising the sequence of SEQ ID NO: 51, a heavy chain variable region CDR2 comprising the sequence of SEQ ID NO: 52, and a heavy chain variable region CDR3 comprising the sequence of SEQ ID NO: 53, and a light chain variable region CDR1 comprising the sequence of SEQ ID NO: 54, a light chain variable region CDR2 comprising the sequence of SEQ ID NO: 55, and a light chain variable region CDR3 comprising the sequence of SEQ ID NO: 56;
(i) a heavy chain variable region CDR1 comprising the sequence of SEQ ID NO: 59, a heavy chain variable region CDR2 comprising the sequence of SEQ ID NO: 60, and a heavy chain variable region CDR3 comprising the sequence of SEQ ID NO: 61, and a light chain variable region CDR1 comprising the sequence of SEQ ID NO: 62, a light chain variable region CDR2 comprising the sequence of SEQ ID NO: 63, and a light chain variable region CDR3 comprising the sequence of SEQ ID NO: 64;
(j) a heavy chain variable region CDR1 comprising the sequence of SEQ ID NO: 67, a heavy chain variable region CDR2 comprising the sequence of SEQ ID NO: 68, and a heavy chain variable region CDR3 comprising the sequence of SEQ ID NO: 69, and a light chain variable region CDR1 comprising the sequence of SEQ ID NO: 70, a light chain variable region CDR2 comprising the sequence of SEQ ID NO: 71, and a light chain variable region CDR3 comprising the sequence of SEQ ID NO: 72;
(k) a heavy chain variable region CDR1 comprising the sequence of SEQ ID NO: 75, a heavy chain variable region CDR2 comprising the sequence of SEQ ID NO: 76, and a heavy chain variable region CDR3 comprising the sequence of SEQ ID NO: 77, and a light chain variable region CDR1 comprising the sequence of SEQ ID NO: 78, a light chain variable region CDR2 comprising the sequence of SEQ ID NO: 79, and a light chain variable region CDR3 comprising the sequence of SEQ ID NO: 80, wherein, optionally, the Asp-Gly sequence in SEQ ID NO: 76 is replaced with an amino acid sequence that does not under isomerization;
(l) a heavy chain variable region CDR1 comprising the sequence of SEQ ID NO: 75, a heavy chain variable region CDR2 comprising the sequence of SEQ ID NO: 76, and a heavy chain variable region CDR3 comprising the sequence of SEQ ID NO: 77, and a light chain variable region CDR1 comprising the sequence of SEQ ID NO: 81, a light chain variable region CDR2 comprising the sequence of SEQ ID NO: 82, and a light chain variable region CDR3 comprising the sequence of SEQ ID NO: 83; or
(m) a heavy chain variable region CDR1 comprising the sequence of SEQ ID NO: 87, a heavy chain variable region CDR2 comprising the sequence of SEQ ID NO: 88, and a heavy chain variable region CDR3 comprising the sequence of SEQ ID NO: 89, and a light chain variable region CDR1 comprising the sequence of SEQ ID NO: 90, a light chain variable region CDR2 comprising the sequence of SEQ ID NO: 91, and a light chain variable region CDR3 comprising the sequence of SEQ ID NO: 92.

### Claim at position 3

22-25. (canceled)

