Antibodies for epidermal growth factor receptor 3 (her3)
AssigneeNovartis AG
InventorsWinfried ELIS, Seth Alexander ETTENBERG, Andrew Paul GARNER, Nicole HAUBST, Christian Carsten Silvester KUNZ, Elizabeth Anne Reisinger SPRAGUE
Life of this patent
Estimating the term…
Abstract
The present invention relates to antibodies or fragments thereof that target a conformational epitope of a HER receptor. In particular, the invention relates to antibodies or fragments thereof that target a conformational epitope of HER3 receptor and compositions and methods of use thereof.
Claims42
An isolated antibody or fragment thereof that recognizes a conformational epitope of a HER3 receptor, wherein the conformational epitope comprises amino acid residues within domain 2 and domain 4 of the HER3 receptor, and wherein the antibody or fragment thereof blocks both ligand-dependent and ligand-independent signal transduction.
An isolated antibody or fragment thereof that recognizes a conformational epitope of a HER3 receptor, wherein the conformational epitope comprises amino acid residues within domain 2 and domain 4 of the HER3 receptor, wherein binding of the antibody or fragment thereof to the HER3 receptor in the absence of a HER3 ligand reduces ligand-independent formation of a HER2-HER3 protein complex in a cell which expresses HER2 and HER3.
An isolated antibody or fragment thereof that recognizes a conformational epitope of a HER3 receptor, wherein the conformational epitope comprises amino acid residues within domain 2 and domain 4 of the HER3 receptor, wherein binding of the antibody or fragment thereof to the HER3 receptor in the presence of a HER3 ligand reduces ligand-dependent formation of a HER2-HER3 protein complex in a cell which expresses HER2 and HER3.
An isolated antibody or fragment thereof that recognizes a conformational epitope of a HER3 receptor, wherein the conformational epitope comprises amino acid residues within domain 2 and domain 4 of the HER3 receptor, and wherein the antibody or fragment thereof inhibits phosphorylation of HER3 as assessed by HER3 ligand-dependent phosphorylation assay.
An isolated antibody or fragment thereof to a HER3 receptor, having a dissociation (KD) of at least 1×107M−1, 108M−1, 109M−1, 1010 M−1, 1011 M−1, 1012M−1, 1013 M−1.
An isolated antibody or fragment thereof, binds to the same conformational epitope as an antibody described in Table 1.
An isolated antibody or fragment thereof that cross-competes with an antibody described in Table 1.
An isolated antibody or fragment thereof to HER3 receptor comprising a heavy chain CDR3 selected from the group consisting of SEQ ID NO:
- 4, SEQ ID NO:
- 10, SEQ ID NO:
- 22, SEQ ID NO:
- 28, SEQ ID NO:
- 40, SEQ ID NO:
- 46, SEQ ID NO:
- 58, SEQ ID NO:
- 64, SEQ ID NO:
- 76, SEQ ID NO:
- 82, SEQ ID NO:
- 94, SEQ ID NO:
- 100, SEQ ID NO:
- 112, SEQ ID NO:
- 118, SEQ ID NO:
- 130, SEQ ID NO:
- 136, SEQ ID NO:
- 148, SEQ ID NO:
- 166, SEQ ID NO:
- 184, SEQ ID NO:
- 202, SEQ ID NO:
- 220, SEQ ID NO:
- 238, SEQ ID NO:
- 256, SEQ ID NO:
- 274, SEQ ID NO:
- 292, SEQ ID NO:
- 310, SEQ ID NO:
- 328, SEQ ID NO:
- 346, and SEQ ID NO:
- 364.
