Anti-nkg2a antibodies and uses thereof
OwnerPetrus Johannes Louis Spee, Soeren Berg Padkaerinventors
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Abstract
Described herein are anti-NKG2A antibodies suitable for human therapy, including humanized versions of murine anti-NKG2A antibody Z270, as well as related methods and materials for producing and using such antibodies. Exemplary complementarity-determining regions (CDRs) sequences and sites for optional amino acid back-substitutions in framework region (FR) and/or CDRs of such antibodies are also described.
Claims20
An isolated antibody that specifically binds NKG2A, comprising antigen-binding residues from the complementarity-determining regions (CDRs) of murine antibody Z270 and human acceptor framework sequences, wherein said antibody comprises a VL domain that is at least 90% identical to SEQ ID NO:
- 4 and a VH domain that is at least 90% identical to SEQ ID NO:
- 5, and wherein said antibody is more effective than an antibody comprising murine antibody Z270 variable light (VL) (SEQ ID NO:
- 1) and VH (SEQ ID NO:
- 2) sequences in potentiating the cytotoxic activity of a CD94/NKG2A-expressing cytotoxic lymphocyte.
An isolated antibody that specifically binds NKG2A, comprising:
- a CDR-L1 corresponding to residues 24-34 of SEQ ID NO:
- 4;
- a CDR-L2 corresponding to residues 50-56 of SEQ ID NO:
- 4;
- a CDR-L3 corresponding to residues 89-97 of SEQ ID NO:
- 4;
- a CDR-H1 corresponding to residues 31-35 of SEQ ID NO:
- 5;
- a CDR-H3 corresponding to residues 95-102 of SEQ ID NO:
- 5;
- and
- a CDR-H2 comprising residues 50-59 of SEQ ID NO:
- 5;
- and
- human acceptor framework sequences;
- wherein residues 60-65 in the CDR-H2 are from a VH human acceptor sequence, and
- wherein the humanized antibody is more effective than an antibody comprising a variable light (VL) sequence corresponding to SEQ ID NO:
- 1 and a VH sequences corresponding to SEQ ID NO:
- 2 in potentiating the cytotoxic activity of a CD94/NKG2A-expressing NK cell, wherein the residue numbering is referenced with respect to Kabat numbering.
An isolated antibody that specifically binds NKG2A, the antibody comprising a VH domain that comprises non-human CDR residues and human VH acceptor framework sequences, the VH domain comprising a CDR-H1 corresponding to residues 31-35 of SEQ ID NO:
- 5, a CDR-H2 corresponding to residues 50-65 of SEQ ID NO:
- 5, and a CDR-H3 corresponding to residues 95-102 of SEQ ID NO:
- 5, wherein the residue numbering is referenced with respect to Kabat numbering.
Dependencies are inferred from the claim text.