### Claim 26

A method of reducing or depleting the number of T regulatory cells in a tumor of a subject in need thereof comprising administering to the subject a therapeutically effective amount of an isolated antibody that binds to human OX40 (“anti-OX40 antibody”), such that the number of T regulatory cells is reduced or depleted, and wherein the anti-OX40 antibody comprises:
(a) a heavy chain variable region CDR1 comprising the sequence of SEQ ID NO: 87, a heavy chain variable region CDR2 comprising the sequence of SEQ ID NO: 317, and a heavy chain variable region CDR3 comprising the sequence of SEQ ID NO: 89, and a light chain variable region CDR1 comprising the sequence of SEQ ID NO: 90, a light chain variable region CDR2 comprising the sequence of SEQ ID NO: 91, and a light chain variable region CDR3 comprising the sequence of SEQ ID NO: 92;
(b) a heavy chain variable region CDR1 comprising the sequence of SEQ ID NO: 11, a heavy chain variable region CDR2 comprising the sequence of SEQ ID NO: 12, and a heavy chain variable region CDR3 comprising the sequence of SEQ ID NO: 13, and a light chain variable region CDR1 comprising the sequence of SEQ ID NO: 14, a light chain variable region CDR2 comprising the sequence of SEQ ID NO: 15, and a light chain variable region CDR3 comprising the sequence of SEQ ID NO: 16;
(c) a heavy chain variable region CDR1 comprising the sequence of SEQ ID NO: 19, a heavy chain variable region CDR2 comprising the sequence of SEQ ID NO: 20, and a heavy chain variable region CDR3 comprising the sequence of SEQ ID NO: 21, and a light chain variable region CDR1 comprising the sequence of SEQ ID NO: 22, a light chain variable region CDR2 comprising the sequence of SEQ ID NO: 23, and a light chain variable region CDR3 comprising the sequence of SEQ ID NO: 24;
(d) a heavy chain variable region CDR1 comprising the sequence of SEQ ID NO: 19, a heavy chain variable region CDR2 comprising the sequence of SEQ ID NO: 20, and a heavy chain variable region CDR3 comprising the sequence of SEQ ID NO: 21, and a light chain variable region CDR1 comprising the sequence of SEQ ID NO: 25, a light chain variable region CDR2 comprising the sequence of SEQ ID NO: 26, and a light chain variable region CDR3 comprising the sequence of SEQ ID NO: 27;
(e) a heavy chain variable region CDR1 comprising the sequence of SEQ ID NO: 31, a heavy chain variable region CDR2 comprising the sequence of SEQ ID NO: 32, and a heavy chain variable region CDR3 comprising the sequence of SEQ ID NO: 33, and a light chain variable region CDR1 comprising the sequence of SEQ ID NO: 34, a light chain variable region CDR2 comprising the sequence of SEQ ID NO: 35, and a light chain variable region CDR3 comprising the sequence of SEQ ID NO: 36;
(f) a heavy chain variable region CDR1 comprising the sequence of SEQ ID NO: 39, a heavy chain variable region CDR2 comprising the sequence of SEQ ID NO: 40, and a heavy chain variable region CDR3 comprising the sequence of SEQ ID NO: 41, and a light chain variable region CDR1 comprising the sequence of SEQ ID NO: 42, a light chain variable region CDR2 comprising the sequence of SEQ ID NO: 43, and a light chain variable region CDR3 comprising the sequence of SEQ ID NO: 44;
