Humanized anti-cmet antagonists
AssigneeGenentech, Inc.
InventorsMark Dennis, Karen Billeci, Judy Young, Zhong Zheng
Life of this patent
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Abstract
The invention provides therapeutic anti-c-met antibodies, and compositions comprising and methods of using these antibodies.
Claims54
An anti-c-met antibody comprising:
- (a) at least one HVR sequence selected from the group consisting of:
- (i) HVR-L1 comprising sequence A1-A17, wherein A1-A17 is KSSQSLLYTSSQKNYLA (SEQ ID NO:1)
- (ii) HVR-L2 comprising sequence B1-B7, wherein B1-B7 is WASTRES (SEQ ID NO:2)
- (iii) HVR-L3 comprising sequence C1-C9, wherein C1-C9 is QQYYAYPWT (SEQ ID NO:3)
- (iv) HVR-H1 comprising sequence D1-D10, wherein D1-D10 is GYTFTSYWLH (SEQ ID NO:4)
- (v) HVR-H2 comprising sequence E1-E18, wherein E1-E18 is GMIDPSNSDTRFNPNFKD (SEQ ID NO:5)
- (vi) HVR-H3 comprising sequence F1-F11, wherein F1-F11 is XYGSYVSPLDY (SEQ ID NO:6) and X is not R;
- and
- (b) at least one variant HVR, wherein the variant HVR comprises modification of at least one residue of the sequence depicted in SEQ ID NO:
- 1, 2, 3, 4, 5 or 6.
A humanized anti-c-met antibody wherein monovalent affinity of the antibody to human c-met is substantially the same as monovalent affinity of a murine antibody comprising a light chain and heavy chain variable sequence as depicted in FIG. 7 (SEQ ID NO:
- 9 and 10).
A humanized anti-c-met antibody wherein monovalent affinity of the antibody to human c-met is at least 3-fold greater than monovalent affinity of a murine antibody comprising a light chain and heavy chain variable sequence as depicted in FIG. 7 (SEQ ID NO:
- 9 and 10).
A humanized anti-c-met antibody wherein the humanized antibody inhibits binding human hepatocyte growth factor to its receptor better than a reference antibody comprising a chimeric anti-c-met antibody comprising a light chain and heavy chain variable sequence as depicted in FIG. 7 (SEQ ID NO:
- 9 and 10).
A humanized anti-c-met antibody wherein the humanized antibody inhibits human hepatocyte growth factor (HGF) receptor activation better than a reference antibody comprising a chimeric anti-c-met antibody comprising a light chain and heavy chain variable sequence as depicted in FIG. 7 (SEQ ID NO:
- 9 and 10).
A humanized anti-c-met antibody wherein the humanized antibody inhibits c-met-dependent cell proliferation better than a reference antibody comprising a chimeric anti-c-met antibody comprising a light chain and heavy chain variable sequence as depicted in FIG. 7 (SEQ ID NO:
- 9 and 10).
The antibody of the preceding claims, wherein both the humanized antibody and chimeric antibody are monovalent.
The antibody of the preceding claims, wherein both the humanized antibody and chimeric antibody comprise a single Fab region linked to an Fc region.
An antibody comprising a heavy chain variable domain comprising HVR1-HC, HVR2-HC and/or HVR3-HC sequence depicted in FIG. 13 (SEQ ID NO:
- 191-193).
An antibody comprising a light chain variable domain comprising HVR1-LC, HVR2-LC and/or HVR3-LC sequence depicted in FIG. 13 (SEQ ID NO:
- 183-185).
A method of inhibiting c-met activated cell proliferation, said method comprising contacting a cell or tissue with an effective amount of an antibody of any of the preceding claims.
A method of modulating a disease associated with dysregulation of the HGF/c-met signaling axis, said method comprising administering to a subject an effective amount of an antibody of any of the preceding claims.
A method of treating a subject having cancer, said method comprising administering to the subject an effective amount of an antibody of any of the preceding claims.
A method of treating a proliferative disorder in a subject, said method comprising administering to the subject an effective amount of an antibody of any of the preceding claims.
The composition of claim 53, wherein the composition comprises a carrier.
Dependencies are inferred from the claim text.