Cd70 antibody drug conjugates and methods of using the same
AssigneeGenmab A/S
InventorsXiao SHANG, Haidong LIU, Julia GAVRILYUK, Baiteng ZHAO, Tae HAN, Zhu CHEN
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Abstract
The present invention provides conjugates of CD70 antibodies, and/or antigen binding portions thereof, for use in the treatment of cancer and autoimmune disease.
Claims41
A conjugate comprising:
- a Binding unit bound to one or more Drug units by one or more Linkers, wherein the Binding unit includes at least a portion of an anti-CD70 antibody.
(canceled)
A conjugate comprising:
- a Binding unit bound to one or more Drug units by one or more Linkers, wherein:
- (1) the Binding unit comprises a heavy chain variable (VH) region and a light chain variable (VL) region, the VH region comprising complementarity determining regions HCDR1, HCDR2 and HCDR3 disposed in heavy chain variable region framework regions and the VL region comprising LCDR1, LCDR2 and LCDR3 disposed in light chain variable region framework regions, the VH and VL CDRs having amino acids sequences selected from the sets of amino acid sequences set forth in the group consisting of:
- a. SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:13, SEQ ID NO:24, SEQ ID NO:25 and SEQ ID NO:26, respectively;
- b. SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:14, SEQ ID NO:24, SEQ ID NO:25 and SEQ ID NO:26, respectively;
- c. SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:15, SEQ ID NO:24, SEQ ID NO:25 and SEQ ID NO:26, respectively;
- d. SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25 and SEQ ID NO:18, respectively;
- and
- e. SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25 and SEQ ID NO:26;
- respectively;
- (2) each Linker has the following formula (I):
- or a salt thereof, wherein:
- L1 is a Stretcher unit covalently bound to the Binding unit, wherein the wavy (˜) line indicates an attachment site for the Binding unit;
- AA is an Amino Acid unit having from 1 to 12 subunits;
- s is 0 or 1;
- L2 is a Linker Subunit having from 1 to 4 attachment sites for a Drug unit, wherein the double wavy (≈) line indicates an attachment site for the Drug Unit;
- and
- wherein at least one Polar unit is present within the Amino Acid unit, the Linker Subunit, the Stretcher unit, or combinations thereof, and wherein the Polar unit(s) is selected from Sugar units, PEG units, Carboxyl units, and combinations thereof;
- and
- (3) each Drug unit is covalently attached to each Linker Subunit at (≈).
8-9. (canceled)
(canceled)
19-46. (canceled)
49-70. (canceled)
74-79. (canceled)
The conjugate of claim 79, wherein the cleavable peptide comprises a Lys(PEG)-valine-citrulline peptide, a valine-Cit(PEG) peptide, a Lys(PEG)-valine-lysine peptide, a valine-lysine(PEG) peptide, a Lys(PEG)-valine-alanine peptide, a Lys(PEG)-phenylalanine-lysine peptide, a phenylalanine-Lys(PEG)) peptide or a Lys(PEG)-glycine-glycine-phenylalanine-glycine peptide, wherein Lys(PEG) and Cit(PEG) comprise a PEG unit attached to a lysine residue or a citrulline residue, respectively.
82-87. (canceled)
(canceled)
92-95. (canceled)
The conjugate of claim 95, wherein the cytotoxic agent is exatecan.
97-117. (canceled)
123-153. (canceled)
Dependencies are inferred from the claim text.