(g) a heavy chain variable region CDR1 comprising the sequence of SEQ ID NO: 39, a heavy chain variable region CDR2 comprising the sequence of SEQ ID NO: 40, and a heavy chain variable region CDR3 comprising the sequence of SEQ ID NO: 41, and a light chain variable region CDR1 comprising the sequence of SEQ ID NO: 45, a light chain variable region CDR2 comprising the sequence of SEQ ID NO: 46, and a light chain variable region CDR3 comprising the sequence of SEQ ID NO: 47;
(h) a heavy chain variable region CDR1 comprising the sequence of SEQ ID NO: 51, a heavy chain variable region CDR2 comprising the sequence of SEQ ID NO: 52, and a heavy chain variable region CDR3 comprising the sequence of SEQ ID NO: 53, and a light chain variable region CDR1 comprising the sequence of SEQ ID NO: 54, a light chain variable region CDR2 comprising the sequence of SEQ ID NO: 55, and a light chain variable region CDR3 comprising the sequence of SEQ ID NO: 56;
(i) a heavy chain variable region CDR1 comprising the sequence of SEQ ID NO: 59, a heavy chain variable region CDR2 comprising the sequence of SEQ ID NO: 60, and a heavy chain variable region CDR3 comprising the sequence of SEQ ID NO: 61, and a light chain variable region CDR1 comprising the sequence of SEQ ID NO: 62, a light chain variable region CDR2 comprising the sequence of SEQ ID NO: 63, and a light chain variable region CDR3 comprising the sequence of SEQ ID NO: 64;
(j) a heavy chain variable region CDR1 comprising the sequence of SEQ ID NO: 67, a heavy chain variable region CDR2 comprising the sequence of SEQ ID NO: 68, and a heavy chain variable region CDR3 comprising the sequence of SEQ ID NO: 69, and a light chain variable region CDR1 comprising the sequence of SEQ ID NO: 70, a light chain variable region CDR2 comprising the sequence of SEQ ID NO: 71, and a light chain variable region CDR3 comprising the sequence of SEQ ID NO: 72;
(k) a heavy chain variable region CDR1 comprising the sequence of SEQ ID NO: 75, a heavy chain variable region CDR2 comprising the sequence of SEQ ID NO: 76, and a heavy chain variable region CDR3 comprising the sequence of SEQ ID NO: 77, and a light chain variable region CDR1 comprising the sequence of SEQ ID NO: 78, a light chain variable region CDR2 comprising the sequence of SEQ ID NO: 79, and a light chain variable region CDR3 comprising the sequence of SEQ ID NO: 80, wherein, optionally, the Asp-Gly sequence in SEQ ID NO: 76 is replaced with an amino acid sequence that does not under isomerization;
(l) a heavy chain variable region CDR1 comprising the sequence of SEQ ID NO: 75, a heavy chain variable region CDR2 comprising the sequence of SEQ ID NO: 76, and a heavy chain variable region CDR3 comprising the sequence of SEQ ID NO: 77, and a light chain variable region CDR1 comprising the sequence of SEQ ID NO: 81, a light chain variable region CDR2 comprising the sequence of SEQ ID NO: 82, and a light chain variable region CDR3 comprising the sequence of SEQ ID NO: 83; or
(m) a heavy chain variable region CDR1 comprising the sequence of SEQ ID NO: 87, a heavy chain variable region CDR2 comprising the sequence of SEQ ID NO: 88, and a heavy chain variable region CDR3 comprising the sequence of SEQ ID NO: 89, and a light chain variable region CDR1 comprising the sequence of SEQ ID NO: 90, a light chain variable region CDR2 comprising the sequence of SEQ ID NO: 91, and a light chain variable region CDR3 comprising the sequence of SEQ ID NO: 92.

