Antibodies to ICOS

Abstract

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

1 . An isolated antibody that binds to ICOS, wherein the antibody comprises:
 i) (a) HCDR1 comprising the amino acid sequence of SEQ ID NO: 42; (b) HCDR2 comprising the amino acid sequence of SEQ ID NO: 43; (c) HCDR3 comprising the amino acid sequence of SEQ ID NO: 44; (d) LCDR1 comprising the amino acid sequence of SEQ ID NO: 45; (e) LCDR2 comprising the amino acid sequence of SEQ ID NO: 46; and (f) LCDR3 comprising the amino acid sequence of SEQ ID NO: 47; or   ii) (a) HCDR1 comprising an amino acid sequence selected from SEQ ID NOs: 32, 162, 172, and 182; (b) HCDR2 comprising an amino acid sequence selected from SEQ ID NOs: 33, 163, 173, and 183; (c) HCDR3 comprising an amino acid sequence selected from SEQ ID NOs: 34, 164, 174, and 184; (d) LCDR1 comprising an amino acid sequence selected from SEQ ID NOs: 35, 165, 175, and 185; (e) LCDR2 comprising an amino acid sequence selected from SEQ ID NOs: 36, 166, 176, and 186; and (f) LCDR3 comprising an amino acid sequence selected from SEQ ID NOs: 37, 167, 177, and 187; or   iii) (a) HCDR1 comprising an amino acid sequence selected from SEQ ID NOs: 52, 122, 132, 142, and 152; (b) HCDR2 comprising an amino acid sequence selected from SEQ ID NOs: 53, 123, 133, 143, and 153; (c) HCDR3 comprising an amino acid sequence selected from SEQ ID NOs: 54, 124, 134, 144, and 154; (d) LCDR1 comprising an amino acid sequence selected from SEQ ID NOs: 55, 125, 135, 145, and 155; (e) LCDR2 comprising an amino acid sequence selected from SEQ ID NOs: 56, 126, 136, 146, and 156; and (f) LCDR3 comprising an amino acid sequence selected from SEQ ID NOs: 57, 127, 137, 147, and 157; or   iv) (a) HCDR1 comprising the amino acid sequence of SEQ ID NO: 22; (b) HCDR2 comprising the amino acid sequence of SEQ ID NO: 23; (c) HCDR3 comprising the amino acid sequence of SEQ ID NO: 24; (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; or   v) (a) HCDR1 comprising the amino acid sequence of SEQ ID NO: 32; (b) HCDR2 comprising the amino acid sequence of SEQ ID NO: 33; (c) HCDR3 comprising the amino acid sequence of SEQ ID NO: 34; (d) LCDR1 comprising the amino acid sequence of SEQ ID NO: 35; (e) LCDR2 comprising the amino acid sequence of SEQ ID NO: 36; and (f) LCDR3 comprising the amino acid sequence of SEQ ID NO: 37; or   vi) (a) HCDR1 comprising the amino acid sequence of SEQ ID NO: 52; (b) HCDR2 comprising the amino acid sequence of SEQ ID NO: 53; (c) HCDR3 comprising the amino acid sequence of SEQ ID NO: 54; (d) LCDR1 comprising the amino acid sequence of SEQ ID NO: 55; (e) LCDR2 comprising the amino acid sequence of SEQ ID NO: 56; and (f) LCDR3 comprising the amino acid sequence of SEQ ID NO: 57; or   vii) (a) HCDR1 