EP1056764A1 - Sekretierte proteine und für sie kodierende polynukleotide - Google Patents

Sekretierte proteine und für sie kodierende polynukleotide

Info

Publication number
EP1056764A1
EP1056764A1 EP99907121A EP99907121A EP1056764A1 EP 1056764 A1 EP1056764 A1 EP 1056764A1 EP 99907121 A EP99907121 A EP 99907121A EP 99907121 A EP99907121 A EP 99907121A EP 1056764 A1 EP1056764 A1 EP 1056764A1
Authority
EP
European Patent Office
Prior art keywords
seq
polynucleotide
protein
nucleotide
amino acid
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Withdrawn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
EP99907121A
Other languages
English (en)
French (fr)
Other versions
EP1056764A4 (de
Inventor
Kenneth Jacobs
John M. Mccoy
Edward R. Lavallie
Lisa A. Collins-Racie
David Merberg
Maurice Treacy
Michael J. Agostino
Robert J. Ii Steininger
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.)
Genetics Institute LLC
Original Assignee
Genetics Institute LLC
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 Genetics Institute LLC filed Critical Genetics Institute LLC
Publication of EP1056764A1 publication Critical patent/EP1056764A1/de
Publication of EP1056764A4 publication Critical patent/EP1056764A4/de
Withdrawn legal-status Critical Current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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • 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 present invention provides novel polynucleotides and proteins encoded by such polynucleotides, along with therapeutic, diagnostic and research utilities for these polynucleotides and proteins.
  • such polynucleotide comprises the nucleotide sequence of SEQ ID NO:7 from nucleotide 51 to nucleotide 1202; the nucleotide sequence of the full-length protein coding sequence of clone lp547_4 deposited under accession number ATCC 98663; or the nucleotide sequence of a mature protein coding sequence of clone lp547_4 deposited under accession number ATCC 98663.
  • the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone lp547_4 deposited under accession number ATCC 98663.
  • (k) a polynucleotide which encodes a species homologue of the protein of (h) or (i) above ; (1) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(i); and
  • a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone nq34_12 deposited under accession number ATCC 98663;
  • the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID NO:14 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID NO:14, or a protein comprising a fragment of the amino acid sequence of SEQ ID NO: 14 having biological activity, the fragment comprising the amino acid sequence from amino acid 28 to amino acid 37 of SEQ ID NO:14.
  • inventions provide the gene conesponding to the cDNA sequence of SEQ ID NO:17.
  • Further embodiments of the invention provide isolated polynucleotides produced according to a process selected from the group consisting of: (a) a process comprising the steps of:
  • polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(i) and that has a length that is at least 25% of the length of SEQ ID NO:19.
  • such polynucleotide comprises the nucleotide sequence of SEQ ID NO:19 from nucleotide 172 to nucleotide 1041; the nucleotide sequence of SEQ ID NO:19 from nucleotide 295 to nucleotide 1041; the nucleotide sequence of the full-length protein coding sequence of clone qoll5_13 deposited under accession number ATCC 98663; or the nucleotide sequence of a mature protein coding sequence of clone qoll5_13 deposited under accession number ATCC 98663.
  • the nucleotide sequence of SEQ ID NO:19 from nucleotide 172 to nucleotide 1041
  • the polynucleotide is operably linked to an expression control sequence.
  • the invention also provides a host cell, including bacterial, yeast, insect and mammalian cells, transformed with such polynucleotide compositions. Also provided by the present invention are organisms that have enhanced, reduced, or modified expression of the gene(s) corresponding to the polynucleotide sequences disclosed herein.
  • the EcoRI/Notl restriction fragment obtainable from the deposit containing clone co821_31 should be approximately 2400 bp.
  • ptl27_l A polynucleotide of the present invention has been identified as clone "ptl27_l".
  • ptl27_l was isolated from a human adult blood (lymphoblastic leukemia MOLT-4) cDNA library using methods which are selective for cDNAs encoding secreted proteins (see U.S.
  • the oligonucleotide should preferably be labeled with ⁇ - 32 P ATP (specific activity 6000 Ci/mmole) and T4 polynucleotide kinase using commonly employed techniques for labeling oligonucleotides. Other labeling techniques can also be used. Unincorporated label should preferably be removed by gel filtration chromatography or other established methods. The amount of radioactivity incorporated into the probe should be quantitated by measurement in a scintillation counter. Preferably, specific activity of the resulting probe should be approximately 4e+6 dpm/pmole.
  • the present invention also includes polynucleotides that hybridize under reduced stringency conditions, more preferably stringent conditions, and most preferably highly stringent conditions, to polynucleotides described herein.
  • stringency conditions are shown in the table below: highly stringent conditions are those that are at least as stringent as, for example, conditions A-F; stringent conditions are at least as stringent as, for example, conditions G-L; and reduced stringency conditions are at least as stringent as, for example, conditions M-R.
  • Modifications of interest in the protein sequences may include the alteration, substitution, replacement, insertion or deletion of a selected amino acid residue in the coding sequence.
  • one or more of the cysteine residues may be deleted or replaced with another amino acid to alter the conformation of the molecule.
  • Techniques for such alteration, substitution, replacement, insertion or deletion are well known to those skilled in the art (see, e.g., U.S. Patent No.4,518,584).
  • such alteration, substitution, replacement, insertion or deletion retains the desired activity of the protein.