### Claim 27

A method of inhibiting the growth of tumor cells in a subject in need thereof comprising administering to the subject a therapeutically effective amount of an isolated antibody that binds to human OX40 (“anti-OX40 antibody”), such that the growth of tumor cells is inhibited, and wherein the anti-OX40 antibody comprises:
(a) a heavy chain variable region CDR1 comprising the sequence of SEQ ID NO: 87, a heavy chain variable region CDR2 comprising the sequence of SEQ ID NO: 317, and a heavy chain variable region CDR3 comprising the sequence of SEQ ID NO: 89, and a light chain variable region CDR1 comprising the sequence of SEQ ID NO: 90, a light chain variable region CDR2 comprising the sequence of SEQ ID NO: 91, and a light chain variable region CDR3 comprising the sequence of SEQ ID NO: 92;
(b) a heavy chain variable region CDR1 comprising the sequence of SEQ ID NO: 11, a heavy chain variable region CDR2 comprising the sequence of SEQ ID NO: 12, and a heavy chain variable region CDR3 comprising the sequence of SEQ ID NO: 13, and a light chain variable region CDR1 comprising the sequence of SEQ ID NO: 14, a light chain variable region CDR2 comprising the sequence of SEQ ID NO: 15, and a light chain variable region CDR3 comprising the sequence of SEQ ID NO: 16;
(c) a heavy chain variable region CDR1 comprising the sequence of SEQ ID NO: 19, a heavy chain variable region CDR2 comprising the sequence of SEQ ID NO: 20, and a heavy chain variable region CDR3 comprising the sequence of SEQ ID NO: 21, and a light chain variable region CDR1 comprising the sequence of SEQ ID NO: 22, a light chain variable region CDR2 comprising the sequence of SEQ ID NO: 23, and a light chain variable region CDR3 comprising the sequence of SEQ ID NO: 24;
(d) a heavy chain variable region CDR1 comprising the sequence of SEQ ID NO: 19, a heavy chain variable region CDR2 comprising the sequence of SEQ ID NO: 20, and a heavy chain variable region CDR3 comprising the sequence of SEQ ID NO: 21, and a light chain variable region CDR1 comprising the sequence of SEQ ID NO: 25, a light chain variable region CDR2 comprising the sequence of SEQ ID NO: 26, and a light chain variable region CDR3 comprising the sequence of SEQ ID NO: 27;
(e) a heavy chain variable region CDR1 comprising the sequence of SEQ ID NO: 31, a heavy chain variable region CDR2 comprising the sequence of SEQ ID NO: 32, and a heavy chain variable region CDR3 comprising the sequence of SEQ ID NO: 33, and a light chain variable region CDR1 comprising the sequence of SEQ ID NO: 34, a light chain variable region CDR2 comprising the sequence of SEQ ID NO: 35, and a light chain variable region CDR3 comprising the sequence of SEQ ID NO: 36;
(f) a heavy chain variable region CDR1 comprising the sequence of SEQ ID NO: 39, a heavy chain variable region CDR2 comprising the sequence of SEQ ID NO: 40, and a heavy chain variable region CDR3 comprising the sequence of SEQ ID NO: 41, and a light chain variable region CDR1 comprising the sequence of SEQ ID NO: 42, a light chain variable region CDR2 comprising the sequence of SEQ ID NO: 43, and a light chain variable region CDR3 comprising the sequence of SEQ ID NO: 44;
(g) a heavy chain variable region CDR1 comprising the sequence of SEQ ID NO: 39, a heavy chain variable region CDR2 comprising the sequence of SEQ ID NO: 40, and a heavy chain variable region CDR3 comprising the sequence of SEQ ID NO: 41, and a light chain variable region CDR1 comprising the sequence of SEQ ID NO: 45, a light chain variable region CDR2 comprising the sequence of SEQ ID NO: 46, and a light chain variable region CDR3 comprising the sequence of SEQ ID NO: 47;
(h) a heavy chain variable region CDR1 comprising the sequence of SEQ ID NO: 51, a heavy chain variable region CDR2 comprising the sequence of SEQ ID NO: 52, and a heavy chain variable region CDR3 comprising the sequence of SEQ ID NO: 53, and a light chain variable region CDR1 comprising the sequence of SEQ ID NO: 54, a light chain variable region CDR2 comprising the sequence of SEQ ID NO: 55, and a light chain variable region CDR3 comprising the sequence of SEQ ID NO: 56;
(i) a heavy chain variable region CDR1 comprising the sequence of SEQ ID NO: 59, a heavy chain variable region CDR2 comprising the sequence of SEQ ID NO: 60, and a heavy chain variable region CDR3 comprising the sequence of SEQ ID NO: 61, and a light chain variable region CDR1 comprising the sequence of SEQ ID NO: 62, a light chain variable region CDR2 comprising the sequence of SEQ ID NO: 63, and a light chain variable region CDR3 comprising the sequence of SEQ ID NO: 64;
(j) a heavy chain variable region CDR1 comprising the sequence of SEQ ID NO: 67, a heavy chain variable region CDR2 comprising the sequence of SEQ ID NO: 68, and a heavy chain variable region CDR3 comprising the sequence of SEQ ID NO: 69, and a light chain variable region CDR1 comprising the sequence of SEQ ID NO: 70, a light chain variable region CDR2 comprising the sequence of SEQ ID NO: 71, and a light chain variable region CDR3 comprising the sequence of SEQ ID NO: 72;
(k) a heavy chain variable region CDR1 comprising the sequence of SEQ ID NO: 75, a heavy chain variable region CDR2 comprising the sequence of SEQ ID NO: 76, and a heavy chain variable region CDR3 comprising the sequence of SEQ ID NO: 77, and a light chain variable region CDR1 comprising the sequence of SEQ ID NO: 78, a light chain variable region CDR2 comprising the sequence of SEQ ID NO: 79, and a light chain variable region CDR3 comprising the sequence of SEQ ID NO: 80, wherein, optionally, the Asp-Gly sequence in SEQ ID NO: 76 is replaced with an amino acid sequence that does not under isomerization;
(l) a heavy chain variable region CDR1 comprising the sequence of SEQ ID NO: 75, a heavy chain variable region CDR2 comprising the sequence of SEQ ID NO: 76, and a heavy chain variable region CDR3 comprising the sequence of SEQ ID NO: 77, and a light chain variable region CDR1 comprising the sequence of SEQ ID NO: 81, a light chain variable region CDR2 comprising the sequence of SEQ ID NO: 82, and a light chain variable region CDR3 comprising the sequence of SEQ ID NO: 83; or
(m) a heavy chain variable region CDR1 comprising the sequence of SEQ ID NO: 87, a heavy chain variable region CDR2 comprising the sequence of SEQ ID NO: 88, and a heavy chain variable region CDR3 comprising the sequence of SEQ ID NO: 89, and a light chain variable region CDR1 comprising the sequence of SEQ ID NO: 90, a light chain variable region CDR2 comprising the sequence of SEQ ID NO: 91, and a light chain variable region CDR3 comprising the sequence of SEQ ID NO: 92.

