EP1068317A2 - Sequences d'acide nucleique humaines issues de tissus tumoraux prostatiques - Google Patents
Sequences d'acide nucleique humaines issues de tissus tumoraux prostatiquesInfo
- Publication number
- EP1068317A2 EP1068317A2 EP99917785A EP99917785A EP1068317A2 EP 1068317 A2 EP1068317 A2 EP 1068317A2 EP 99917785 A EP99917785 A EP 99917785A EP 99917785 A EP99917785 A EP 99917785A EP 1068317 A2 EP1068317 A2 EP 1068317A2
- Authority
- EP
- European Patent Office
- Prior art keywords
- undef
- seq
- nucleic acid
- prostate
- sequences
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
Definitions
- the invention relates to human nucleic acid sequences -mRNA, cDNA, genomic sequences- from tissue of prostate tumors that code for gene products or parts thereof and their use.
- the invention further relates to the polypeptides obtainable via the sequences and their use.
- a common type of cancer is prostate cancer, for which new therapies are necessary to combat it. Therapies used so far, which are based on the blocking of hormonal effects, are very often ineffective after a few years, since the tumor becomes hormone-independent. H. continues to grow without hormonal effects and forms metastases.
- ESTs are sequences of cDNAs, ie reverse-transcribed mRNAs, the molecules that reflect the expression of genes. The EST sequences are determined for normal and degenerate tissues. Various operators offer such databases commercially.
- the ESTs in the LifeSeq database used here are typically between 150 and 350 nucleotides long. They represent an unmistakable pattern for a particular gene, although this gene is usually much longer (> 2000 nucleotides).
- nucleic acid sequences Seq are of particular interest. ID No. 3, 4, 6; 10, 12, 15, 17-24, 27, 29, 31-34, 36, 39, 44-53; 142, 144-164.
- the invention thus relates to nucleic acid sequences encoding a gene product or a part thereof, comprising
- nucleic acid sequence selected from the group of nucleic acid sequences Seq. ID No. 3, 4, 6; 10, 12, 15, 17-24, 27, 29, 31 -34, 36, 39, 44-53; 142, 144-164,
- the invention further relates to a nucleic acid sequence according to one of the sequences Seq. ID No. 3, 4, 6; 10, 12, 15, 17-24, 27, 29, 31-34, 36, 39, 44-53; 142, 144-164 or a complementary or allelic variant thereof and the nucleic acid sequences thereof which have a 90% to 95% homology to a human nucleic acid sequence.
- the invention also relates to the nucleic acid sequences Seq. ID No. 3-53; 142, 144-164, which are increased expressed in prostate tumor tissue
- the invention further relates to nucleic acid sequences comprising a part of the above-mentioned nucleic acid sequences, in such a sufficient size that they can be combined with the sequences Seq. ID No. 3, 4, 6; 10, 12, 15, 17-24, 27, 29, 31-34, 36, 39, 44-53; 142, 144-164 hybridize.
- the nucleic acid sequences according to the invention generally have a length of at least 50 to 2000 bp, preferably a length of at least 150 to 1700 bp.
- expression cassettes can also be constructed in accordance with current process practice, with at least one of the nucleic acid sequences according to the invention together with at least one control or regulatory sequence known to the person skilled in the art, such as, for example, on the cassette.
- a suitable promoter is combined.
- the sequences according to the invention can be inserted in sense or antisense orientation.
- Expression cassettes or vectors are to be understood: 1. bacterial, such as. B., phagescript, pBs, ⁇ X174, pBluescript SK, pBs KS, pNH8a, pNH16a, pNH18a, pNH46a (Stratagene), pTrc99A, pKK223-3, pKK233-3, pDR540, pRIT5 (Pharmacia), like eukaryont, 2nd eukaryont.
- Suitable control or regulatory sequence means suitable promoters.
- Two preferred vectors are the pKK232-8 and the PCM7 vector.
- the following promoters are specifically meant: lad, lacZ, T3, T7, gpt, lambda PR, trc, CMV, HSV thymidine kinase, SV40, LTRs from retrovirus and mouse metallothionein-I.
- the DNA sequences on the expression cassette can encode a fusion protein which comprises a known protein and a biologically active polypeptide fragment.
- the expression cassettes are also the subject of the present invention.
- the nucleic acid fragments according to the invention can be used to produce full-length genes.
- the available genes are also the subject of the present invention.
- the invention also relates to the use of the nucleic acid sequences according to the invention and the gene fragments obtainable from the use.
- nucleic acid sequences according to the invention can be brought into host cells with suitable vectors, in which the heterologous part contains the genetic information contained on the nucleic acid fragments which is expressed.
