WO1999054353A2 - Sequences d'acide nucleique humaines provenant du tissu normal de l'uterus - Google Patents

Sequences d'acide nucleique humaines provenant du tissu normal de l'uterus Download PDF

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Publication number
WO1999054353A2
WO1999054353A2 PCT/DE1999/001175 DE9901175W WO9954353A2 WO 1999054353 A2 WO1999054353 A2 WO 1999054353A2 DE 9901175 W DE9901175 W DE 9901175W WO 9954353 A2 WO9954353 A2 WO 9954353A2
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WO
WIPO (PCT)
Prior art keywords
undef
seq
nucleic acid
prostate
uterus
Prior art date
Application number
PCT/DE1999/001175
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German (de)
English (en)
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WO1999054353A3 (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 JP2000544691A priority Critical patent/JP2002512017A/ja
Priority to EP99924793A priority patent/EP1071777A2/fr
Publication of WO1999054353A2 publication Critical patent/WO1999054353A2/fr
Publication of WO1999054353A3 publication Critical patent/WO1999054353A3/fr

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    • 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
    • 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

Definitions

  • the invention relates to human nucleic acid sequences from uterine norm tissue which code for gene products or parts thereof, their functional genes, which code 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 an unmistakable pattern for a particular 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 1 to Seq. ID No.62 and Seq. ID 121 to Seq. ID 127 can be found, which play a role as candidate genes in the uterine tumor.
  • the nucleic acid sequences Seq are of particular interest. ID Nos. 1-20 and Seq. ID 121 to Seq. ID 127.
  • 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. 1-20 and Seq. ID 121 to Seq.lD
  • nucleic acid sequences mentioned under a) or c) an allelic variation of the nucleic acid sequences mentioned under a) or c) a 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 1-20 and Seq. ID 121 to Seq. ID 127 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. 62 and Seq. ID 121 to Seq. ID 127, which are expressed in increased amounts in the uterine norm 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 Nos 1-20 and Seq. Hybridize ID 121 to Seq. ID 127.
  • 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 used from ID 121 to Seq. ID 127 according to common procedural practice are constructed, wherein on the cassette at least one of the nucleic acid sequences according to the invention together with at least one control or regulatory sequence generally known to the person skilled in the art, such as, for. B. 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: la, 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 with suitable vectors into host cells in which the genetic information contained on the nucleic acid fragments, which is expressed, is located as a heterogeneous part and 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 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 Nos 63-117 and Seq. ID Nos. 131-151.
  • 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 Nos. 63-117 and Seq. ID Nos. 131-151.
  • 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. 1 to Seq. ID 62 and Seq. ID 121 to Seq.ID 127 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.
  • the nucleic acid sequences according to the invention can also be used in a phage display method.
  • the polypeptides according to the invention of the sequences Seq. ID Nos. 63-117 and Seq. ID Nos. 131-151 can also be used as a tool for finding active substances against the uterine 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. 1 to Seq. ID No. 62 and Seq. ID 121 to Seq. ID 127 for the expression of polypeptides which can be used as tools for finding active substances against the uterine tumor.
  • 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. 63-117 and Seq. ID Nos. 131-151 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 to Seq. ID No. 62 and Seq. ID 121 to Seq.ID 127, and their use together with suitable regulative elements, such as suitable promoters and / or enhancers.
  • Seq. ID No. 1 -62 and Seq. ID 121 to Seq. ID 127 are screened for genomic BAC, PAC and cosmid libraries 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. 1 to Seq. ID No. 62 and Seq. ID 121 to Seq. ID 127, 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.
  • 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
  • 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.
  • a partial DNA sequence S e.g. B. a single EST or a contig of ESTs, using a standard program for homoigies 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, Schaffer, A. A "Zhang, J., Zhang, Z., Miller, W. and Lipman, DJ (1997) Nucleic Acids
  • tissue-ordered (private or public) EST libraries certainly.
  • FASTA Pearson, WR and Lipman, DJ (1988) Proc. Natl. Acad. Sci. USA 85 2444-2448
  • 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 0.0120 0.85671.1673

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Biochemistry (AREA)
  • Genetics & Genomics (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Zoology (AREA)
  • Toxicology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Biophysics (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)