### Claim 28 (depends on 21)

The method of claim 21, wherein the anti-OX40 antibody comprises:
(a) a heavy chain variable region comprising the sequence of SEQ ID NO: 318 and a light chain variable region comprising the sequence of SEQ ID NO: 94;
(b) a heavy chain variable region comprising the sequence of SEQ ID NO: 17 and a light chain variable region comprising the sequence of SEQ ID NO: 18;
(c) a heavy chain variable region comprising the sequence of SEQ ID NO: 28 and a light chain variable region comprising the sequence of SEQ ID NO: 29;
(d) a heavy chain variable region comprising the sequence of SEQ ID NO: 28 and a light chain variable region comprising the sequence of SEQ ID NO: 30;
(e) a heavy chain variable region comprising the sequence of SEQ ID NO: 37 and a light chain variable region comprising the sequence of SEQ ID NO: 38;
(f) a heavy chain variable region comprising the sequence of SEQ ID NO: 48 and a light chain variable region comprising the sequence of SEQ ID NO: 49;
(g) a heavy chain variable region comprising the sequence of SEQ ID NO: 48 and a light chain variable region comprising the sequence of SEQ ID NO: 50;
(h) a heavy chain variable region comprising the sequence of SEQ ID NO: 57 and a light chain variable region comprising the sequence of SEQ ID NO: 58;
(i) a heavy chain variable region comprising the sequence of SEQ ID NO: 65 and a light chain variable region comprising the sequence of SEQ ID NO: 66;
(j) a heavy chain variable region comprising the sequence of SEQ ID NO: 73 and a light chain variable region comprising the sequence of SEQ ID NO: 74;
(k) a heavy chain variable region comprising the sequence of SEQ ID NO: 84 and a light chain variable region comprising the sequence of SEQ ID NO: 85;
(l) a heavy chain variable region comprising the sequence of SEQ ID NO: 84 and a light chain variable region comprising the sequence of SEQ ID NO: 86; or
(m) a heavy chain variable region comprising the sequence of SEQ ID NO: 93 and a light chain variable region comprising the sequence of SEQ ID NO: 94.

### Claim 29 (depends on 26)

The method of claim 26, wherein the anti-OX40 antibody comprises:
(a) a heavy chain variable region comprising the sequence of SEQ ID NO: 318 and a light chain variable region comprising the sequence of SEQ ID NO: 94;
(b) a heavy chain variable region comprising the sequence of SEQ ID NO: 17 and a light chain variable region comprising the sequence of SEQ ID NO: 18;
(c) a heavy chain variable region comprising the sequence of SEQ ID NO: 28 and a light chain variable region comprising the sequence of SEQ ID NO: 29;
(d) a heavy chain variable region comprising the sequence of SEQ ID NO: 28 and a light chain variable region comprising the sequence of SEQ ID NO: 30;
(e) a heavy chain variable region comprising the sequence of SEQ ID NO: 37 and a light chain variable region comprising the sequence of SEQ ID NO: 38;
(f) a heavy chain variable region comprising the sequence of SEQ ID NO: 48 and a light chain variable region comprising the sequence of SEQ ID NO: 49;
(g) a heavy chain variable region comprising the sequence of SEQ ID NO: 48 and a light chain variable region comprising the sequence of SEQ ID NO: 50;
(h) a heavy chain variable region comprising the sequence of SEQ ID NO: 57 and a light chain variable region comprising the sequence of SEQ ID NO: 58;
(i) a heavy chain variable region comprising the sequence of SEQ ID NO: 65 and a light chain variable region comprising the sequence of SEQ ID NO: 66;
(j) a heavy chain variable region comprising the sequence of SEQ ID NO: 73 and a light chain variable region comprising the sequence of SEQ ID NO: 74;
(k) a heavy chain variable region comprising the sequence of SEQ ID NO: 84 and a light chain variable region comprising the sequence of SEQ ID NO: 85;
(l) a heavy chain variable region comprising the sequence of SEQ ID NO: 84 and a light chain variable region comprising the sequence of SEQ ID NO: 86; or
(m) a heavy chain variable region comprising the sequence of SEQ ID NO: 93 and a light chain variable region comprising the sequence of SEQ ID NO: 94.

