Human monoclonal antibodies to FC alpha receptor (CD89)
AssigneeMedarex, Inc.
InventorsDebra Hudson, Marcus A. van Dijk, Jan G. J. van de Winkel
Life of this patent
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Abstract
Human monoclonal antibodies which bind specifically to Fc alpha receptor (CD89), including monoclonal antibodies which react specifically to Fc receptor for IgA of human effector cells are disclosed. The binding agents, e.g., antibodies are useful for targeting human effector cells (e.g. macrophages) against a target cell (e.g. a cancer cell, an infectious agent, etc.). For this purpose, bifunctional antibodies or heteroantibodies can be constructed containing the binding region derived from an anti-Fc-alpha receptor antibody and the binding region of a target-specific antibody. Targeted effector cells can specifically lyse target cells.
Claims16
An isolated human monoclonal antibody, or antigen binding portion thereof, selected from the group consisting of:
- (a) an antibody, or antigen binding portion thereof, comprising (i) a heavy chain variable region comprising CDR1, CDR2, and CDR3 sequences comprising amino acid residues 30–35, amino acid residues 50–66, and amino acid residues 99–108 of SEQ ID NO:2, respectively;
- and (ii) a light chain variable region comprising CDR1, CDR2, and CDR3 sequences comprising amino acid residues 24–34, amino acid residues 50–56, and amino acid residues of 89–97 of SEQ ID NO:4, respectively, wherein the antibody binds to human CD89;
- and
- (b) an antibody, or antigen binding portion thereof, comprising (i) a heavy chain variable region comprising CDR1, CDR2, and CDR3 sequences comprising amino acid residues 31–35, amino acid residues 50–66, and amino acid residues 99–108 of SEQ ID NO:6, respectively;
- and (ii) a light chain variable region comprising CDR1, CDR2, and CDR3 sequences comprising amino acid residues 24–35, amino acid residues 51–57, and amino acid residues 90–99 of SEQ ID NO:8, respectively, wherein the antibody binds to human CD89.
An isolated human monoclonal antibody, or antigen binding portion thereof, comprising a human heavy chain variable region and a human light chain variable region, wherein:
- (a) the human heavy chain variable region comprises the amino acid sequence of SEQ ID NO:2;
- (b) the human light chain variable region comprises the amino acid sequence of SEQ ID NO:4;
- (c) the antibody binds to human CD89;
- (d) the antibody does not activate complement upon binding to CD89 in vivo;
- and
- (e) the antibody does not block IgA binding to CD89.
An isolated human monoclonal antibody, or antigen binding portion thereof, comprising a human heavy chain variable region and a human light chain variable region, wherein:
- (a) the human heavy chain variable region comprises the amino acid sequence of SEQ ID NO:6;
- (b) the human light chain variable region comprises the amino acid sequence of SEQ ID NO:8;
- (c) the antibody binds to human CD89;
- (d) the antibody does not activate complement upon binding to CD89 in vivo;
- and
- (e) the antibody does not block IgA binding to CD89.
An isolated human monoclonal antibody, or antigen binding portion thereof, comprising human heavy chain and human light chain variable regions comprising the amino acid sequences shown in SEQ ID NO:2 and SEQ ID NO:4, respectively.
An isolated human monoclonal antibody, or antigen binding portion thereof, comprising human heavy chain and human light chain variable regions comprising the amino acid sequences shown in SEQ ID NO:6 and SEQ ID NO:8, respectively.
A composition comprising a pharmaceutically acceptable carrier and an isolated human monoclonal antibody, or antigen binding portion thereof, comprising:
- (a) a heavy chain variable region derived from a human germline VH 3–30.3 gene;
- and
- (b) a light chain variable region derived from a human germline VK L18 gene or VK A27 gene;
- wherein the human antibody binds human CD89.
An isolated human monoclonal antibody, or antigen binding portion thereof, comprising:
- (a) a heavy chain variable region derived from a human germline VH3-30.3 gene;
- and
- (b) a light chain variable region is derived from a human germline VK L18 gene;
- wherein the human antibody binds human CD89 and wherein the antibody does not activate complement upon binding to CD89 in vivo.
An isolated human monoclonal antibody, or antigen binding portion thereof, comprising:
- (a) a heavy chain variable region derived from a human germline VH 3-303 gene;
- (b) a light chain variable region derived from a human germline VK A27 gene;
- wherein the human antibody binds human CD89.
Dependencies are inferred from the claim text.