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US 5,789,554 AGranted
Immunoconjugates and humanized antibodies specific for B-cell lymphoma and leukemia cells
AssigneeImmunomedics, Inc.
InventorsShui-on Leung, Hans Hansen
Life of this patent
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AssigneeImmunomedics, Inc.
InventorsShui-on Leung, Hans Hansen
Estimating the term…
A chimeric LL2 monoclonal antibody is described in which the complementarity determining regions (CDRs) of the light and heavy chains of the murine LL2 anti-B-lymphoma, anti-leukemia cell monoclonal antibody has been recombinantly joined to the human kappa and IgG.sub.1 constant region domains, respectively, which retains the immunospecificity and B-cell lymphoma and leukemia cell internalization capacity of the parental murine LL2 monoclonal antibody, and which has the potential of exhibiting reduced human anti-mouse antibody production activity. A humanized LL2 monoclonal antibody is described in which the CDRs of the light and heavy chains have been recombinantly joined to a framework sequence of human light and heavy chains variable regions, respectively, and subsequently linked to human kappa and IgG.sub.1 constant region domains, respectively, which retains the immunospecificity and B-lymphoma and leukemia cell internalization capacities of the parental murine and chimeric LL2 monoclonal antibodies, and which has the potential for exhibiting reduced human anti-mouse antibody production activity. Vectors for producing recombinant chimeric and humanized chimeric monoclonal antibodies are provided. Isolated DNAs encoding the amino acid sequences of the LL2 variable light and heavy chain and CDR framework regions are described. Conjugates of chimeric and humanized chimeric LL2 antibodies with cytotoxic agents or labels find use in therapy and diagnosis of B-cell lymphomas and leukemias.
A humanized LL2 (hLL2) monoclonal antibody, (mAb), designated hLL2-2, comprising the complementarity-determining regions (CDRs) of mouse LL2 (mLL2), wherein said hLL2-2 mAb retains substantially the B-lymphoma cell and leukemia cell targeting and cell internalization characteristics of said mLL2 mAb, and wherein said hLL2-2 mAb is less immunogenic in a human subject than is said mLL2 mAb, and wherein said hLL2-2 mAb comprises the heavy chain variable region of SEQ ID NO:
A humanized LL2 (hLL2) monoclonal antibody, (mAb), designated hLL2-1, comprising the complementarity-determining regions (CDRs) of mouse LL2 (mLL2), wherein said hLL2-1 mAb retains substantially the B-lymphoma cell and leukemia cell targeting and cell internalization characteristics of said mLL2 mAb, and wherein said hLL2-1 mAb is less immunogenic in a human subject than is said mLL2 mAb, and wherein said hLL2-1 mAb comprises the heavy chain variable region of SEQ ID NO:
An expression vector comprising a DNA sequence encoding the humanized hLL2-2 heavy chain variable region of SEQ ID NO:
The humanized LL2-2 heavy chain variable region of SEQ ID NO:
An expression vector comprising a DNA sequence encoding the humanized hLL2 light chain variable region of SEQ ID NO:
The humanized LL2 light chain variable region of SEQ ID NO:
An expression vector comprising a DNA sequence encoding the humanized hLL2-1 heavy chain variable region of SEQ ID NO:
The humanized LL2-1 heavy chain variable region of SEQ ID NO:9.
Dependencies are inferred from the claim text.