### Claim 30 (depends on 27)

The method of claim 27, wherein the anti-OX40 antibody comprises:
(a) a heavy chain variable region comprising the sequence of SEQ ID NO: 318 and a light chain variable region comprising the sequence of SEQ ID NO: 94;
(b) a heavy chain variable region comprising the sequence of SEQ ID NO: 17 and a light chain variable region comprising the sequence of SEQ ID NO: 18;
(c) a heavy chain variable region comprising the sequence of SEQ ID NO: 28 and a light chain variable region comprising the sequence of SEQ ID NO: 29;
(d) a heavy chain variable region comprising the sequence of SEQ ID NO: 28 and a light chain variable region comprising the sequence of SEQ ID NO: 30;
(e) a heavy chain variable region comprising the sequence of SEQ ID NO: 37 and a light chain variable region comprising the sequence of SEQ ID NO: 38;
(f) a heavy chain variable region comprising the sequence of SEQ ID NO: 48 and a light chain variable region comprising the sequence of SEQ ID NO: 49;
(g) a heavy chain variable region comprising the sequence of SEQ ID NO: 48 and a light chain variable region comprising the sequence of SEQ ID NO: 50;
(h) a heavy chain variable region comprising the sequence of SEQ ID NO: 57 and a light chain variable region comprising the sequence of SEQ ID NO: 58;
(i) a heavy chain variable region comprising the sequence of SEQ ID NO: 65 and a light chain variable region comprising the sequence of SEQ ID NO: 66;
(j) a heavy chain variable region comprising the sequence of SEQ ID NO: 73 and a light chain variable region comprising the sequence of SEQ ID NO: 74;
(k) a heavy chain variable region comprising the sequence of SEQ ID NO: 84 and a light chain variable region comprising the sequence of SEQ ID NO: 85;
(l) a heavy chain variable region comprising the sequence of SEQ ID NO: 84 and a light chain variable region comprising the sequence of SEQ ID NO: 86; or
(m) a heavy chain variable region comprising the sequence of SEQ ID NO: 93 and a light chain variable region comprising the sequence of SEQ ID NO: 94.