- the host cells containing the nucleic acid fragments are also the subject of the present invention.
- Suitable host cells are e.g. B. prokaryotic cell systems such as E. coli or eukaryotic cell systems such as animal or human cells or yeasts.
- nucleic acid sequences according to the invention can be used in sense or antisense form.
- polypeptides or their fragments are produced by cultivating the host cells in accordance with common cultivation methods and then isolating and purifying the peptides or fragments, likewise by means of conventional methods.
- the invention further relates to nucleic acid sequences which encode at least a partial sequence of a biologically active polypeptide.
- the present invention relates to partial polypeptide sequences, so-called ORF (open reading frame) peptides, according to the sequence protocols Seq. ID No. 57-61, 64, 66-68, 70-71, 73-83, 85-87, 89-90, 92, 94, 95, 97, 101-141, 143 and 165-199.
- ORF open reading frame
- the invention further relates to the polypeptide sequences which have at least 80% homology, in particular 90% homology, to the polypeptide partial sequences according to the invention of Seq. ID No. 57-61, 64, 66-68, 70-71, 73-83, 85-87, 89-90, 92, 94, 95, 97, 101-141, 143 and 165-199.
- the invention also relates to antibodies which are directed against a polypeptide or a fragment which are derived from the nucleic acids of the sequences Seq. ID No. 3, 4, 6; 10, 12, 15, 17-24, 27, 29, 31-34, 36, 39, 44-53; 142, 144-164 can be encoded.
- Antibodies are to be understood in particular as monoclonal antibodies.
- the invention also relates to phage display proteins which are directed against a polypeptide or a fragment which are derived from the nucleic acids of the sequences Seq. ID No. 57-61, 64, 66-68, 70-71, 73-83, 85-87, 89-90, 92, 94, 95, 97, 101-141, 143 and 165-199.
- polypeptides according to the invention of the sequences Seq. ID No. 57-61, 64, 66-68, 70-71, 73-83, 85-87, 89-90, 92, 94, 95, 97, 101-141, 143 and 165-199 can also be found as a tool Active substances against prostate cancer are used, which is also the subject of the present invention.
- the present invention also relates to the use of the nucleic acid sequences according to the sequences Seq. ID No. 3, 4, 6; 10, 12, 15, 17-24, 27, 29, 31-34, 36, 39, 44-53; 142, 144-164 for the expression of polypeptides that can be used as tools for finding active substances against prostate cancer.
- the invention also relates to the use of the polypeptide partial sequences Seq found. ID No. 57-61, 64, 66-68, 70-71, 73-83, 85-87, 89-90, 92, 94, 95, 97, 101-141, 143 and 165-199 as drugs in gene therapy for treatment prostate cancer, or for the manufacture of a medicament for the treatment of prostate cancer.
- the invention also relates to medicaments which have at least one polypeptide partial sequence Seq. ID No. 57-61, 64, 66-68, 70-71, 73-83, 85-87, 89-90, 92, 94, 95, 97, 101-141, 143 and 165-199 included.
- the nucleic acid sequences according to the invention found can also be genomic or mRNA sequences.
- the invention also relates to genomic genes, their promoters, enhancers, silencers, exon structure, intron structure and their splice variants, obtainable from the cDNAs of the sequences Seq. ID No. 3, 4, 6; 10, 12, 15, 17-24, 27, 29, 31-34, 36, 39, 44-53; 142, 144-164, and their use together with suitable regulative elements, such as suitable promoters and / or enhancers.
- nucleic acids according to the invention are used to screen genomic BAC, PAC and cosmid libraries and use complementary ones
- BAC, PAC and cosmid clones specifically isolated human clones.
- the BAC, PAC and cosmid clones isolated in this way are hybridized with the aid of fluorescence in situ hybridization to metaphase chromosomes and corresponding chromosome sections on which the corresponding genomic genes lie are identified.
- BAC, PAC and cosmid clones are sequenced in order to elucidate the corresponding genomic genes in their complete structure (promoters, enhancers, silencers, exons and introns).
- BAC, PAC and cosmid clones can be used as independent molecules for gene transfer (see FIG. 5).
- the invention also relates to BAC, PAC and cosmid clones containing functional genes and their chromosomal localization, according to the sequences Seq. ID No. 3, 4, 6; 10, 12, 15, 17-24, 27, 29, 31-34, 36, 39, 44-53; 142, 144-164, for use as a gene transfer vehicle.
- nucleic acids nucleic acids are to be understood in the full invention: mRNA, partial cDNA, full length cDNA and genomic genes (chromosomes).
