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Antibodes specific for CD44V6

A technology of antibodies and antibody molecules, applied in the field of oncology, can solve problems such as poor affinity CDR-grafted antibodies, which cannot be regarded as useful

Inactive Publication Date: 2004-10-27
BOEHRINGER INGELHEIM INT GMBH +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Therefore, CDR-grafted antibodies with poor binding affinity cannot be considered therapeutically useful

Method used

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  • Antibodes specific for CD44V6
  • Antibodes specific for CD44V6
  • Antibodes specific for CD44V6

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0147] Embodiment 1 radioimmunotherapy

[0148] Materials and methods

[0149] Monoclonal antibodies. mMAb BIWA 1=VFF 18 (secreted by a hybridoma cell line, deposited at DSM-Deutsche Sammlung furMikroorganismen und Zellkulturen GmbH, Mascheroder Weg 1b, D-38124 Braunschweig, Deutschland on June 7, 1994 under accession number DSM ACC2174; see also WO 95 / 33771) was produced by immunizing BALB / c mice with a glutathione S-transferase fusion protein containing human CD44 domain v3-v10 (Heider et al., 1996). The epitope recognized by BIWA 1 has been assigned to amino acids 360-370 in CD44 domain Vb (numbering according to Kugelman et al. (1992)). The batch used in this study was obtained after protein-G Sepharose purification and dialysis against PBS.

[0150] MAb U36 (IgG1) was derived after immunization of mice with the HNSCC cell line UM-SCC-22B and recognizes a different epitope in CD44v6 than that recognized by BIWA 1. U36 was purified from concentrated tissue culture super...

example 2

[0215] Example 2 sequence details

[0216] This example shows the detailed sequence, such as the location of the cloning site, leader sequence and untranslated regions.

[0217] abbreviation:

[0218] aa = amino acid

[0219] nt = nucleotide sequence

[0220] SEQ ID No.1 VH BIWA 4 / 8aa

[0221] EVQLVESGGGLVKPGGSLRLSCAASGFTFSSYDMSWVRQAPGKGLEWVSTISSGGSY

[0222] TYYLDSIKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARQGLDYWGRGTLVTVSS

[0223] SEQ ID No.2 VL BIWA 4aa

[0224] EIVLTQSPATLSSLSPGERATLSCSASSSINYIYWYQQKPGQAPRLLIYLTSNLASGVPAR

[0225] FSGSGSGTDFTLTISSLEPEDFAVYYCLQWSSNPLTFGGGTKVEIK

[0226] SEQ ID No.3 VL BIWA 8aa

[0227] EIVLTQSPATLSSLSPGERATLSCSASSSINYIYWLQQKPGQAPRILIYLTSNLASGVPARF

[0228] SGSGSGTDFTLTISSLEPEDFAVYYCLQWSSNPLTFGGGTKVEIK

[0229] SEQ ID No.4 VH BIWA 4 / 8nt

[0230] GAAGTGCAGCTGGTGGAGTCTGGGGGAGGCTTAGTGAAGCCTGGAGGGTCCCTAAGACTCTCC

[0231] TGTGCAGCCTCTGGATTCACTTTCAGTAGCTATGACATGTCTTGGGTTCGCCAGGCTCCGGGG

[0232] AAGGGGCTGGAGTGGGTCTCAAACCATTAGTAGTGGTGGTAGTTACAC...

example 3

[0698] Example 3 Clinical Research 1170.1

[0699] 1. List of term abbreviations and definitions

[0700] ADCC antibody-dependent cell-mediated cytotoxicity

[0701] Adverse effects of AEs

[0702] ALT alanine aminotransferase

[0703] a.p.

[0704] AP alkaline phosphatase

[0705] AST aspartate aminotransferase

[0706] AUC is the area under the concentration-time curve

[0707] Bq Becquerel, radioactive Becquerel

[0708] SI unit (1Bq = one decay / second)

[0709] BSA bovine serum albumin

[0710] CD44v6 CD44 variant isoform v6

[0711] CDS Common Drug Safety (Corporate Drug Safety)

[0712] Centi Gray detection of cGy versus radioactivity

[0713] CHO Chinese Hamster Ovary Cells

[0714] Ci Curie; unit of radioactivity; 1 Curie=37×10 9 Decay / s

[0715] =37GBq

[0716] CL total body clearance

[0717] cMAb chimeric monoclonal antibody

[0718] cm cm

[0719] C max Maximum Drug Concentration Observed

[0720] cpm counts ...

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Abstract

The present invention belongs to the field of oncology. The invention relates to antibodies with specified sequence which are specific for an epitope which is coded by the variant exon v6 of the CD44 gene and to derivatives of said antibody. The invention also provides nucleic acid molecules encoding said antibody proteins. The invention furthermore pertains to methods for producing said antibody proteins. The invention also provides pharmaceutical compositions comprising said antibody proteins. The invention furthermore is concerned with the use in the manufacture of a medicament for the treatment of cancer.

Description

technical field [0001] The present invention belongs to the field of oncology. The present invention relates to an antibody with a specified sequence, which is specific to the epitope encoded by exon v6 of the CD44 gene variant, and to derivatives of the antibody. The invention also contemplates nucleic acid molecules encoding the antibody proteins. The invention further relates to methods of preparing the antibody protein. The present invention also proposes a pharmaceutical composition containing the antibody protein. The present invention is further related to the use of the medicine as a medicine for the treatment of cancer. Background technique [0002] In recent years it has been shown that the expression of variants of the surface glycoprotein CD44 is necessary and sufficient to induce the autonomous metastatic behavior of so-called non-metastatic rat pancreatic cancer cell lines as well as of non-metastatic rat fibrosarcoma cell lines. (Gunthert et al., 1991). W...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12N15/09A61KA61K31/00A61K31/375A61K39/395A61K47/10A61K47/48A61K51/00A61K51/10A61PA61P35/00A61P35/04C07KC07K16/18C07K16/28C07K16/46C07K19/00C12NC12N1/15C12N1/19C12N1/21C12N5/10C12N7/00C12N15/13C12N15/62C12N15/63C12P21/08
CPCC07K16/2884C07K2319/00A61K2039/505C12N2799/021A61P35/00A61P35/04
Inventor 冈瑟·阿道夫埃林伯格·奥斯特曼埃里克·帕特泽尔特马利斯·斯普罗尔卡尔-海因茨·海德约翰·J·米格利塔奥古斯蒂纽斯·A·M·S·范唐根
Owner BOEHRINGER INGELHEIM INT GMBH
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