EP1082420A2 - Sequences d'acides nucleiques humains provenant de tissus sains du pancreas - Google Patents

Sequences d'acides nucleiques humains provenant de tissus sains du pancreas

Info

Publication number
EP1082420A2
EP1082420A2 EP99945722A EP99945722A EP1082420A2 EP 1082420 A2 EP1082420 A2 EP 1082420A2 EP 99945722 A EP99945722 A EP 99945722A EP 99945722 A EP99945722 A EP 99945722A EP 1082420 A2 EP1082420 A2 EP 1082420A2
Authority
EP
European Patent Office
Prior art keywords
undef
nucleic acid
seq
sequences
acid sequence
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Withdrawn
Application number
EP99945722A
Other languages
German (de)
English (en)
Inventor
Thomas Specht
Bernd Hinzmann
Armin Schmitt
Christian Pilarsky
Edgar Dahl
André ROSENTHAL
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Hinzmann Bernd Dr
PILARSKY, CHRISTIAN, DR.
ROSENTHAL, ANDRE, PROF.
SPECHT, THOMAS, DR.
Original Assignee
Metagen Gesellschaft fur 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 fur Genomforschung Mbh filed Critical Metagen Gesellschaft fur Genomforschung Mbh
Publication of EP1082420A2 publication Critical patent/EP1082420A2/fr
Withdrawn legal-status Critical Current

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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
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides

Definitions

  • the invention relates to human nucleic acid sequences from normal pancreatic tissue which code for gene products or parts thereof, their functional genes, which code for at least one biologically active polypeptide and their use.
  • the invention further relates to the polypeptides obtainable via the sequences and their use.
  • ESTs Extracellular DNA sequences
  • cDNAs i.e. reverse transcribed mRNAs
  • 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 a pattern unmistakable for a specific gene, although this gene is usually much longer (> 2000 nucleotides).
  • ESTs can be identified that are important for tumor development and proliferation.
  • the EST sequences found can belong to different regions of an unknown gene due to different constructions of the cDNA libraries, in such a case there would be a completely wrong ratio of the occurrence of these ESTs in the respective tissue. This would only be noticed when the complete gene is known and the ESTs can thus be assigned to the same gene.
  • the nucleic acid sequences Seq. ID No 2-37, 67 can be found, which play a role as candidate genes in the pancreatic tumor.
  • the nucleic acid sequences Seq are of particular interest. ID No 14, 24, 25, 27-31, 35-37, 67.
  • the invention thus relates to nucleic acid sequences which encode a gene product or a part thereof, comprising a) a nucleic acid sequence selected from the group of the nucleic acid sequences Seq. ID No 14, 24, 25, 27-31, 35-37, 67.
  • the invention further relates to a nucleic acid sequence according to one of the sequences Seq. ID No 14, 24, 25, 27-31, 35-37, 67 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 2-37, 67, which are expressed increased in normal pancreatic 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 14, 24, 25, 27-31, 35-37, 67 hybridize.
  • the nucleic acid sequences according to the invention generally have a length of at least 50 to 4500 bp, preferably a length of at least 150 to 4000 bp, in particular a length of 450 to 3500 bp.
  • 67 can also be constructed in accordance with current process practice, wherein 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, B. a suitable promoter is combined.
  • the sequences according to the invention can be inserted in sense or antisense orientation. A large number of expression cassettes or vectors and promoters are known in the literature which can be used.
  • Expression cassettes or vectors are to be understood: 1. bacterial, such as. B., phagescript, pBs, ⁇ X174, pBluescript SK, pBs KS, pNH ⁇ a, pNH16a, pNH18a, pNH46a (Stratagene), pTrc99A, pKK223-3, pKK233-3, pDR540, pRlT5 (Pharmacia), such as 2. B. pWLneo, pSV2cat, pOG44, pXT1, pSG (Stratagene), pSVK3, pBPV, pMSG, pSVL (Pharmacia).
  • bacterial such as. B., phagescript, pBs, ⁇ X174, pBluescript SK, pBs KS, pNH ⁇ a, pNH16a, pNH18a, pNH46a (Stratagene), pTrc99A
  • 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 Pp, 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.
  • the 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.
  • the 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 protocoils Seq. ID No 39-63, 68-71.
  • 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 39-63, 68-71.
  • the invention also relates to antibodies which are directed against a polypeptide or fragment thereof, which of the nucleic acids of the sequences Seq. ID No 2-37, 67 can be encoded.
  • Antibodies are to be understood in particular as monoclonal antibodies.
  • the antibodies of the invention can include can be identified by a phage display method. These antibodies are also the subject of the invention.
  • the partial polypeptide sequences according to the invention can be used in a phage display method.
  • the polypeptides identified by this method which bind to the partial polypeptide sequences according to the invention are also the subject of the invention.
  • nucleic acid sequences according to the invention can also be used in a phage display method.
  • polypeptides according to the invention of the sequences Seq. ID No 39-63, 68-71 can also be used as a tool for finding active substances against the pancreatic tumor, 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 2-37, 67 for the expression of polypeptides that can be used as tools for finding active substances against the pancreatic tumor.
  • the invention also relates to the use of the polypeptide partial sequences Seq found. ID No 39-63, 68-71 as a medicament in gene therapy for the treatment against the pancreatic tumor, or for the manufacture of a medicament for the treatment against the pancreatic tumor.
  • the invention also relates to medicaments which have at least one polypeptide partial sequence Seq. ID No 39-63, 68-71 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 exon and intron structure and their splice variants, obtainable from the cDNAs of the sequences Seq. ID No 2-37, 67, and their use together with suitable regulative elements, such as suitable promoters and / or enhancers.
  • suitable regulative elements such as suitable promoters and / or enhancers.
  • 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 2-37, 67, for use as a vehicle for gene transfer.
  • 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 set of DNA sequences that can be combined into one sequence due to their very similarities (consensus)
  • Fig. 1 shows the systematic gene search in the Incyte LifeSeq database.
  • 4a shows the determination of the tissue-specific expression via electronic Northern.
  • Fig. 4b shows the electronic Northern
  • Fig. 5 shows the isolation of genomic BAC and PAC clones.
  • a partial DNA sequence S e.g. B. a single EST or a contig of ESTs are using a standard homology search program, e.g. 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, Schaffer, 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.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Zoology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Toxicology (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)