  • the protein binds or potentially binds to another protein (such as, for example, in a receptor-ligand interaction)
  • the protein can be used to identify the other protein with which binding occurs or to identify inhibitors of the binding interaction. Proteins involved in these binding interactions can also be used to screen for peptide or small molecule inhibitors or agonists of the binding interaction.
  • a molecule which inhibits or blocks interaction of a B7 lymphocyte antigen with its natural hgand(s) on immune cells such as a soluble, monomeric form of a peptide having B7-2 activity alone or in conjunction with a monomenc form of a peptide havmg an activity of another B lymphocyte antigen (e g., B7- 1, B7-3) or blocking antibody)
  • a B7 lymphocyte antigen e g., B7- 1, B7-3 or blocking antibody
  • Blocking B lymphocyte antigen function prevents cytokine synthesis by immune cells, such as T cells, and thus acts as an immunosuppressant
  • the lack of costimulation may also be sufficient to anergize the T cells, thereby inducing tolerance in a subject Induction of long-term
  • B lymphocyte antigen-blocking reagents may avoid the necessity of repeated administration of these blocking reagents. To achieve sufficient immunosuppression or tolerance in a subject, it may also be necessary to block the function of a combination of B lymphocyte antigens.
  • the efficacy of particular blocking reagents in preventing organ transplant rejection or GNHD can be assessed using animal models that are predictive of efficacy in humans.
  • Upregulation of an antigen function (preferably a B lymphocyte antigen function), as a means of up regulating immune responses, may also be useful in therapy. Upregulation of immune responses may be in the form of enhancing an existing immune
  • the activity of a protem of the invention may, among other means, be measured by the following methods:
  • Proteins of the invention may also be useful to promote better or faster closure of non-healing wounds, including without limitation pressure ulcers, ulcers associated with vascular insufficiency, surgical and traumatic wounds, and the like.
  • the activity of a protein of the invention may, among other means, be measured by the following methods:
  • Proteins exhibiting such activities can be used to treat inflammatory conditions including chronic or acute conditions), including without limitation inflammation associated with infection (such as septic shock, sepsis or systemic inflammatory response syndrome (SIRS)), ischemia-reperfusion injury, endotoxin lethality, arthritis, complement-mediated hyperacute rejection, nephritis, cytokine or chemokine-induced lung injury, inflammatory bowel disease, Crohn's disease or resulting from over production of cytokines such as TNF or IL-1. Proteins of the invention may also be useful to treat anaphylaxis and hypersensitivity to an antigenic substance or material.
  • infection such as septic shock, sepsis or systemic inflammatory response syndrome (SIRS)
  • ischemia-reperfusion injury such as endotoxin lethality, arthritis, complement-mediated hyperacute rejection, nephritis, cytokine or chemokine-induced lung injury, inflammatory bowel disease, Crohn's disease or resulting
  • Fragments of proteins of the present invention with cadherin activity preferably a polypeptide comprising a decapeptide of the cadherin recognition site, and polynucleotides of the present invention encoding such protein fragments, can also be used to block cadherin function by binding to cadherins and preventing them from binding in ways that produce undesirable effects. Additionally, fragments of proteins of the present invention with cadherin activity, preferably truncated soluble cadherin fragments which have been found to be stable in the circulation of cancer patients, and polynucleotides encoding such protein fragments, can be used to disturb proper cell-cell adhesion.
  • the pharmaceutical composition of the invention may be in the form of a liposome in which protein of the present invention is combined, in addition to other pharmaceutically acceptable carriers, with amphipathic agents such as lipids which exist in aggregated form as micelles, insoluble monolayers, liquid crystals, or lamellar layers in aqueous solution.
  • Suitable lipids for liposomal formulation include, without limitation, monoglycerides, diglycerides, sulfatides, lysolecithin, phospholipids, saponin, bile acids, and the like. Preparation of such liposomal formulations is within the level of skill in the art, as disclosed, for example, in U.S. Patent No. 4,235,871; U.S. Patent No. 4,501,728; U.S. Patent No. 4,837,028; and U.S. Patent No. 4,737,323, all of which are incorporated herein by reference.
  • Protem of the invention may also be used to immunize animals to obtain polyclonal and monoclonal antibodies which specifically react with the protem
  • Such antibodies may be obtamed usmg either the entire protem or fragments thereof as an immunogen
  • the peptide immunogens additionally may contam a cysteme residue at the carboxyl terminus, and are conjugated to a hapten such as keyhole limpet hemocyanin (KLH) Methods for synthesizing such peptides are known in the art, for example, as m
  • Cells may also be cultured ex vivo in the presence of proteins of the present invention in order to proliferate or to produce a desired effect on or activity in such cells. Treated cells can then be introduced in vivo for therapeutic purposes.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Gastroenterology & Hepatology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Animal Behavior & Ethology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Public Health (AREA)
  • Engineering & Computer Science (AREA)
  • Toxicology (AREA)
  • Zoology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (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)
EP99907121A 1998-02-18 1999-02-18 Sekretierte proteine und für sie kodierende polynukleotide Withdrawn EP1056764A4 (de)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US251600 1981-04-06
US7503898P 1998-02-18 1998-02-18
US75038P 1998-02-18
US25160099A 1999-02-17 1999-02-17
PCT/US1999/003458 WO1999042470A1 (en) 1998-02-18 1999-02-18 Secreted proteins and polynucleotides encoding them

