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WO1999046375A2 - Sequences d'acide nucleique humaines issues de tissus tumoraux prostatiques - Google Patents

Sequences d'acide nucleique humaines issues de tissus tumoraux prostatiques Download PDF

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Publication number
WO1999046375A2
WO1999046375A2 PCT/DE1999/000722 DE9900722W WO9946375A2 WO 1999046375 A2 WO1999046375 A2 WO 1999046375A2 DE 9900722 W DE9900722 W DE 9900722W WO 9946375 A2 WO9946375 A2 WO 9946375A2
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WO
WIPO (PCT)
Prior art keywords
undef
prostate
seq
nucleic acid
lungs
Prior art date
Application number
PCT/DE1999/000722
Other languages
German (de)
English (en)
Other versions
WO1999046375A3 (fr
Inventor
Thomas Specht
Bernd Hinzmann
Armin Schmitt
Christian Pilarsky
Edgar Dahl
André ROSENTHAL
Original Assignee
Metagen Gesellschaft Für Genomforschung Mbh
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Metagen Gesellschaft Für Genomforschung Mbh filed Critical Metagen Gesellschaft Für Genomforschung Mbh
Priority to JP2000535742A priority Critical patent/JP2002505878A/ja
Priority to EP99920546A priority patent/EP1068318A2/fr
Publication of WO1999046375A2 publication Critical patent/WO1999046375A2/fr
Publication of WO1999046375A3 publication Critical patent/WO1999046375A3/fr