Abstract

L'invention concerne des séquences d'acide nucléique humaines (ARNm, ADNc, séquences génomiques) provenant du tissu normal de l'utérus, 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.
PCT/DE1999/001175 1998-04-17 1999-04-15 Sequences d'acide nucleique humaines provenant du tissu normal de l'uterus WO1999054353A2 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
JP2000544691A JP2002512017A (ja) 1998-04-17 1999-04-15 正常子宮組織からのヒト核酸配列
EP99924793A EP1071777A2 (fr) 1998-04-17 1999-04-15 Sequences d'acide nucleique humaines provenant du tissu normal de l'uterus

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE19817946A DE19817946A1 (de) 1998-04-17 1998-04-17 Menschliche Nukleinsäuresequenzen aus Uterus-Normalgewebe
DE19817946.4 1998-04-17

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WO1999054353A2 true WO1999054353A2 (fr) 1999-10-28
WO1999054353A3 WO1999054353A3 (fr) 2000-07-20

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Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001029084A2 (fr) * 1999-10-18 2001-04-26 Lexicon Genetics Incorporated Nouvelles proteines humaines et polynucleotides codant pour ces memes proteines
WO2001034796A1 (fr) * 1999-11-10 2001-05-17 Compugen Ltd. Homologues de type chordine
WO2001064885A1 (fr) * 2000-03-02 2001-09-07 Amgen, Inc. Molecules de type chordine 2 et utilisations de celles-ci
EP1241186A3 (fr) * 1998-04-22 2003-05-21 Genentech, Inc. Protéine gas-6 (growth arrest-specific gene 6) humaine et acides nucléiques le codant
WO2003050307A1 (fr) * 2001-12-05 2003-06-19 Genzyme Corporation Composes destines a la therapie et au diagnostic et procedes d'utilisation associes
WO2004007723A2 (fr) * 2002-07-17 2004-01-22 Cambridge University Technical Services Limited Genes
US6737062B2 (en) 2000-05-31 2004-05-18 Genzyme Corporation Immunogenic compositions
AU2002330288B2 (en) * 1998-03-10 2005-05-05 Genentech, Inc. Novel PRO213-1 PRO1330 and PRO1449 polypeptides and nucleic acids encoding same
JP2007289196A (ja) * 2000-10-02 2007-11-08 Bayer Corp 癌組織でディファレンシャルに発現される核酸配列
EP2050762A3 (fr) * 1998-03-10 2009-07-08 Genentech, Inc. Nouvelles polypeptides et acides nucléiques les codant
US7723488B2 (en) 1998-03-27 2010-05-25 Genentech, Inc. Monoclonal antibodies to secreted and transmembrane polypeptides
US8404811B2 (en) 2009-05-08 2013-03-26 Genentech, Inc. Humanized anti-EGFL7 antibodies and methods using same

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000053754A1 (fr) * 1999-03-08 2000-09-14 Genentech, Inc. Compositions et methodes pour le traitement de tumeurs
US6372473B1 (en) 1997-05-28 2002-04-16 Human Genome Sciences, Inc. Tissue plasminogen activator-like protease
EP1734998A2 (fr) 2004-04-14 2006-12-27 Genentech, Inc. Compositions et méthodes, comprenant un antagoniste de l'egfl7, destinées à la modulation du développement vasculaire

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WO1993024655A1 (fr) * 1992-05-27 1993-12-09 Amersham International Plc Analyse d'arn
WO1999055858A2 (fr) * 1998-04-28 1999-11-04 Metagen Gesellschaft Für Genomforschung Mbh Sequences nucleotidiques humaines obtenues a partir d'un tissu tumoral du pancreas

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WO1993024655A1 (fr) * 1992-05-27 1993-12-09 Amersham International Plc Analyse d'arn
WO1999055858A2 (fr) * 1998-04-28 1999-11-04 Metagen Gesellschaft Für Genomforschung Mbh Sequences nucleotidiques humaines obtenues a partir d'un tissu tumoral du pancreas