comprising the amino acid sequence of SEQ ID NO: 122; (b) HCDR2 comprising the amino acid sequence of SEQ ID NO: 123; (c) HCDR3 comprising the amino acid sequence of SEQ ID NO: 124; (d) LCDR1 comprising the amino acid sequence of SEQ ID NO: 125; (e) LCDR2 comprising the amino acid sequence of SEQ ID NO: 126; and (f) LCDR3 comprising the amino acid sequence of SEQ ID NO: 127; or   viii) (a) HCDR1 comprising the amino acid sequence of SEQ ID NO: 132; (b) HCDR2 comprising the amino acid sequence of SEQ ID NO: 133; (c) HCDR3 comprising the amino acid sequence of SEQ ID NO: 134; (d) LCDR1 comprising the amino acid sequence of SEQ ID NO: 135; (e) LCDR2 comprising the amino acid sequence of SEQ ID NO: 136; and (f) LCDR3 comprising the amino acid sequence of SEQ ID NO: 137; or (a) HCDR1 comprising the amino acid sequence of SEQ ID NO: 142; (b) HCDR2 comprising the amino acid sequence of SEQ ID NO: 143; (c) HCDR3 comprising the amino acid sequence of SEQ ID NO: 144; (d) LCDR1 comprising the amino acid sequence of SEQ ID NO: 145; (e) LCDR2 comprising the amino acid sequence of SEQ ID NO: 146; and (f) LCDR3 comprising the amino acid sequence of SEQ ID NO: 147; or   ix (a) HCDR1 comprising the amino acid sequence of SEQ ID NO: 152; (b) HCDR2 comprising the amino acid sequence of SEQ ID NO: 153; (c) HCDR3 comprising the amino acid sequence of SEQ ID NO: 154; (d) LCDR1 comprising the amino acid sequence of SEQ ID NO: 155; (e) LCDR2 comprising the amino acid sequence of SEQ ID NO: 156; and (f) LCDR3 comprising the amino acid sequence of SEQ ID NO: 157; or   x) (a) HCDR1 comprising the amino acid sequence of SEQ ID NO: 162; (b) HCDR2 comprising the amino acid sequence of SEQ ID NO: 163; (c) HCDR3 comprising the amino acid sequence of SEQ ID NO: 164; (d) LCDR1 comprising the amino acid sequence of SEQ ID NO: 165; (e) LCDR2 comprising the amino acid sequence of SEQ ID NO: 166; and (f) LCDR3 comprising the amino acid sequence of SEQ ID NO: 167; or   xi) (a) HCDR1 comprising the amino acid sequence of SEQ ID NO: 172; (b) HCDR2 comprising the amino acid sequence of SEQ ID NO: 173; (c) HCDR3 comprising the amino acid sequence of SEQ ID NO: 174; (d) LCDR1 comprising the amino acid sequence of SEQ ID NO: 175; (e) LCDR2 comprising the amino acid sequence of SEQ ID NO: 176; and (f) LCDR3 comprising the amino acid sequence of SEQ ID NO: 177; or   xii) (a) HCDR1 comprising the amino acid sequence of SEQ ID NO: 182; (b) HCDR2 comprising the amino acid sequence of SEQ ID NO: 183; (c) HCDR3 comprising the amino acid sequence of SEQ ID NO: 184; (d) LCDR1 comprising the amino acid sequence of SEQ ID NO: 185; (e) LCDR2 comprising the amino acid sequence of SEQ ID NO: 186; and (f) LCDR3 comprising the amino acid sequence of SEQ ID NO: 187.   
     