Publications (2)

Publication Number Publication Date
EP1056764A1 true EP1056764A1 (de) 2000-12-06
EP1056764A4 EP1056764A4 (de) 2001-08-29

Family

ID=26756362

Family Applications (1)

Application Number Title Priority Date Filing Date
EP99907121A Withdrawn EP1056764A4 (de) 1998-02-18 1999-02-18 Sekretierte proteine und für sie kodierende polynukleotide

Country Status (5)

Country Link
EP (1) EP1056764A4 (de)
JP (1) JP2002504488A (de)
AU (1) AU2685599A (de)
CA (1) CA2320799A1 (de)
WO (1) WO1999042470A1 (de)

Families Citing this family (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997012898A1 (en) 1995-10-06 1997-04-10 President And Fellows Of Harvard College Novel platelet activation protein
US20080213778A1 (en) 1998-12-30 2008-09-04 Millennium Pharmaceuticals, Inc. Novel genes encoding proteins having prognostic, diagnostic, preventive, therapeutic, and other uses
US7041474B2 (en) 1998-12-30 2006-05-09 Millennium Pharmaceuticals, Inc. Nucleic acid encoding human tango 509
US6558910B2 (en) 1999-09-10 2003-05-06 The Regents Of The University Of California SF, a novel family of taste receptors
EP1214343A2 (de) 1999-09-10 2002-06-19 The Regents Of The University Of California T2r geschmacksrezeptorfamilie
EP1218411A4 (de) * 1999-09-20 2004-09-01 Millennium Pharm Inc Sekretierte proteine und ihre verwendung
JP2003513662A (ja) * 1999-11-09 2003-04-15 ヒューマン ジノーム サイエンシーズ， インコーポレイテッド １５個のヒト分泌タンパク質
AU5125801A (en) 2000-04-07 2001-10-23 Senomyx Inc T2r taste receptors and genes encoding same
AU2001249898A1 (en) * 2000-04-10 2001-10-23 Human Genome Sciences, Inc. Tm4sf receptor polynucleotides, polypeptides, and antibodies
IL165669A0 (en) 2002-07-29 2006-01-15 Senomyx Inc Identification of a novel bitter taste receptor t2r76

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
No further relevant documents disclosed *
See also references of WO9942470A1 *

Also Published As

Publication number Publication date
WO1999042470A1 (en) 1999-08-26
CA2320799A1 (en) 1999-08-26
AU2685599A (en) 1999-09-06
EP1056764A4 (de) 2001-08-29
JP2002504488A (ja) 2002-02-12

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