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US 11,999,787 B2Granted
Tie2-binding agents and methods of use
AssigneeGenentech, Inc.
InventorsMinhong Yan, Gu Zhang, Nicholas John Agard, Danielle Marie Dicara, Philip E. Hass, Julie Q. Hang, Erin L. Christensen, Robert Paul Morse, Sarah Sanowar, Vittal Shivva
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Abstract
The invention provides Tie-2 antibodies and fragments thereof and conjugates and methods of using the same.
Claims30
A conjugate that binds to Tie2, wherein the conjugate comprises two, three, four, five, six, seven, or eight antibodies or antigen-binding fragments thereof, wherein each of the antibodies or fragments thereof bind Tie2 and comprises:
- a heavy chain variable domain (VH) comprising (a) CDR-H1 comprising the amino acid sequence NTDIS (SEQ ID NO:3), (b) CDR-H2 comprising the amino acid sequence RISPSDGNTYYADSVKG (SEQ ID NO:4), and (c) CDR-H3 comprising the amino acid sequence RTRWASWAFDY (SEQ ID NO:7), and a light chain variable domain (VL) comprising (d) CDR-L1 comprising the amino acid sequence RASQDVSTAVA (SEQ ID NO:8), (e) CDR-L2 comprising the amino acid sequence SASFLYS (SEQ ID NO:9), and (f) CDR-L3 comprising the amino acid sequence QQSYTTPPT (SEQ ID NO:10), and
- wherein each of the antibodies or antigen-binding fragment thereof is linked to a multimerizing moiety.
A conjugate which binds Tie2 comprising:
- a Fab comprising a heavy chain (HC) having SEQ ID NO:55 and a light chain (LC) having SEQ ID NO:25;
- conjugated to a polyol which has the structure of Formula 1 (b)
- wherein each m is independently an integer from 10-30, wherein R1 and R2 taken together has the structure
- wherein R2 is a maleamide;
- and
- wherein the polyol is linked to the Fab HC at residue C209 (EU numbering).
3 more elements
A conjugate that binds to Tie2,
- wherein the conjugate comprises six Fabs that bind Tie2, wherein each of the six Fabs comprises:
- a heavy chain variable domain (VH) comprising (a) CDR-H1 comprising the amino acid sequence NTDIS (SEQ ID NO:3), (b) CDR-H2 comprising the amino acid sequence RISPSDGNTYYADSVKG (SEQ ID NO:4), and (c) CDR-H3 comprising the amino acid sequence RTRWASWAFDY (SEQ ID NO:7), and a light chain variable domain (VL) comprising (d) CDR-L1 comprising the amino acid sequence RASQDVSTAVA (SEQ ID NO:8), (e) CDR-L2 comprising the amino acid sequence SASFLYS (SEQ ID NO:9), and (f) CDR-L3 comprising the amino acid sequence QQSYTTPPT (SEQ ID NO:10), and
- wherein each of the Fabs is linked to an arm of a hexameric polyethylene glycol (PEG) molecule.
A conjugate that binds to Tie2,
- wherein the conjugate comprises six Fabs that bind Tie2,
- wherein each of the six Fabs comprises a Fab heavy chain (HC) comprising the sequence of SEQ ID NO:
- 55 and a Fab light chain (LC) comprising the sequence of SEQ ID NO:
- 25,
- wherein each of the six Fabs is linked to an arm of a hexameric polyethylene glycol (PEG) molecule, wherein the hexameric PEG molecule has the structure of general formula (Ib):
- wherein each m is independently an integer from 10-30, wherein R1 and R2 when taken together has the structure
- wherein i and j are 2,
- wherein R2 is a maleamide and is covalently linked to one of the six Fabs through a free sulfhydryl group of engineered cysteine amino acid T209C of the Fab HC (EU numbering).
5 more elements
Dependencies are inferred from the claim text.