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US 9,433,687 B2Granted
Anti-Notch3 antibodies and antibody-drug conjugates
AssigneePfizer Inc.
InventorsKenneth G. Geles, Yijie Gao, Puja Sapra, Lioudmila Gennadievna Tchistiakova, Bin-Bing Stephen Zhou
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Abstract
The present invention provides for anti-Notch3 antibodies, anti-Notch3 antibody-drug conjugates and methods for preparing and using the same.
Claims64
An isolated antibody, or antigen-binding fragment thereof, that binds to Notch3 comprising:
- a VH CDR1, a VH CDR2, and a VH CDR3 of a heavy chain variable region (VH) comprising the amino acid sequence set forth in SEQ ID NO:
- 13;
- and
- a VL CDR1, a VL CDR2, and a VL CDR3 of a light chain variable region (VL) comprising the amino acid sequence set forth in SEQ ID NO:
- 25.
2 more elements
An isolated antibody, or antigen-binding fragment thereof, that binds to Notch3 comprising:
- a VH CDR1, a VH CDR2, and a VH CDR3 of a heavy chain variable region (VH) comprising the amino acid sequence set forth in SEQ ID NO:
- 37;
- and
- a VL CDR1, a VL CDR2, and a VL CDR3 of a light chain variable region (VL) comprising the amino acid sequence set forth in SEQ ID NO:
- 49.
2 more elements
An antibody-drug conjugate of the formula:
- Ab-(L-D)p,
- wherein:
- (a) Ab is an antibody, or antigen-binding fragment thereof, that binds to Notch3;
- (b) L-D is a linker-drug moiety, wherein L is a linker selected from the group consisting of maleimidocaproyl-valine-citrulline-p-aminobenzyloxycarbonyl (vc), maleimidocaproyl (mc), maleimido-heptanoyl (me) and maleimido-Peg6C2 (MalPeg6C2) and D is a drug selected from the group consisting of:
- (i) 0101 having the formula:
- (ii) 6780 having the formula:
- (iii) 0131 having the formula:
- (iv) 3377 having the formula:
- and
- (v) 8261 having the formula:
- and
- (c) p is an integer from 1 to 12.
9 more elements
An antibody-drug conjugate of the formula:
- Ab-(L-D)p,
- wherein:
- (a) Ab is an antibody, or antigen-binding fragment thereof, that binds to Notch3,
- (b) L-D is a linker-drug moiety, wherein L is a linker and D is a drug, wherein L-D is selected from the group consisting of:
- vc0101 having the formula:
- and vc6780 having the formula:
- and
- (c) p is an integer from 1 to 12.
5 more elements
An antibody-drug conjugate of the formula:
- Ab-(L-D)p,
- wherein:
- (a) Ab is an antibody, or antigen-binding fragment thereof, that binds to Notch3 comprising a VH CDR1, a VH CDR2 and a VH CDR3 of a heavy chain variable region (VH) comprising the amino acid sequence set forth in SEQ ID NO:
- 13 and a VL CDR1, a VL CDR2 and VL CDR3 of a light chain variable region (VL) comprising the amino acid sequence set forth in SEQ ID NO:
- 25;
- (b) L-D is a linker-drug moiety, wherein L is a linker, and D is a drug;
- and
- (c) p is an integer from 1 to 12.
5 more elements
An antibody-drug conjugate of the formula:
- Ab-(L-D)p,
- wherein:
- (a) Ab is an antibody, or antigen-binding fragment thereof, that binds to Notch3 comprising a VH CDR1, a VH CDR2, and a VH CDR3 of a heavy chain variable region (VH) comprising the amino acid sequence set forth in SEQ ID NO:
- 37;
- and a VL CDR1, a VL CDR2, and a VL CDR3 of a light chain variable region (VL) comprising the amino acid sequence set forth in SEQ ID NO:
- 49;
- (b) L-D is a linker-drug moiety, wherein L is a linker, and D is a drug;
- and
- (c) p is an integer from 1 to 12.
6 more elements
An antibody-drug conjugate of the formula:
- Ab-(L-D)p,
- wherein:
- (a) Ab is an antibody, or antigen-binding fragment thereof, comprising a heavy chain variable region amino acid sequence of SEQ ID NO:
- 13 and a light chain variable region amino acid sequence of SEQ ID NO 25;
- (b) L-D is a linker-drug moiety, wherein L is a linker, and D is a drug, wherein the L-D is vc0101 having the formula
- and
- (c) p is an integer from 1 to 12.
4 more elements
Dependencies are inferred from the claim text.