MN/CA IX-SPECIFIC MONOCLONAL ANTIBODIES GENERATED FROM MN/CA IX-DEFICIENT MICE AND METHODS OF USE

摘要

Disclosed herein among other MN/CA IX-related inventions are new MN/CA IX-specific antibodies generated from MN/CA IX-deficient mice, preferably monoclonal antibodies and immunoreactive fragments and engineered variants thereof. Subsets of the new antibodies are to either the proteoglycan-like (PG) domain or to the carbonic anhydrase (CA) domain of MN/CA IX, and methods are provided by which antibodies can be prepared to the other MN/CA IX domains. Such new MN/CA IX-specific antibodies, fragments and variants are useful diagnostically/prognostically and therapeutically for cancer and precancer. Particularly preferred are the new monoclonal antibodies, fragments and variants that are specific for the non-immunodominant epitopes of MN/CA IX, which antibodies are, among other uses, useful to detect soluble MN/CA IX (s-CA IX) in body fluids, alone but preferably in combination with antibodies specific to the immunodominant epitopes of MN/CA IX, for example, in a sandwich assay.

主权项

1. A monoclonal antibody or antigen-binding fragment thereof that specifically binds to a non-immuno dominant epitope of MN//CA IX protein or MN/CA IX polypeptide, wherein said antibody is generated from MN/CA IX-deficient mice and wherein said antibody does not compete for binding to MN/CA IX with monoclonal antibodies MN7, M75 or MN12, with the proviso that the antibody does not bind to the proteoglycan-like (PG) domain of MN/CA IX, and wherein said epitope is selected from epitopes
(a) within the carbonic anhydrase (CA) domain having the amino acid sequence of SEQ ID NO: 9, (b) within the CA domain having the amino acid sequence of SEQ ID NO: 101, (c) within the CA domain having the amino acid sequence of SEQ ID NO: 67, (d) within the CA domain having the amino acid sequence SEQ ID NO: 69, (e) within the transmembrane domain (TM) having the amino acid sequence of SEQ ID NO: 6, and (f) within the intracellular domain (IC) having the amino acid sequence of SEQ ID NO: 7.