An isolated antibody or fragment thereof to HER3 receptor which antibody comprises a VH selected from the group consisting of SEQ ID NO:
- 15, SEQ ID NO:
- 33, SEQ ID NO:
- 51, SEQ ID NO:
- 69, SEQ ID NO:
- 87, SEQ ID NO:
- 105, SEQ ID NO:
- 123, SEQ ID NO:
- 141, SEQ ID NO:
- 159, SEQ ID NO:
- 177, SEQ ID NO:
- 195, SEQ ID NO:
- 213, SEQ ID NO:
- 231, SEQ ID NO:
- 249, SEQ ID NO:
- 267, SEQ ID NO:
- 285, SEQ ID NO:
- 303, SEQ ID NO:
- 321, SEQ ID NO:
- 339, SEQ ID NO:
- 357, and SEQ ID NO:
- 375;
- and a VL selected from the group consisting of SEQ ID NO:
- 14, SEQ ID NO:
- 32, SEQ ID NO:
- 50, SEQ ID NO:
- 68, SEQ ID NO:
- 86, SEQ ID NO:
- 104, SEQ ID NO:
- 122, SEQ ID NO:
- 140, SEQ ID NO:
- 158, SEQ ID NO:
- 176, SEQ ID NO:
- 194, SEQ ID NO:
- 212, SEQ ID NO:
- 230, SEQ ID NO:
- 248, SEQ ID NO:
- 266, SEQ ID NO:
- 284, SEQ ID NO:
- 302, SEQ ID NO:
- 320, SEQ ID NO:
- 338, SEQ ID NO:
- 356, and SEQ ID NO:
- 374 or an amino acid sequence with 97-99% identity thereof.
An isolated antibody or fragment thereof comprising a variable heavy chain sequence having SEQ ID NO:
- 493.
An isolated antibody or fragment thereof comprising a variable light chain sequence having SEQ ID NO:
- 494.
An isolated antibody or fragment thereof comprising a variable heavy chain sequence having SEQ ID NO:
- 493 and a variable light chain sequence having SEQ ID NO:
- 494.
An isolated antibody or fragment thereof to HER3 receptor with a variant heavy chain variable region comprising CDR1, CDR2, and CDR3, wherein the variant has at least one to four amino acid changes in one of CDR1, CDR2, or CDR3.
An isolated antibody or fragment thereof, comprising a heavy chain variable region CDR1 selected from the group consisting of SEQ ID NO:
- 2, 20, 38, 56, 74, 92, 110, 128, 146, 164, 182, 200, 218, 236, 254, 272, 290, 308, 326, 344, and 362;
- CDR2 selected from the group consisting of SEQ ID NO:
- 3, 21, 39, 57, 75, 93, 111, 129, 147, 165, 183, 201, 219, 237, 255, 273, 291, 309, 327, 345, and 363;
- CDR3 selected from the group consisting of SEQ ID NO:
- 4, 22, 40, 58, 76, 94, 112, 130, 148, 166, 184, 202, 220, 238, 256, 274, 292, 310, 328, 346, and 364;
- a light chain variable region CDR1 selected from the group consisting of SEQ ID NO:
- 5, 23, 41, 59, 77, 95, 113, 131, 149, 167, 185, 203, 221, 239, 257, 275, 293, 311, 329, 347, and 365;
- CDR2 selected from the group consisting of SEQ ID NO:
- 6, 24, 42, 60, 78, 96, 114, 132, 150, 166, 186, 204, 222, 240, 258, 276, 294, 312, 330, 348, and 366;
- and CDR3 selected from the group consisting of SEQ ID NO:
- 7, 25, 43, 61, 79, 97, 115, 133, 151, 169, 187, 205, 223, 241, 259, 277, 295, 313, 331, 349, and 367.
An isolated antibody or fragment thereof, comprising a heavy chain variable region CDR1 of SEQ ID NO:
- 128;
- CDR2 of SEQ ID NO:
- 129;
- CDR3 of SEQ ID NO:
- 130;
- a light chain variable region CDR1 of SEQ ID NO:
- 131;
- CDR2 of SEQ ID NO:
- 132;
- and CDR3 of SEQ ID NO:
- 133.
A fragment of an antibody that binds to HER3 selected from the group consisting of;
- Fab, F(ab2)′, F(ab)2′, scFv, VHH, VH, VL, dAbs.
A pharmaceutical composition comprising an antibody or fragment thereof and a pharmaceutically acceptable carrier.
A method of treating a cancer comprising selecting a subject having an HER3 expressing cancer, administering to the subject an effective amount of a composition comprising an antibody or fragment thereof disclosed in Table 1.
Dependencies are inferred from the claim text.