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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
    • A61P13/08—Drugs for disorders of the urinary system of the prostate
    • 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 normal prostate tissue, which 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 form of cancer is prostate cancer, and new ones are used to combat it
  • Therapies are necessary. 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 For the search for candidate genes, i.e. A database consisting of so-called ESTs is used for genes that are expressed more strongly in normal tissue compared to the tumor tissue.
  • ESTs are sequences of cDNAs, i.e. reverse transcribed mRNAs, the molecules that reflect the expression of genes.
  • the EST sequences are determined for normal and degenerate tissues. Such databases are partly used by various operators. offered 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). By comparing the expression patterns of normal and tumor tissue, ESTs can be identified that are important for tumor development and proliferation (see FIG. 1).
  • nucleic acid sequences Seq. ID No 2-4, 6-10, 12-14, 16-19, 21, 23, 24, 26-33, 35-37, 39, 41-44, 46, 47, 49, 51 -55, 58- 64 and Seq. ID No 217-247 can be found, which play a role as candidate genes in prostate cancer.
  • nucleic acid sequences Seq are of particular interest. ID. No. 3, 4, 6-8, 12, 16-19, 21, 23, 24, 26-33, 35, 37, 41 -44, 46, 47, 49, 51, 53, 54, 58-64 and 217- 247.
  • 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, 6-8, 12, 16-35, 37, 41 -44, 46, 47, 49, 51, 53, 54, 58-64 and 217-247,
  • the invention further relates to a nucleic acid sequence according to one of the
  • the invention also relates to the nucleic acid sequences Seq. ID No. 2-4, 6-10, 12-14, 16-19, 21, 23, 24, 26-33, 35-37, 39, 41-44, 46, 47, 49, 51-55, 58-64 and 217-247, which are increased expressed in normal prostate 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, 6-8, 12, 16-19, 21, 23, 24, 26-33, 35, 37, 41-44, 46, 47, 49, 51, 53, 54, 58-64 and 217- Hybridize 247.
  • the nucleic acid sequences according to the invention generally have a length of at least 50 to 2500 bp, preferably a length of at least 150 to 2000 bp, in particular a length of 400 to 1900 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, ⁇ f> X174, pBluescript SK, pBs KS, pNH8a, pNH16a, pNH18a, pNH46a (Stratagene), pTrc99A, pKK223-3, pKK233-3, pDR540, pRIT5 (Pharmacontic), 2. eukaryontician such as B. pWLneo, pSV2cat, pOG44, pXT1, pSG (Stratagene), pSVK3, pBPV, pMSG, pSVL (Pharmacia).
  • bacterial such as. B., phagescript, pBs, ⁇ f> X174, pBluescript SK, pBs KS, pNH8a, pNH16a, pNH18a, pNH46a (Strat
  • 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. 66-71, 73- 75, 82, 83, 90-93, 97-105, 109, 111-114, 116-124, 128-137, 139-149, 152, 154-165, 168-173, 183- 195, 214-216 and up to Seq. ID No. 248-295.
  • 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. 66-71, 73-75, 82, 83, 90-93, 97-105, 109, 111-114, 116-124, 128-137, 139-149, 152, 154-165, 168-173, 183- 195, 214-216 and up to Seq. ID No. 248-295.
  • 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. 66-71, 73-75, 82, 83, 90-93, 97-105, 109, 111-114, 116-124, 128-137, 139-149, 152, 154-165, 168-173, 183- 195, 214-216 and up to Seq. ID No. 248-295 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. 66-71, 73-75, 82, 83, 90-93, 97-105, 109, 111-114, 116-124, 128-137, 139-149, 152, 154-165, 168-173, 183- 195, 214-216 and up to Seq. ID No. 248-295 can be encoded.
  • polypeptides according to the invention of the sequences Seq. ID No. 66-71, 73-75, 82, 83, 90-93, 97-105, 109, 111-114, 116-124, 128-137, 139-149, 152, 154-165, 168-173, 183- 195, 214-216 and up to Seq. ID No. 248-295 can also be used as a tool for finding drugs against prostate cancer, 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. 66-71, 73-75, 82, 83, 90-93, 97-105, 109, 111-114, 116-124, 128-137, 139-149, 152, 154-165, 168-173, 183- 195, 214-216 and up to Seq. ID No. 248-295 for the expression of poiypeptides 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.
  • the invention also relates to medicaments which have at least one polypeptide partial sequence Seq. ID No. 66-71, 73-75, 82, 83, 90-93, 97-105, 109, 111-114, 116-124, 128-137, 139- 149, 152, 154-165, 168-173, 183- 195, 214-216 and up to Seq. ID No. 248-295 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, 6-8, 12, 16-19, 21, 23, 24, 26-33, 35, 37, 41-44, 46, 47, 49, 51, 53, 54, 58-64 and 217- 247, and their use together with suitable regulatory elements, such as suitable promoters and / or enhancers.
  • genomic BAC, PAC and cosmid libraries are screened and specifically human clones are isolated via complementary base pairing (hybridization).
  • 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 are identified on which the corresponding genomic genes lie.
  • 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, 6-8, 12, 16-19, 21, 23, 24, 26-33, 35, 37, 41-44, 46, 47, 49, 51, 53, 54, 58-64 and 217- 247, for use as a vehicle for gene transfer.
  • Nucleic acids nucleic acids are to be understood in the present 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
  • S ⁇ ngleton A contig that contains only one sequence.
  • 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.
  • 4b shows the electronic Northern
  • Figure 5 shows the isolation of BAC and PAC genomic clones.
  • 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.
  • Figures 2b1-2b4 illustrate the extension of normal prostate tissue ESTs.
  • 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. Biol., 215, 403-410), BLAST2 (Altschul, SF, Madden, T L, Schffer, AA, Zhang, J., Zhang, Z., Miller, W. and Lipman, DJ (1997) Nucleic Acids Research 25 3389-
  • tissue libraries private or public EST libraries.
  • FASTA Pearson, WR and Lipman, DJ (1988) Proc. Natl. Acad. Sci. USA 85 2444-2448.
  • tissue libraries private or public EST libraries.
  • the (relative or absolute) tissue-specific occurrence frequencies of this partial sequence S determined in this way are referred to as electronic Northern blot.
  • Musculoskeletal system 0.0103 0.0060 1.71300.5838
  • Musculoskeletal system 0.0103 0.0120 0.85651.1675

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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)
  • Bioinformatics & Cheminformatics (AREA)
  • Biophysics (AREA)
  • Urology & Nephrology (AREA)
  • Toxicology (AREA)
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  • Gastroenterology & Hepatology (AREA)
  • Biochemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Peptides Or Proteins (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)

Abstract

L'invention concerne des séquences d'acide nucléique humaines, ARNm, ADNc, séquences génomiques, issues de tissus prostatiques normaux, qui codent les produits géniques ou des parties de produits géniques, ainsi que l'utilisation desdites séquences. L'invention concerne en outre les polypeptides pouvant être obtenus par l'intermédiaire desdites séquences et leur utilisation.
PCT/DE1999/000722 1998-03-10 1999-03-09 Sequences d'acide nucleique humaines issues de tissus tumoraux prostatiques WO1999046375A2 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
JP2000535742A JP2002505878A (ja) 1998-03-10 1999-03-09 前立腺組織由来のヒト核酸配列
EP99920546A EP1068318A2 (fr) 1998-03-10 1999-03-09 Sequences d'acide nucleique humaines issues de tissus tumoraux prostatiques