- ORF Open Reading Frame, a defined sequence of amino acids that can be derived from the cDNA sequence.
- Contig A lot of DNA sequences that are due to very large
- Module domain of a protein with a defined sequence that represents a structural unit and occurs in different proteins
- N either nucleotide A, T, G or C
- X optionally one of the 20 naturally occurring amino acids
- Fig. 1 shows the systematic gene search in the Incyte LifeSeq
- 4a shows the determination of the tissue-specific expression via electronic Northern.
- Figure 5 shows the isolation of BAC and PAC genomic clones.
- the following examples explain the preparation of the nucleic acid sequences according to the invention without restricting the invention to these examples and nucleic acid sequences.
- the singletons of the database which consisted of only one sequence, were reassembled with the sequences not included in the GAP4 database at 2% mismatch. Again, the consensus sequences were determined for the contigs. All other ESTs were reassembled at 4% mismatch. The consensus sequences were extracted again and finally assembled with the previous consensus sequences as well as the singletons and the sequences not included in the database at 4% mismatch. The consensus sequences were formed and used with the singletons and failures as the basis for the tissue comparisons. This procedure ensured that, under the parameters used, all sequences represented mutually independent gene regions.
- 2b1-2b4 illustrates the extension of the prostate tumor ESTs.
- Ratio of the frequency of occurrence in the respective tissues evaluated Ratio of the frequency of occurrence in the respective tissues evaluated.
- a partial DNA sequence S e.g. B. a single EST or a contig of ESTs are using a standard program for homology search, z. B. BLAST (Altschul, SF, Gish W., Miller, W., Myers, EW and Lipman, DJ (1990) J. Mol. Bio /., 215, 403-410), BLAST2 (Altschul, SF, Madden, T. L, Shuffer, AA, Zhang, J., Zhang, Z., Miller, W. and Lipman, DJ (1997) Nucleic Acids Research 25 3389-3402) or FASTA (Pearson, WR and Lipman, DJ (1988) Proc. Natl. Acad. Sci. USA 85 2444-2448), which determines homologous sequences in various EST libraries ordered by tissue (private or public).
- the (relative or absolute) tissue-specific occurrence frequencies of this partial sequence S determined in this way are referred to as electronic Northern blot.
- Seq. ID No. 40 found that occurs 8 times more strongly in prostate tumor tissue than in corresponding normal tissue.
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Toxicology (AREA)
- Molecular Biology (AREA)
- Urology & Nephrology (AREA)
- Engineering & Computer Science (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP02090141A EP1234879B1 (fr) | 1998-03-10 | 1999-03-09 | Séquence d'acide nucléique humaine issue de tissus tumoraux prostatiques |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19811193 | 1998-03-10 | ||
| DE19811193A DE19811193A1 (de) | 1998-03-10 | 1998-03-10 | Menschliche Nukleinsäuresequenzen aus Prostatatumorgewebe |
| PCT/DE1999/000721 WO1999046374A2 (fr) | 1998-03-10 | 1999-03-09 | Sequences d'acide nucleique humaines issues de tissus tumoraux prostatiques |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP02090141A Division EP1234879B1 (fr) | 1998-03-10 | 1999-03-09 | Séquence d'acide nucléique humaine issue de tissus tumoraux prostatiques |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| EP1068317A2 true EP1068317A2 (fr) | 2001-01-17 |
Family
ID=7860958
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP02090141A Expired - Lifetime EP1234879B1 (fr) | 1998-03-10 | 1999-03-09 | Séquence d'acide nucléique humaine issue de tissus tumoraux prostatiques |
| EP99917785A Withdrawn EP1068317A2 (fr) | 1998-03-10 | 1999-03-09 | Sequences d'acide nucleique humaines issues de tissus tumoraux prostatiques |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP02090141A Expired - Lifetime EP1234879B1 (fr) | 1998-03-10 | 1999-03-09 | Séquence d'acide nucléique humaine issue de tissus tumoraux prostatiques |
Country Status (5)
