Anti-ALK antibodies and methods for use thereof
Provided herein are compositions, methods and uses involving antibodies that specifically bind to ALK, a receptor tyrosine kinase, and modulate the expression and/or activity of ALK. Also provided are uses and methods for treating, e.g., managing, disorders, such as cancer.
1. An antibody or an antigen-binding fragment thereof, which specifically binds to an anaplastic lymphoma kinase (ALK) extracellular domain (ECD), comprising:
(i) a light chain variable region (VL) comprising:
(a) a VL complementarity determining region (CDR) 1 comprising the amino acid sequence of KASQNVGTNVA (SEQ ID NO: 13);
(b) a VL CDR2 comprising the amino acid sequence of SASYRYS (SEQ ID NO: 14); and
(c) a VL CDR3 comprising the amino acid sequence of QX 1 YNSYPYMX 2 T (SEQ ID NO: 468), wherein X 1 is Q or R and X 2 is Y or F; and
(ii) a heavy chain variable region (VH) comprising:
(a) a VH CDR1 comprising the amino acid sequence X 3 YWMH (SEQ ID NO: 469), wherein X 3 is N or S;
(b) a VH CDR2 comprising the amino acid sequence of YIX 4 PSSGYTKYNQKFKD (SEQ ID NO: 470), wherein X 4 is N or K; and
(c) a VH CDR3 comprising the amino acid sequence of DYYGSSSWFAY (SEQ ID NO: 18).
2. The antibody or antigen-binding fragment thereof of claim 1 , wherein the VL comprises:
(a) a VL CDR1 comprising the amino acid sequence of KASQNVGTNVA (SEQ ID NO: 13);
(b) a VL CDR2 comprising the amino acid sequence of SASYRYS (SEQ ID NO: 14); and
(c) a VL CDR3 comprising the amino acid sequence of QQYNSYPYMYT (SEQ ID NO: 15);
and wherein the VH comprises:
(d) a VH CDR1 comprising the amino acid sequence of NYWMH (SEQ ID NO: 16);
(e) a VH CDR2 comprising the amino acid sequence of YINPSSGYTKYNQKFKD (SEQ ID NO: 17); and
(f) a VH CDR3 comprising the amino acid sequence of DYYGSSSWFAY (SEQ ID NO: 18).
3. The antibody or antigen-binding fragment thereof of claim 1 , wherein the VL comprises the amino acid sequence of SEQ ID NO: 399 and the VH comprises the amino acid sequence of SEQ ID NO: 400.
4. The antibody or antigen-binding fragment thereof of claim 1 , which comprises a heavy chain constant region.
5. The antibody or antigen-binding fragment thereof of claim 4 , wherein the heavy chain constant region is a human IgG constant region.
6. The antibody or antigen-binding fragment thereof of claim 1 , which comprises a light chain constant region selected from the group consisting of a human kappa constant region and a human lambda constant region.
7. The antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody is a human antibody, a humanized antibody, a chimeric antibody, a recombinant antibody, a multispecific antibody, or an antigen-binding fragment thereof; wherein the antigen-binding fragment is an Fv, Fab, F(ab′)2, Fab′, dsFv, scFv, or sc(Fv)2.
8. The antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody is a monoclonal antibody.
9. A composition comprising the antibody or antigen-binding fragment thereof of claim 1 , and a pharmaceutically acceptable carrier.
10. A method of inhibiting the proliferation of a cell expressing ALK, said method comprising contacting the cell with the antibody or antigen-binding fragment thereof of claim 1 .