     
         2 . The antibody of  claim 1 , which comprises a heavy chain variable region (V H ) and a light chain variable region (V L ), wherein:
 i) the V H  is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 30 and the V L  is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 31; or   ii) the V H  is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 40 and the V L  is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 41; or   iii) the V H  is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 50 and the V L  is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 51; or   iv) the V H  is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 120 and the V L  is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 121; or   v) the V H  is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 130 and the V L  is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 131; or   vi) the V H  is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 140 and the V L  is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 141; or   vii) the V H  is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 150 and the V L  is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 151; or   viii) the V H  is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 160 and the V L  is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 161; or   ix) the V H  is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 170 and the V L  is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 171; or   x) the V H  is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 180 and the V L  is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 181.   
     
     
         3 . The antibody of  claim 1 , which comprises a heavy chain variable region (V H ) and a light chain variable region (V L ), wherein:
 i) the V H  comprises the amino acid sequence of SEQ ID NO: 30 and the V L  comprises the amino acid sequence of SEQ ID NO: 31; or   ii) the V H  comprises the amino acid sequence of SEQ ID NO: 40 and the V L  comprises the amino acid sequence of SEQ ID NO: 41; or   iii) the V H  comprises the amino acid sequence of SEQ ID NO: 50 and the V L  comprises the amino acid sequence of SEQ ID NO: 51; or   iv) the V H  comprises the amino acid sequence of SEQ ID NO: 120 and the V L  comprises the amino acid sequence of SEQ ID NO: 121; or   v) the V H  comprises the amino acid sequence of SEQ ID NO: 130 and the V L  comprises the amino acid sequence of SEQ ID NO: 131; or   vi) the V H  comprises the amino acid sequence of SEQ ID NO: 140 and the V L  comprises the amino acid sequence of SEQ ID NO: 141; or   vii) the V H  comprises the amino acid sequence of SEQ ID NO: 150 and the V L  comprises the amino acid sequence of SEQ ID NO: 151; or   viii) the V H  comprises the amino acid sequence of SEQ ID NO: 160 and the V L  comprises the amino acid sequence of SEQ ID NO: 161; or   ix) the V H  comprises the amino acid sequence of SEQ ID NO: 170 and the V L  comprises the amino acid sequence of SEQ ID NO: 171; or   x) the V H  comprises the amino acid sequence of SEQ ID NO: 180 and the V L  comprises the amino acid sequence of SEQ ID NO: 181.   
     
     
         4 . The antibody of  claim 1 , wherein the antibody is a monoclonal antibody. 
     
     
         5 . The antibody of  claim 1 , wherein the antibody is a chimeric antibody or a humanized antibody. 
     
     
         6 . The antibody of  claim 1 , wherein the antibody is an antibody fragment selected from a Fab, Fab′, Fv, scFv or (Fab′) 2  fragment or wherein the antibody is a full length antibody. 
     
     
         7 - 15 . (canceled) 
     
     
         16 . An isolated nucleic acid encoding the antibody of  claim 1 . 
     
     
         17 . A vector comprising the nucleic acid of  claim 16 . 
     
     
         18 . A host cell comprising the vector of  claim 17 . 
     
     
         19 . A host cell that produces the antibody of  claim 1 . 
     
     
         20 . A method for making an anti-ICOS antibody, comprising culturing the host cell of  claim 19  under conditions suitable for expression of the antibody, and recovering the antibody produced by the host cell. 
     
     
         21 . (canceled) 
     
     
         22 . A pharmaceutical composition comprising the anti-ICOS antibody of  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         23 . A method of treating cancer in a mammal comprising administering an effective amount of the pharmaceutical composition of  claim 22 . 
     
     
         24 . The method of  claim 23 , 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), and triple negative breast cancer (TNBC). 
     
     
         25 - 27 . (canceled) 
     
     
         28 . A method of activating T effector (Teff) cells in a mammal comprising administering an effective amount of the anti-ICOS antibody of the pharmaceutical composition of  claim 22 . 
     
     
         29 - 34 . (canceled) 
     
     
         35 . The method of  claim 24 , wherein the mammal is a human. 
     
     
         36 . The method of  claim 24 , wherein the mammal is administered at least one additional therapeutic agent, optionally wherein the additional therapeutic agent is selected from an anti-PD-1 antibody, an anti-PD-L1 antibody, and a cancer vaccine, wherein if the additional therapeutic agent is a cancer vaccine, 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. 
     
     
         37 - 59 . (canceled) 
     
     
         60 . An isolated antibody that binds to human ICOS, wherein the antibody also binds to mouse ICOS and/or rat ICOS. 
     
     
         61 - 97 . (canceled) 
     
     
         98 . A method of increasing the level of at least one chemokine and/or cytokine mRNA selected from GZMa, GZMb, CSF2, IL2, CXCL9, CXCL10, CXCL11, and CXCL13 in a mammal, comprising administering to the mammal an antibody of  claim 1 . 
     
     
         99 - 126 . (canceled) 
     
     
         127 . An antibody that binds to ICOS, wherein the antibody increases the level of the ligand for NKp46 (NKp46-L) on T cells. 
     
     
         128 - 134 . (canceled)