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CRESCENZI, E., ET AL.: "identification of differentially expressed mRNAs in normal and neoplastiic (adenocarcinoma) human endometrium" GYNECOLOGIC ONCOLOGY, Bd. 63, November 1996 (1996-11), Seiten 228-233, XP000874036 *
FANNON M R: "Gene expression in normal and disease states - identification of therapeutic targets" TRENDS IN BIOTECHNOLOGY,GB,ELSEVIER PUBLICATIONS, CAMBRIDGE, Bd. 14, Nr. 8, 1. August 1996 (1996-08-01), Seiten 294-298, XP004035748 ISSN: 0167-7799 *
HILLIER, L., ET AL.: "the WashU-Merck EST project - unpublished" EMBL SEQUENCE DATA LIBRARY, 7. September 1996 (1996-09-07), XP002129529 heidelberg, germany *
HILLIER, L., ET AL.: "the WashU-Merck EST project 1997" EMBL SEQUENCE DATA LIBRARY, 11. Juni 1997 (1997-06-11), XP002129531 heidelberg, germany *
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JANSA,P., ET AL.: "cloning and functional characterization of PTRF, a novel protein which induces dissociation of paused ternary transcription complexes" THE EMBO JOURNAL, Bd. 17, Nr. 10, 15. Mai 1998 (1998-05-15), Seiten 2855-2864, XP002129532 *
SCHMITT AO. ET AL.: "Exhaustive mining of EST libraries for genes differentially expressed in normal and tumour tissues." NUCLEIC ACID RESEARCH, Bd. 27, Nr. 21, November 1999 (1999-11), Seiten 4251-4260, XP002129533 *
SCHULER, G. D.: "Sequence mapping by electronic PCR" GENOME RESEARCH., Bd. 7, 1997, Seiten 541-550, XP002127628 ISSN: 1088-9051 in der Anmeldung erw{hnt *
WANG, Y. AND MIKSICEK, R.J.: "characterization of estrogen receptor cDNAs of human uterus: identification of a novel PvuII polymorphism" MOLECULAR AND CELLULAR ENDOCRINOLOGY, Bd. 101, 1994, Seiten 101-110, XP000874034 *

Cited By (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU2002330288B2 (en) * 1998-03-10 2005-05-05 Genentech, Inc. Novel PRO213-1 PRO1330 and PRO1449 polypeptides and nucleic acids encoding same
EP2050762A3 (fr) * 1998-03-10 2009-07-08 Genentech, Inc. Nouvelles polypeptides et acides nucléiques les codant
AU2002330288C1 (en) * 1998-03-10 2006-02-09 Genentech, Inc. Novel PRO213-1 PRO1330 and PRO1449 polypeptides and nucleic acids encoding same
US7723488B2 (en) 1998-03-27 2010-05-25 Genentech, Inc. Monoclonal antibodies to secreted and transmembrane polypeptides
EP1241186A3 (fr) * 1998-04-22 2003-05-21 Genentech, Inc. Protéine gas-6 (growth arrest-specific gene 6) humaine et acides nucléiques le codant
WO2001029084A3 (fr) * 1999-10-18 2001-11-01 Lexicon Genetics Inc Nouvelles proteines humaines et polynucleotides codant pour ces memes proteines
WO2001029084A2 (fr) * 1999-10-18 2001-04-26 Lexicon Genetics Incorporated Nouvelles proteines humaines et polynucleotides codant pour ces memes proteines
WO2001034796A1 (fr) * 1999-11-10 2001-05-17 Compugen Ltd. Homologues de type chordine
WO2001064885A1 (fr) * 2000-03-02 2001-09-07 Amgen, Inc. Molecules de type chordine 2 et utilisations de celles-ci
US6737062B2 (en) 2000-05-31 2004-05-18 Genzyme Corporation Immunogenic compositions
JP2007289196A (ja) * 2000-10-02 2007-11-08 Bayer Corp 癌組織でディファレンシャルに発現される核酸配列
WO2003050307A1 (fr) * 2001-12-05 2003-06-19 Genzyme Corporation Composes destines a la therapie et au diagnostic et procedes d'utilisation associes
WO2004007723A3 (fr) * 2002-07-17 2004-04-01 Univ Cambridge Tech Genes
US7488803B2 (en) 2002-07-17 2009-02-10 Cambridge Enterprise Limited Antibodies to the extracellular domain of human Fragilis polypeptide and methods of making said antibodies
WO2004007723A2 (fr) * 2002-07-17 2004-01-22 Cambridge University Technical Services Limited Genes
US8404811B2 (en) 2009-05-08 2013-03-26 Genentech, Inc. Humanized anti-EGFL7 antibodies and methods using same
US8574576B2 (en) 2009-05-08 2013-11-05 Genentech, Inc. Humanized anti-EGFL7 antibodies and methods using same

Also Published As

Publication number Publication date
EP1071777A2 (fr) 2001-01-31
DE19817946A1 (de) 1999-10-21
WO1999054353A3 (fr) 2000-07-20
JP2002512017A (ja) 2002-04-23

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