EP1080188A2 - Sequences d'acide nucleique provenant d'un fibrome uterin - Google Patents

Sequences d'acide nucleique provenant d'un fibrome uterin

Info

Publication number
EP1080188A2
EP1080188A2 EP99927686A EP99927686A EP1080188A2 EP 1080188 A2 EP1080188 A2 EP 1080188A2 EP 99927686 A EP99927686 A EP 99927686A EP 99927686 A EP99927686 A EP 99927686A EP 1080188 A2 EP1080188 A2 EP 1080188A2
Authority
EP
European Patent Office
Prior art keywords
seq
undef
nucleic acid
sequences
prostate
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Withdrawn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
EP99927686A
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 EP1080188A2 publication Critical patent/EP1080188A2/fr
Withdrawn legal-status Critical Current

Links

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 uterine fibroid 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.
  • One of the main causes of cancer death in women is the uterine fibroid, for which new therapies are necessary to combat it. Therapies used so far, such as Chemotherapy, hormone therapy or surgical removal of the tumor tissue often do not lead to complete healing.
  • the phenomenon of cancer is often associated with the over- or under-expression of certain genes in the degenerate cells, although it is still unclear whether these altered expression rates are the cause or the consequence of the malignant transformation.
  • ESTs Expressed Sequence Tags
  • cDNAs ie reverse-transcribed mRNAs
  • 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 a pattern unmistakable for a specific gene, although this gene is usually much longer (> 2000 nucleotides).
  • the nucleic acid sequences Seq are of particular interest. ID Nos. 14-18, 30, 31, 52.
  • 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 Nos. 14-18, 30, 31, 52.
  • nucleic acid sequence which is complementary to the nucleic acid sequences mentioned under a) or b).
  • the invention further relates to a nucleic acid sequence according to one of the sequences Seq ID Nos 14-18, 30, 31 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. 1 to Seq. ID No. 31 and and Seq. ID 52, which are expressed increased in the uterine fibroid.
  • 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. Hybridize ID Nos 14-18, 30, 31, 52.
  • 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.
  • 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 eg 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, 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.
  • 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 protocols ORF ID Nos 32-51 and ORF ID Nos 53-55.
  • the invention further relates to the polypeptide sequences which have at least 80% homology, in particular 90% homology, to the polypeptide partial sequences of the ORF according to the invention. ID Nos.
  • the invention also relates to antibodies which are directed against a polypeptide or fragment thereof which are of the nucleic acids of the sequences Seq. ID No. 1-31 and Seq.lD No. 52 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 Nos. 32-51 and Seq. ID Nos 53-55 can also be used as a tool for finding active substances against the uterine fibroid, 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. 1 to Seq. ID No. 31 and Seq. ID 52 for the expression of polypeptides that can be used as tools for finding active substances against the uterine fibroid.
  • the invention also relates to the use of the polypeptide partial sequences Seq found. ID No. 32 to Seq. ID No. 51 and Seq. ID Nos 53-55 as a drug in gene therapy for the treatment of the uterine fibroid, or for the manufacture of a drug for the treatment of the uterine fibroid.
  • the invention also relates to pharmaceutical compositions which contain at least one polypeptide partial sequence Seq. ID No. 32 to 51 and Seq. ID Nos 53-55 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. 1-31, 52, and their use together with suitable regulatory elements, such as suitable promoters and / or enhancers.
  • 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 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. 1-31, 52 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)
  • Module domain of a protein with a defined sequence, which represents a structural unit and occurs in different proteins
  • Fig. 1 shows the systematic gene search in the Incyte LifeSeq database.
  • Fig. 2a shows the principle of EST assembly.
  • Fig. 2b1-2b4 shows the entire principle of EST assembly.
  • Fig. 3 shows in silico subtraction of gene expression in different tissues
  • 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 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.
  • Musculoskeletal system 0.0737 0.0780 0.94451.0587
  • Musculoskeletal system 0.0308 0.0360 0.85671.1673
  • Gastrointestinal 0, .0122
  • Musculoskeletal system 0.0206 0.1140 0.18035.5448
  • Musculoskeletal system 0.0086 0. .0060 1.42780.7004
  • Musculoskeletal system 0.0771 0.0540 1.42780.7004
  • Musculoskeletal system 0.0069 0.0540 0.12697.8795

Landscapes

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

Abstract

L'invention concerne des séquences d'acide nucléique humaines (ARNm, ADNc, séquences génomiques) provenant d'une fibrome utérin, qui codent pour des produits géniques ou pour des parties desdits produits géniques, ainsi que leur utilisation. Elle concerne également les polypeptides codés par lesdites séquences et leur utilisation.
EP99927686A 1998-04-17 1999-04-15 Sequences d'acide nucleique provenant d'un fibrome uterin Withdrawn EP1080188A2 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DE19817947A DE19817947A1 (de) 1998-04-17 1998-04-17 Menschliche Nukleinsäuresequenzen aus Myometrium-Tumorgewebe
DE19817947 1998-04-17
PCT/DE1999/001178 WO1999054448A2 (fr) 1998-04-17 1999-04-15 Sequences d'acide nucleique provenant d'un fibrome uterin

