MN/CA IX/CA9 and Renal Cancer Prognosis

• US 7,482,129 B2
• Filed: 05/04/2005
• Issued: 01/27/2009
• Est. Priority Date: 05/04/2004
• Status: Expired due to Fees

• Current Assignee: Bayer Healthcare LLC (Bayer AG), Biomedical Research Centre Of The Slovak Academy Of Sciences
• Original Assignee: Institute of Virology, Slovak Academy of Sciences
• Inventors: Erdo{hacek over (g)}an, Seyda, Soyupak, Bülent
• Primary Examiner(s): Martinell; James
• Application Number:
  US11/578,744
• Publication Number:
  US 20070224606A1
• Time in Patent Office: 1,364 Days
• Field of Search: None
• US Class Current: 435/7.1
• CPC Class Codes: C12Q 1/6886 for cancer immunoassay for cancer G01N33/574
• CPC Class Codes: C12Q 2600/106 Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
• CPC Class Codes: C12Q 2600/112 Disease subtyping, staging or classification
• CPC Class Codes: C12Q 2600/118 Prognosis of disease development
• CPC Class Codes: C12Q 2600/158 Expression markers
• CPC Class Codes: G01N 33/57438 of liver, pancreas or kidney

Abstract

Herein disclosed are methods that are prognostic for renal cell carcinoma, particularly renal clear cell carcinoma, afflicting a vertebrate. An exemplary prognostic method comprises detecting the presence of, and quantitating the level and/or extent of a MN/CA9 gene expression product in a sample from the affected subject, wherein if 50% or fewer cells are found to express the MN/CA9 gene, then the subject is considered to have a poorer prognosis. MN/CA9 gene expression products useful in the prognostic methods include MN protein, MN polypeptide and/or MN nucleic acids. The methods are useful as an aid in the selection of treatment for a patient with renal cell carcinoma, alone or in combination with conventional tumor stage and/or grade information. The methods of the invention can be used, for example, to identify those patients requiring more aggressive therapy regimens, or those patients most likely to respond to adjuvant immunotherapies, particularly MN/CA IX/CA9-targeted therapies.

Claims

1. A method which is prognostic for renal cell carcinoma afflicting a vertebrate, said method comprising:

(a) detecting the presence or absence of MN/CA IX protein or MN/CA IX polypeptide in a sample comprising neoplastic cells taken from said vertebrate, comprising immunologically assaying said sample with the M75 monoclonal antibody secreted by hybridoma VU-M75 which has Accession No. ATCC HB 11128,

(b) if MN/CA IX protein or MN/CA IX polypeptide is present in said sample, quantitating the level and/or extent of said MN/CA IX protein or MN/CA IX polypeptide relative to the number of cells in said sample, and

(c) determining that said vertebrate has a prognosis of shorter cumulative survival if the level and/or extent of MN/CA IX protein or MN/CA IX polypeptide of steps (a) and (b) indicates that 50% or fewer of cells in said sample express MN/CA IX protein or MN/CA IX polypeptide;

wherein said MN/CA IX protein or MN/CA IX polypeptide is encoded by a nucleotide sequence selected from the group consisting of;

(1) SEQ ID NO;

1'"'"'s coding region;

(2) nucleotide sequences that hybridize under stringent hybridization conditions of 50% formamide at 42 degree C. to complement of SEQ ID NO;

1'"'"'s coding region; and

(3) nucleotide sequences that differ from SEQ ID NO;

1'"'"'s coding region or from the nucleotide sequences of (2) in codon sequence due to the degeneracy of the genetic code;

and wherein said MN/CA IX protein or said MN/CA IX polypeptide is specifically bound by the M75 monoclonal antibody that is secreted from the hybridoma VU-M75 which has Accession No. ATCC HB 11128.