Human monoclonal antibody binding to hGM-CSF and its antigen binding portion
Inventors
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-7935795-B2
Publication Date
2011-05-03
Expiration Date
Abstract
The present invention provides a human monoclonal antibody, and antigen-binding portions thereof, capable of binding to human granulocyte-macrophage colony stimulating factor (hGM-CSF) and neutralizing the bioactivity of the hGM-CSF, wherein the anti-hGM-CSF monoclonal antibody has a light chain (L chain) including an amino acid sequence SEQ ID NO:1 and a heavy chain (H chain) including an amino acid sequence SEQ ID NO: 2. Also provided are human monoclonal anti-hGM-CSF antibodies, and antigen-binding portions thereof, characterized by complementarity determining regions (CDRs) or H chain and L chain variable regions related to SEQ ID NO:1 and SEQ ID NO:2. Antibodies, and antigen-binding portions thereof, of the invention are useful in the treatment of diseases associated with overproduction of hGM-CSF, including allergic disease, graft rejection and graft-versus-host disease (GVHD), and autoimmune diseases.
Core Innovation
The invention provides a human monoclonal antibody or its antigen binding portion that binds human granulocyte-macrophage colony stimulating factor (hGM-CSF) and neutralizes bioactivity of the hGM-CSF. The antibody is defined by specific light chain and heavy chain complementarity determining region (CDR) domains, including L chain CDR1, CDR2, and CDR3 sequences of SEQ ID NO:5, SEQ ID NO:6, and SEQ ID NO:7, respectively.
For the heavy chain, the H chain CDR1, CDR2, and CDR3 domains are constrained to the amino acid sequences of SEQ ID NO:8, SEQ ID NO:9, and SEQ ID NO:10, respectively. The invention further defines antigen binding portions that include an L chain variable region (LCVR) having the amino acid sequence of SEQ ID NO:3 and an H chain variable region (HCVR) having the amino acid sequence of SEQ ID NO:4.
The document addresses the need for anti-hGM-CSF neutralizing antibodies with defined binding and neutralizing performance. The antibody is described as having affinity for hGM-CSF and neutralizing capacity, including inhibition of proliferation of peripheral blood dendritic cells.
Claims Coverage
The document includes one independent claim, directed to a human monoclonal antibody or its antigen-binding portion with binding and neutralization of hGM-CSF defined by six CDR sequence constraints.
Hgm-csf binding and neutralization by a defined human monoclonal antibody
A human monoclonal antibody or its antigen binding portion capable of binding to human granulocyte-macrophage colony stimulating factor (hGM-CSF) and neutralizing bioactivity of the hGM-CSF, wherein the antibody comprises a light chain CDR 1 domain having the amino acid sequence of SEQ ID NO:5, an L chain CDR 2 domain having the amino acid sequence of SEQ ID NO:6, an L chain CDR 3 domain having the amino acid sequence of SEQ ID NO:7, a heavy chain CDR 1 domain having the amino acid sequence of SEQ ID NO:8, an H chain CDR 2 domain having the amino acid sequence of SEQ ID NO:9, and an H chain CDR 3 domain having the amino acid sequence of SEQ ID NO:10.
Overall claim coverage focuses on an anti-hGM-CSF human monoclonal antibody or antigen-binding portion whose binding and neutralization are defined by the specified L-chain and H-chain CDR sequence constraints.
Stated Advantages
Neutralizing bioactivity of hGM-CSF.
Defined affinity for hGM-CSF, including an affinity range of 2.0×10^-10 M to 2.3×10^-10 M.
Quantified neutralizing capacity at about 2 μg/mL, equivalent to that of a 750- to 1500-fold dilution of patient blood serum from idiopathic alveolar proteinosis.
Inhibition of proliferation of peripheral blood dendritic cells.
Documented Applications
Therapeutic uses of the anti-hGM-CSF monoclonal antibody for allergic diseases, graft rejection, graft-versus-host disease (GVHD), and autoimmune diseases such as rheumatoid arthritis.
Idiopathic alveolar proteinosis is referenced in connection with the neutralizing-capacity equivalence using patient blood serum.
Interested in licensing this patent?