Reversal binding agents for anti-factor XI/XIa antibodies and uses thereof
AssigneeNovartis AG
InventorsStefan Ewert, Yasser Khder, Alexander Koch
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Abstract
The present disclosure relates to reversal agents, which specifically bind to anti-Factor XI and/or anti-Factor XIa antibodies, and reverse one or more anticoagulant effects of the anti-Factor XI and/or anti-Factor XIa antibodies, as well as to methods of use thereof, such as methods for reversing anticoagulant effects of such anti-Factor XI and/or anti-Factor XIa antibodies, and to related methods for managing bleeding or bleeding risks.
Claims17
A binding agent which specifically binds a target antibody that binds human Factor XI (FXI) and/or Factor XIa (FXIa) within the catalytic domain, wherein the target antibody comprises (i) a heavy chain variable region (VH) comprising complementarity determining regions HCDR1, HCDR2 and HCDR3 of a VH comprising the amino acid sequence of SEQ ID NO:
- 12 and (ii) a light chain variable region (VL) comprising complementarity determining regions LCDR1, LCDR2, and LCDR3 of a VL comprising the amino acid sequence of SEQ ID NO:
- 23,
- and wherein the binding agent is an antibody or antigen-binding fragment wherein:
- a) the HCDR1 comprises the amino acid sequence of SEQ ID NO:
- 91, the HCDR2 comprises the amino acid sequence of SEQ ID NO:
- 92, the HCDR3 comprises the amino acid sequence of SEQ ID NO:
- 93, the LCDR1 comprises the amino acid sequence of SEQ ID NO:
- 107, the LCDR2 comprises the amino acid sequence of SEQ ID NO:
- 108, and the LCDR3 comprises the amino acid sequence of SEQ ID NO:
- 109;
- b) the HCDR1 comprises the amino acid sequence of SEQ ID NO:
- 94, the HCDR2 comprises the amino acid sequence of SEQ ID NO:
- 95, the HCDR3 comprises the amino acid sequence of SEQ ID NO:
- 96, the LCDR1 comprises the amino acid sequence of SEQ ID NO:
- 110, the LCDR2 comprises the amino acid sequence of SEQ ID NO:
- 111, and the LCDR3 comprises the amino acid sequence of SEQ ID NO:
- 112;
- c) the HCDR1 comprises the amino acid sequence of SEQ ID NO:
- 97, the HCDR2 comprises the amino acid sequence of SEQ ID NO:
- 98, the HCDR3 comprises the amino acid sequence of SEQ ID NO:
- 99, the LCDR1 comprises the amino acid sequence of SEQ ID NO:
- 113, the LCDR2 comprises the amino acid sequence of SEQ ID NO:
- 114, and the LCDR3 comprises the amino acid sequence of SEQ ID NO:
- 115;
- or
- d) the HCDR1 comprises the amino acid sequence of SEQ ID NO:
- 100, the HCDR2 comprises the amino acid sequence of SEQ ID NO:
- 101, the HCDR3 comprises the amino acid sequence of SEQ ID NO:
- 102, the LCDR1 comprises the amino acid sequence of SEQ ID NO:
- 116, the LCDR2 comprises the amino acid sequence of SEQ ID NO:
- 117, and the LCDR3 comprises the amino acid sequence of SEQ ID NO:
- 118.
Dependencies are inferred from the claim text.