C - Chemistry – Metallurgy – 07 – K
Patent
C - Chemistry, Metallurgy
07
K
C07K 16/40 (2006.01) A61K 39/395 (2006.01) C07K 16/42 (2006.01) C12N 5/16 (2006.01) G01N 33/573 (2006.01) G01N 33/574 (2006.01)
Patent
CA 2704273
Disclosed herein is the discovery of a soluble MN/CA IX (s-CA IX) in body fluids, such as, urine and serum. Said s-CA IX comprises the extracellular domain of CA IX or portions thereof. The predominant s-CA IX species is the extracellular domain comprising a proteoglycan-like (PG) domain and carbonic anhydrase (CA) domain, and having a molecular weight of about 50/54 kilodaltons (kd) upon Western blot. A smaller s-CA IX form of about 20 to about 30 kd comprising the CA domain or parts thereof, not linked to the PG domain, has also been found in body fluids. Diagnostic/prognostic methods for precancer and cancer that detect or detect and quantitate said s-CA IX in body fluids, are described. Also disclosed herein is the coexpression of CA IX and HER-2/neu/c-erbB-2 that provides parallel, alternative and potentially synergistic diagnostic/prognostic and therapeutic strategies for precancer and cancer. Further disclosed are new MN/CA IX-specific antibodies generated from MN/CA IX-deficient mice, preferably monoclonal antibodies and immunoreactive fragments and engineered variants thereof. 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 immunodiminant epitopes of MN/CA IX, for example, in a sandwich assay.
Ortova Gut Marta
Pastorek Jaromir
Pastorekova Silvia
Zatovicova Miriam
Zavada Jan
Institute Of Virology
Ridout & Maybee Llp
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