### Claim 31 (depends on 21)

The method of claim 21, wherein the anti-OX40 antibody comprises:
(a) a heavy chain comprising the sequence of SEQ ID NO: 124 and a light chain comprising the sequence of SEQ ID NO: 116;
(b) a heavy chain comprising the sequence of SEQ ID NO: 95 and a light chain comprising the sequence of SEQ ID NO: 96;
(c) a heavy chain comprising the sequence of SEQ ID NO: 97 and a light chain comprising the sequence of SEQ ID NO: 98;
(d) a heavy chain comprising the sequence of SEQ ID NO: 99 and a light chain comprising the sequence of SEQ ID NO: 100;
(e) a heavy chain comprising the sequence of SEQ ID NO: 101 and a light chain comprising the sequence of SEQ ID NO: 102;
(f) a heavy chain comprising the sequence of SEQ ID NO: 103 and a light chain comprising the sequence of SEQ ID NO: 104;
(g) a heavy chain comprising the sequence of SEQ ID NO: 105 and a light chain comprising the sequence of SEQ ID NO: 106;
(h) a heavy chain comprising the sequence of SEQ ID NO: 107 and a light chain comprising the sequence of SEQ ID NO: 108;
(i) a heavy chain comprising the sequence of SEQ ID NO: 109 and a light chain comprising the sequence of SEQ ID NO: 110;
(j) a heavy chain comprising the sequence of SEQ ID NO: 111 and a light chain comprising the sequence of SEQ ID NO: 112;
(k) a heavy chain comprising the sequence of SEQ ID NO: 113 and a light chain comprising the sequence of SEQ ID NO: 114;
(l) a heavy chain comprising the sequence of SEQ ID NO: 115 and a light chain comprising the sequence of SEQ ID NO: 116;
(m) a heavy chain comprising the sequence of SEQ ID NO: 117 and a light chain comprising the sequence of SEQ ID NO: 118;
(n) a heavy chain comprising the sequence of SEQ ID NO: 119 and a light chain comprising the sequence of SEQ ID NO: 120;
(o) a heavy chain comprising the sequence of SEQ ID NO: 121 and a light chain comprising the sequence of SEQ ID NO: 122;
(p) a heavy chain comprising the sequence of SEQ ID NO: 123 and a light chain comprising the sequence of SEQ ID NO: 116; or
(q) a heavy chain comprising the sequence of SEQ ID NO: 125 and a light chain comprising the sequence of SEQ ID NO: 116.

### Claim 32 (depends on 26)

The method of claim 26, wherein the anti-OX40 antibody comprises:
(a) a heavy chain comprising the sequence of SEQ ID NO: 124 and a light chain comprising the sequence of SEQ ID NO: 116;
(b) a heavy chain comprising the sequence of SEQ ID NO: 95 and a light chain comprising the sequence of SEQ ID NO: 96;
(c) a heavy chain comprising the sequence of SEQ ID NO: 97 and a light chain comprising the sequence of SEQ ID NO: 98;
(d) a heavy chain comprising the sequence of SEQ ID NO: 99 and a light chain comprising the sequence of SEQ ID NO: 100;
(e) a heavy chain comprising the sequence of SEQ ID NO: 101 and a light chain comprising the sequence of SEQ ID NO: 102;
(f) a heavy chain comprising the sequence of SEQ ID NO: 103 and a light chain comprising the sequence of SEQ ID NO: 104;
(g) a heavy chain comprising the sequence of SEQ ID NO: 105 and a light chain comprising the sequence of SEQ ID NO: 106;
(h) a heavy chain comprising the sequence of SEQ ID NO: 107 and a light chain comprising the sequence of SEQ ID NO: 108;
(i) a heavy chain comprising the sequence of SEQ ID NO: 109 and a light chain comprising the sequence of SEQ ID NO: 110;
(j) a heavy chain comprising the sequence of SEQ ID NO: 111 and a light chain comprising the sequence of SEQ ID NO: 112;
(k) a heavy chain comprising the sequence of SEQ ID NO: 113 and a light chain comprising the sequence of SEQ ID NO: 114;
(l) a heavy chain comprising the sequence of SEQ ID NO: 115 and a light chain comprising the sequence of SEQ ID NO: 116;
(m) a heavy chain comprising the sequence of SEQ ID NO: 117 and a light chain comprising the sequence of SEQ ID NO: 118;
(n) a heavy chain comprising the sequence of SEQ ID NO: 119 and a light chain comprising the sequence of SEQ ID NO: 120;
(o) a heavy chain comprising the sequence of SEQ ID NO: 121 and a light chain comprising the sequence of SEQ ID NO: 122;
(p) a heavy chain comprising the sequence of SEQ ID NO: 123 and a light chain comprising the sequence of SEQ ID NO: 116; or
(q) a heavy chain comprising the sequence of SEQ ID NO: 125 and a light chain comprising the sequence of SEQ ID NO: 116.

