Use of inhibitors for the treatment of disorders related to RTK hyperfunction, especially cancer

• US 6,770,742 B1
• Filed: 09/07/2000
• Issued: 08/03/2004
• Est. Priority Date: 01/22/1998
• Status: Expired due to Fees

• Current Assignee: Max-Planck-Gesellschaft Zur Foerderung Der Wissenschaften e.V. (Max-Planck-Gesellschaft zur Frderung der Wissenschaften e)
• Original Assignee: Max-Planck-Gesellschaft Zur Foerderung Der Wissenschaften e.V. (Max-Planck-Gesellschaft zur Frderung der Wissenschaften e)
• Inventors: Ullrich, Axel, Knyazev, Pjotr, Bange, Johannes
• Primary Examiner(s): Eyler, Yvonne
• Assistant Examiner(s): Murphy, Joseph F.
• Application Number:
  US09/600,826
• Time in Patent Office: 1,426 Days
• Field of Search: 530/350, 435/69.1, 435/320.1, 435/325
• US Class Current: 530/350
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/04 specific for metastasis
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 14/71 for growth factors; for growth regulators
• CPC Class Codes: G01N 33/574 for cancer

Abstract

The present invention concerns the use of inhibitors for the treatment and/or prophylaxis of diseases which are the consequence of increased receptor tyrosine kinase activity, particularly cancer. The use is particularly directed towards inhibition or lowering of the overexpression and/or altered activity of receptor tyrosine kinases (RTKs). In particular, this altered activity of receptor tyrosine kinase can be triggered by a mutation of FGFR-4, wherein this mutation is in particular a point mutation in the transmembrane domain of FGFR-4 and leads to an exchange of a hydrophobic amino acid for a hydrophilic amino acid. The invention further concerns the use of an inhibitor directed against FGFR-4, for the treatment and/or prophylaxis of cancer. Furthermore, the invention concerns a mutated FGFR-4, which leads to overexpression and/or altered activity in cells. Finally, the invention concerns a DNA and RNA sequence of a mutated FGFR-4 molecule. Finally, in addition the invention concerns a pharmaceutical composition, containing the inhibitor as described above and further a diagnostic and screening procedure.

Claims

1. An isolated or purified mutated human fibroblast growth factor receptor-4 (FGFR-4), which comprises a point mutation in amino acid 388 of the wild-type human FGFR-4 having the amino acid sequence encoded by the nucleotide sequence of GenBank accession number X57205, wherein the point mutation results in replacement of glycine with arginine, and wherein the isolated and purified mutated human FGFR-4 is characterized by overexpression in a human cell as compared to the wild-type human FGFR-4 having the amino acid sequence encoded by the nucleotide sequence of GenBank accession number X57205 and/or tyrosine kinase activity in a human cell, which differs from the tyrosine kinase activity of the wild-type human FGFR-4 having the amino acid sequence encoded by the nucleotide sequence of GenBank accession number X57205.