| Country | Link |
|---|---|
| EP (2) | EP1234879B1 (fr) |
| JP (1) | JP2002505877A (fr) |
| AT (1) | ATE399862T1 (fr) |
| DE (2) | DE19811193A1 (fr) |
| WO (1) | WO1999046374A2 (fr) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19813839A1 (de) * | 1998-03-20 | 1999-09-23 | Metagen Gesellschaft Fuer Genomforschung Mbh | Menschliche Nukleinsäuresequenzen aus Brusttumorgewebe |
| CA2369384A1 (fr) * | 1999-04-12 | 2000-10-19 | Agensys, Inc. | Nouveau gene specifique de la prostate exprime dans le cancer de la prostate |
| US6638734B1 (en) | 1999-06-11 | 2003-10-28 | The Burnham Institute | Nucleic acid encoding proteins involved in protein degradation, products and methods related thereto |
| AU5730300A (en) * | 1999-06-11 | 2001-01-02 | Burnham Institute, The | Nucleic acid encoding proteins involved in protein degradation, products and methods related thereto |
| US7504253B2 (en) | 1999-06-11 | 2009-03-17 | The Burnham Institute For Medical Research | Nucleic acid encoding proteins involved in protein degradation, products and methods related thereof |
| US7087386B2 (en) | 1999-06-11 | 2006-08-08 | The Burnham Institute | Nucleic acid encoding proteins involved in protein degradation, products and methods related thereto |
| WO2001023567A1 (fr) * | 1999-09-28 | 2001-04-05 | Zymogenetics, Inc. | Proteine-60 membranaire |
| EP1099757B1 (fr) | 1999-11-11 | 2010-02-24 | F. Hoffmann-La Roche Ag | Procédé pour détecter CTp11 et pour déterminer le potentiel métastatique d'un échantillon tumoral |
| AU749907B2 (en) | 1999-11-11 | 2002-07-04 | F. Hoffmann-La Roche Ag | Process for the determination of CTp11 and for determining whether a tumor sample has metastatic potential |
| US20020048777A1 (en) | 1999-12-06 | 2002-04-25 | Shujath Ali | Method of diagnosing monitoring, staging, imaging and treating prostate cancer |
| CA2409164A1 (fr) * | 2000-05-18 | 2001-11-22 | Hyseq, Inc. | Nouveaux acides nucleiques et polypeptides |
| DE10215321A1 (de) * | 2002-04-02 | 2003-10-23 | Metagen Pharmaceuticals Gmbh | Trp-p8 Splice Varianten und regulatorische RNA |
| JP2006115835A (ja) * | 2004-09-22 | 2006-05-11 | Univ Of Tokushima | 新規なパーキン結合タンパク質とその用途 |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2262403C (fr) * | 1995-07-31 | 2011-09-20 | Urocor, Inc. | Biomarqueurs et cibles de diagnostic, de pronostic et de traitement du cancer de la prostate |
| US5861248A (en) * | 1996-03-29 | 1999-01-19 | Urocor, Inc. | Biomarkers for detection of prostate cancer |
| US5843665A (en) * | 1996-10-31 | 1998-12-01 | Incyte Pharmaceuticals, Inc. | Human pyrophosphatase |
| CA2284550A1 (fr) * | 1997-03-21 | 1998-10-01 | Human Genome Sciences, Inc. | 87 proteines humaines secretees |
| US6194152B1 (en) * | 1997-08-20 | 2001-02-27 | Dendreon Corporation | Prostate tumor polynucleotide compositions and methods of detection thereof |
| DE19817557A1 (de) * | 1998-04-09 | 1999-10-21 | Metagen Gesellschaft Fuer Genomforschung Mbh | Menschliche Nukleinsäuresequenzen aus Ovartumorgewebe |
-
1998
- 1998-03-10 DE DE19811193A patent/DE19811193A1/de not_active Withdrawn
-
1999
- 1999-03-09 EP EP02090141A patent/EP1234879B1/fr not_active Expired - Lifetime
- 1999-03-09 EP EP99917785A patent/EP1068317A2/fr not_active Withdrawn
- 1999-03-09 DE DE59914802T patent/DE59914802D1/de not_active Expired - Lifetime
- 1999-03-09 JP JP2000535741A patent/JP2002505877A/ja active Pending
- 1999-03-09 AT AT02090141T patent/ATE399862T1/de not_active IP Right Cessation
- 1999-03-09 WO PCT/DE1999/000721 patent/WO1999046374A2/fr not_active Application Discontinuation
Non-Patent Citations (1)
| Title |
|---|
| See references of WO9946374A2 * |
Also Published As
| Publication number | Publication date |
|---|---|
| EP1234879B1 (fr) | 2008-07-02 |
| JP2002505877A (ja) | 2002-02-26 |
| DE19811193A1 (de) | 1999-09-16 |
| DE59914802D1 (de) | 2008-08-14 |
| WO1999046374A2 (fr) | 1999-09-16 |
| ATE399862T1 (de) | 2008-07-15 |
| EP1234879A2 (fr) | 2002-08-28 |
| EP1234879A3 (fr) | 2002-10-30 |
| WO1999046374A3 (fr) | 2000-07-06 |
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