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE19811194A DE19811194A1 (de) 1998-03-10 1998-03-10 Menschliche Nukleinsäuresequenzen aus Prostatagewebe
DE19811194.0 1998-03-10

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WO1999046375A2 true WO1999046375A2 (fr) 1999-09-16
WO1999046375A3 WO1999046375A3 (fr) 2000-07-06

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DE (1) DE19811194A1 (fr)
WO (1) WO1999046375A2 (fr)

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000073454A1 (fr) * 1999-06-02 2000-12-07 Genentech, Inc. Polypeptides transmembranaires secretes et acides nucleiques codants pour ceux-ci
WO2002036741A3 (fr) * 2000-10-30 2003-01-23 Bristol Myers Squibb Co Polynucleotide codant pour une proteine derivee d'un lymphocyte t humain active liee a une enzyme se conjuguant a l'ubiquitine
WO2004090098A3 (fr) * 2003-04-01 2006-02-16 Univ California Regulation de la transcription d'acide nucleique impliquant la phosphatase
US7119177B2 (en) 1997-06-16 2006-10-10 Genentech, Inc. Secreted and transmembrane polypeptides and nucleic acids encoding the same
US7264801B2 (en) 1998-08-11 2007-09-04 Genentech, Inc. EG-VEGF nucleic acids and polypeptides and method of use
US7446168B2 (en) 1998-08-11 2008-11-04 Genentech, Inc. EG-VEGF nucleic acids and polypeptides and methods of use

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000052175A1 (fr) * 1999-03-04 2000-09-08 Merck Patent Gmbh Histidine proteine phosphatase
AU2001247460A1 (en) * 2000-03-15 2001-09-24 Millennium Pharmaceuticals, Inc. 18615 and 48003, human ion channels and uses therefor

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0951541B1 (fr) * 1995-07-31 2005-11-30 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
WO1999006548A2 (fr) * 1997-08-01 1999-02-11 Genset Est 5' pour proteines secretees sans specificite tissulaire

Cited By (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7119177B2 (en) 1997-06-16 2006-10-10 Genentech, Inc. Secreted and transmembrane polypeptides and nucleic acids encoding the same
US7189814B2 (en) 1997-06-16 2007-03-13 Genentech, Inc. Secreted and transmembrane polypeptides and nucleic acids encoding the same
US7727536B2 (en) 1998-08-11 2010-06-01 Genentech, Inc. EG-VEGF nucleic acids and polypeptides and methods of use
US7264801B2 (en) 1998-08-11 2007-09-04 Genentech, Inc. EG-VEGF nucleic acids and polypeptides and method of use
US7446168B2 (en) 1998-08-11 2008-11-04 Genentech, Inc. EG-VEGF nucleic acids and polypeptides and methods of use
US7736645B2 (en) 1998-08-11 2010-06-15 Genentech, Inc. EG-VEGF nucleic acids and polypeptides and methods of use
US7960531B2 (en) 1998-08-11 2011-06-14 Genetech, Inc. EG-VEGF nucleic acids and polypeptides and methods of use
US8557238B2 (en) 1998-08-11 2013-10-15 Genentech, Inc. EG-VEGF nucleic acids and polypeptides and methods of use
WO2000073454A1 (fr) * 1999-06-02 2000-12-07 Genentech, Inc. Polypeptides transmembranaires secretes et acides nucleiques codants pour ceux-ci
EP1337544A4 (fr) * 2000-10-30 2004-12-08 Bristol Myers Squibb Co Polynucleotide codant pour une proteine derivee d'un lymphocyte t humain active liee a une enzyme se conjuguant a l'ubiquitine
EP1337544A2 (fr) * 2000-10-30 2003-08-27 Bristol-Myers Squibb Company Polynucleotide codant pour une proteine derivee d'un lymphocyte t humain active liee a une enzyme se conjuguant a l'ubiquitine
WO2002036741A3 (fr) * 2000-10-30 2003-01-23 Bristol Myers Squibb Co Polynucleotide codant pour une proteine derivee d'un lymphocyte t humain active liee a une enzyme se conjuguant a l'ubiquitine
WO2004090098A3 (fr) * 2003-04-01 2006-02-16 Univ California Regulation de la transcription d'acide nucleique impliquant la phosphatase

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JP2002505878A (ja) 2002-02-26
EP1068318A2 (fr) 2001-01-17
WO1999046375A3 (fr) 2000-07-06
DE19811194A1 (de) 1999-09-16

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