Abstract

L'invention concerne des séquences d'acides nucléiques humains - ARNm, ADNc, séquences génomiques - provenant de tissus sains du pancréas, qui codent pour des produits géniques ou des fragments de ces derniers. L'invention concerne également l'utilisation desdites séquences, ainsi que les polypeptides pouvant être obtenus par l'intermédiaire desdites séquences, et l'utilisation de ces polypeptides.
EP99945722A 1998-04-19 1999-04-08 Sequences d'acides nucleiques humains provenant de tissus sains du pancreas Withdrawn EP1082420A2 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DE19818598A DE19818598A1 (de) 1998-04-19 1998-04-19 Menschliche Nukleinsäuresequenzen aus Pankreasnormalgewebe
DE19818598 1998-04-19
PCT/DE1999/001096 WO1999054446A2 (fr) 1998-04-19 1999-04-08 Sequences d'acides nucleiques humains provenant de tissus sains du pancreas

Publications (1)

Publication Number Publication Date
EP1082420A2 true EP1082420A2 (fr) 2001-03-14

Family

ID=7865819

Family Applications (1)

Application Number Title Priority Date Filing Date
EP99945722A Withdrawn EP1082420A2 (fr) 1998-04-19 1999-04-08 Sequences d'acides nucleiques humains provenant de tissus sains du pancreas

Country Status (4)

Country Link
EP (1) EP1082420A2 (fr)
JP (1) JP2002512022A (fr)
DE (1) DE19818598A1 (fr)
WO (1) WO1999054446A2 (fr)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000020447A2 (fr) * 1998-10-06 2000-04-13 Curagen Corporation Nouvelles proteines secretees, et polynucleotides les codant
WO2000031243A1 (fr) * 1998-11-20 2000-06-02 Fuso Pharmaceutical Industries, Ltd. Nouvelle serine protease bssp5
CA2395872A1 (fr) * 2000-01-31 2001-08-02 Human Genome Sciences, Inc. Acides nucleiques, proteines et anticorps

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO9954446A3 *

Also Published As

Publication number Publication date
WO1999054446A2 (fr) 1999-10-28
JP2002512022A (ja) 2002-04-23
WO1999054446A3 (fr) 2000-06-02
DE19818598A1 (de) 1999-10-21

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