Publications (1)

Publication Number Publication Date
EP1080188A2 true EP1080188A2 (fr) 2001-03-07

Family

ID=7865425

Family Applications (1)

Application Number Title Priority Date Filing Date
EP99927686A Withdrawn EP1080188A2 (fr) 1998-04-17 1999-04-15 Sequences d'acide nucleique provenant d'un fibrome uterin

Country Status (4)

Country Link
EP (1) EP1080188A2 (fr)
JP (1) JP2002512024A (fr)
DE (1) DE19817947A1 (fr)
WO (1) WO1999054448A2 (fr)

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU4004200A (en) * 1999-02-26 2000-09-14 Zymogenetics Inc. Mammalian alpha-helical protein, zsig83
AU1486801A (en) * 1999-11-15 2001-05-30 Curagen Corporation Novel growth factor polypeptides and nucleic acids encoding same
WO2002024867A2 (fr) * 2000-09-22 2002-03-28 University Of Aarhus Nouvelles compositions et nouvelles methodes pour le diagnostic et le traitement des lymphomes et des leucemies
US20060063230A1 (en) 2000-12-27 2006-03-23 Roman Naworth Sulfatases and methods of use thereof
WO2003006688A2 (fr) * 2001-07-13 2003-01-23 University Of Aarhus Methodes de diagnostic et de traitement des maladies associees a l'expression alteree de gnas
AU2002330713A1 (en) * 2001-09-24 2003-04-07 University Of Aarhus Methods for diagnosis and treatment of diseases associated with altered expression of neurogranin

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO9954448A3 *

Also Published As

Publication number Publication date
DE19817947A1 (de) 1999-10-28
WO1999054448A2 (fr) 1999-10-28
JP2002512024A (ja) 2002-04-23
WO1999054448A3 (fr) 2000-07-06

Similar Documents

Publication Publication Date Title
EP1291422A2 (fr) Sequences d'acide nucleique humaine provenant de tissu de tumeur ovarienne
DE19817948A1 (de) Menschliche Nukleinsäuresequenzen aus Endometrium-Tumor
EP1236799A2 (fr) Séquences d'acides nucléiques humaines issues du tissu de tumeur du sein
DE19820190A1 (de) Menschliche Nukleinsäuresequenzen aus Pankreas-Tumor
DE19816395A1 (de) Menschliche Nukleinsäuresequenzen aus Ovar-Normalgewebe
EP1234879B1 (fr) Séquence d'acide nucléique humaine issue de tissus tumoraux prostatiques
DE19818620A1 (de) Menschliche Nukleinsäuresequenzen aus Blase-Normal
EP1071777A2 (fr) Sequences d'acide nucleique humaines provenant du tissu normal de l'uterus
EP1073742A2 (fr) Sequences d'acide nucleique provenant de tissus tumoraux de la vessie
EP1080188A2 (fr) Sequences d'acide nucleique provenant d'un fibrome uterin
EP1206535A1 (fr) Antigene (r11) specifique de tumeur
DE19813835A1 (de) Menschliche Nukleinsäuresequenzen aus Brustnormalgewebe
DE69434090T2 (de) Epsilon-untereinheit des gaba a-rezeptors
DE19811194A1 (de) Menschliche Nukleinsäuresequenzen aus Prostatagewebe
EP1082420A2 (fr) Sequences d'acides nucleiques humains provenant de tissus sains du pancreas
US20030105315A1 (en) Human nucleic acid sequences from ovarian tumor tissue
DE60122684T2 (de) Akuter neuronal-induzierter liganden des calcium-bindenden protein-1
US20040002471A1 (en) Human nucleic acid sequences which are overexpressed in normal pancreas tissue
DE19958680A1 (de) cDNA-Sequenzen von zwei Interaktoren FANCIP4 und FANCIP5 der Fanconi-Anämie-Pr oteine der Komplementationsgruppen A und C
WO2000046244A1 (fr) SEQUENCE D'ADNc D'UNE PROTEINE D'INTERACTION FANCIP1 DE LA PROTEINE DE L'ANEMIE DE FANCONI DU GROUPE DE COMPLEMENTATION A

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 20001010

AK Designated contracting states

Kind code of ref document: A2

Designated state(s): AT BE CH CY DE DK ES FI FR GB GR IE IT LI NL PT SE

RAP1 Party data changed (applicant data changed or rights of an application transferred)

Owner name: METAGEN PHARMACEUTICALS GMBH

17Q First examination report despatched

Effective date: 20040121

RAP1 Party data changed (applicant data changed or rights of an application transferred)

Owner name: PILARSKY, CHRISTIAN, DR.

Owner name: SPECHT, THOMAS, DR.

Owner name: ROSENTHAL, ANDRE, PROF.

Owner name: HINZMANN, BERND, DR.

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN

18D Application deemed to be withdrawn

Effective date: 20040803