Humanized immunoglobulin reactive with b7-2 and methods of treatment therewith

A humanized immunoglobulin having binding specificity for B7-2, comprising a constant region of human origin and an antigen binding region, wherein said antigen binding region comprises:

• a) a complementarity determining region derived from an antibody of rodent origin that binds to B7-2, and
• b) a framework region derived from human origin.

A humanized immunoglobulin having binding specificity for B7-2 derived from the cell line deposited with the ATCC, Accession No. CRL-12524.

A humanized immunoglobulin having a binding specificity for B7-2 comprising a heavy chain and a light chain,

• the light chain comprising a complementarity determining region derived from an antibody of nonhuman origin which binds B7-2 and a framework region derived from a light chain of human origin, and
• the heavy chain comprising a complementarity determining region derived from an antibody of nonhuman origin which binds B7-2 and a framework region derived from a heavy chain of human origin.

A humanized immunoglobulin light chain having binding specificity for B7-2 comprising CDR1, CDR2 and CDR3 of the light chain of murine 3D1 antibody, and a human light chain framework region.

A humanized immunoglobulin heavy chain specific for B7-2 comprising CDR1, CDR2 and CDR3 of the heavy chain of the 3D1 antibody, and a human heavy chain framework region.

A humanized immunoglobulin which specifically binds to B7-2 comprising:

• a) a humanized light chain comprising three light chain complementarity determining regions from the mouse 3D1 antibody and a light chain variable region framework sequence from a human immunoglobulin light chain, and
• b) a humanized heavy chain comprising three light chain complementarity determining regions from the mouse 3D1 antibody and a heavy chain variable region framework sequence from a human immunoglobulin heavy chain.

An expression vector comprising a fused gene encoding a humanized immunoglobulin light chain, said gene comprising a nucleotide sequence encoding a CDR derived from a light chain of a nonhuman antibody having binding specificity for B7-2 and a framework region derived from a light chain of human origin.

An expression vector comprising a fused gene encoding a humanized immunoglobulin heavy chain, said gene comprising a nucleotide sequence encoding a CDR derived from a heavy chain of a nonhuman antibody having binding specificity for B7-2 and a framework region derived from a heavy chain of human origin.

A host cell comprising a first recombinant nucleic acid encoding a humanized immunoglobulin light chain and a second recombinant nucleic acid encoding a humanized immunoglobulin heavy chain, said first nucleic acid comprising a nucleotide sequence encoding a CDR derived from the light chain of murine 3D1 antibody and a framework region derived from a light chain of human origin;

• and said second nucleic acid comprising a nucleotide sequence encoding a CDR derived from the heavy chain of murine 3D1 antibody and a framework region derived from a heavy chain of human origin.

A fused gene encoding a humanized immunoglobulin light or heavy chain comprising:

• a) a first nucleic acid sequence encoding an antigen binding region derived from murine 3D1 monoclonal antibody;
• and
• b) a second nucleic acid sequence encoding at least a portion of a constant region of an immunoglobulin of human origin.

A method of treating a patient with a disease selected from the group consisting of:

• autoimmune diseases, infectious diseases, inflammatory disorders, systemic lupus erythematosus, diabetes mellitus, insulitis, arthritis, inflammatory bowel disease, inflammatory dermatitis, and multiple sclerosis, comprising administering a therapeutically effective amount of a humanized immunoglobulin specific to B7-2 to the patient.

A method for determining the presence or absence of B7-2 in a sample comprising the steps of:

• a) contacting said sample with a humanized antibody specific to B7-2 sufficiently to allow formation of a complex between B7-2 and the anti-B7-2 antibody, and
• b) detecting the presence or absence of said complex formation.

A method for treating a patient with a disease selected from the group consisting of:

• autoimmune diseases, infectious diseases, inflammatory disorders, systemic lupus erythematosus, diabetes mellitus, insulitis, asthma, arthritis, inflammatory bowel disease, inflammatory dermatitis, and multiple sclerosis, comprising administering a therapeutically effective amounts of a humanized immunoglobulin specific to B7-1 and a therapeutically effective amount of a humanized immunoglobulin specific to B7-2.

A method of modulating an immune response of a patient having a transplanted organ, tissue, cell or the like comprising administering an effective amount of the humanized immunoglobulin specific to B7-1 and an effective amount of a humanized immunoglobulin specific to B7-2 in a carrier.

A method for transplanting cells to a patient in need thereof, comprising:

• a) obtaining cells from a donor,
• b) contacting the cells with an immunoglobulin specific to B7-1, an immunoglobulin specific to B7-2 and recipient cells from the patient for a period of time sufficient for tolerance induction, thereby obtaining a mixture, and
• c) introducing the mixture to the patient.

A method for transplanting cells to a patient in need thereof, comprising:

• a) obtaining cells from a donor,
• b) contacting the cells with an immunoglobulin specific to B7-1, an immunoglobulin specific to B7-2, and tissue, organ or cells that express MHC Class I antigen, B7-1 and B7-2 molecules, for a period of time sufficient for tolerance induction, thereby obtaining a mixture, and
• c) introducing the mixture to the patient.