### Claim 33 (depends on 27)

The method of claim 27, wherein the anti-OX40 antibody comprises:
(a) a heavy chain comprising the sequence of SEQ ID NO: 124 and a light chain comprising the sequence of SEQ ID NO: 116;
(b) a heavy chain comprising the sequence of SEQ ID NO: 95 and a light chain comprising the sequence of SEQ ID NO: 96;
(c) a heavy chain comprising the sequence of SEQ ID NO: 97 and a light chain comprising the sequence of SEQ ID NO: 98;
(d) a heavy chain comprising the sequence of SEQ ID NO: 99 and a light chain comprising the sequence of SEQ ID NO: 100;
(e) a heavy chain comprising the sequence of SEQ ID NO: 101 and a light chain comprising the sequence of SEQ ID NO: 102;
(f) a heavy chain comprising the sequence of SEQ ID NO: 103 and a light chain comprising the sequence of SEQ ID NO: 104;
(g) a heavy chain comprising the sequence of SEQ ID NO: 105 and a light chain comprising the sequence of SEQ ID NO: 106;
(h) a heavy chain comprising the sequence of SEQ ID NO: 107 and a light chain comprising the sequence of SEQ ID NO: 108;
(i) a heavy chain comprising the sequence of SEQ ID NO: 109 and a light chain comprising the sequence of SEQ ID NO: 110;
(j) a heavy chain comprising the sequence of SEQ ID NO: 111 and a light chain comprising the sequence of SEQ ID NO: 112;
(k) a heavy chain comprising the sequence of SEQ ID NO: 113 and a light chain comprising the sequence of SEQ ID NO: 114;
(l) a heavy chain comprising the sequence of SEQ ID NO: 115 and a light chain comprising the sequence of SEQ ID NO: 116;
(m) a heavy chain comprising the sequence of SEQ ID NO: 117 and a light chain comprising the sequence of SEQ ID NO: 118;
(n) a heavy chain comprising the sequence of SEQ ID NO: 119 and a light chain comprising the sequence of SEQ ID NO: 120;
(o) a heavy chain comprising the sequence of SEQ ID NO: 121 and a light chain comprising the sequence of SEQ ID NO: 122;
(p) a heavy chain comprising the sequence of SEQ ID NO: 123 and a light chain comprising the sequence of SEQ ID NO: 116; or
(q) a heavy chain comprising the sequence of SEQ ID NO: 125 and a light chain comprising the sequence of SEQ ID NO: 116.

### Claim 34 (depends on 21)

The method of claim 21, wherein the contacting is performed in vitro.

### Claim 35 (depends on 21)

The method of claim 21, wherein the contacting is performed in a subject in vivo.

### Claim 36 (depends on 21)

The method of claim 21, wherein the antigen-specific T cell comprises an effector T cell (Teff cell), helper T cell (Th cell), cytotoxic T cell (Tc cell), or combinations thereof.

### Claim 37 (depends on 35)

The method of claim 35, wherein the subject has a cancer.

### Claim 38 (depends on 35)

The method of claim 35, comprising administering one or more additional therapeutics to the subject.

### Claim 39 (depends on 38)

The method of claim 38, wherein the one or more additional therapeutics comprise an anti-PD-1 antibody, an anti-PD-L1 antibody, an anti-LAG-3 antibody, an anti-CTLA-4 antibody, anti-TGFβ antibody, or combinations thereof.

### Claim 40 (depends on 26)

The method of claim 26, comprising administering one or more additional therapeutics to the subject.

### Claim 41 (depends on 40)

The method of claim 40, wherein the one or more additional therapeutics comprise an anti-PD-1 antibody, an anti-PD-L1 antibody, an anti-LAG-3 antibody, an anti-CTLA-4 antibody, anti-TGFβ antibody, or combinations thereof.

### Claim 42 (depends on 27)

The method of claim 27, comprising administering one or more additional therapeutics to the subject.

### Claim 43 (depends on 42)

The method of claim 42, wherein the one or more additional therapeutics comprise an anti-PD-1 antibody, an anti-PD-L1 antibody, an anti-LAG-3 antibody, an anti-CTLA-4 antibody, anti-TGFβ antibody, or combinations thereof.

### Claim 44 (depends on 37)

The method of claim 37, wherein the cancer is selected from a cervical cancer, bladder cancer, colorectal cancer, ovarian cancer, non-small lung cancer, squamous cell carcinoma of the head and neck, or combinations thereof.