WO1999006427A1 - Molecules d'acide nucleique tango-78, tango-79 et tango-81 - Google Patents

Molecules d'acide nucleique tango-78, tango-79 et tango-81 Download PDF

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Publication number
WO1999006427A1
WO1999006427A1 PCT/US1998/016241 US9816241W WO9906427A1 WO 1999006427 A1 WO1999006427 A1 WO 1999006427A1 US 9816241 W US9816241 W US 9816241W WO 9906427 A1 WO9906427 A1 WO 9906427A1
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Prior art keywords
tango
seq
polypeptide
atcc
amino acid
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PCT/US1998/016241
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English (en)
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Sean A. Mccarthy
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Millennium Biotherapeutics, Inc.
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Priority to CA002299276A priority Critical patent/CA2299276A1/fr
Priority to JP2000505183A priority patent/JP2001512003A/ja
Priority to EP98939212A priority patent/EP1001964A4/fr
Priority to AU87687/98A priority patent/AU8768798A/en
Publication of WO1999006427A1 publication Critical patent/WO1999006427A1/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

Definitions

  • the invention relates to the discovery and characterization of the genes encoding Tango-78, Tango- 79, and Tango- 81.
  • the invention also features a host cell which includes an isolated nucleic acid molecule encoding Tango-78, Tango-79, or Tango-81, a nucleic acid vector (e.g., an expression vector; a vector which includes a regulatory element; a vector which includes a regulatory element selected from the group consisting of the cytomegalovirus hC V immediate early gene, the early promoter of SV40 adenovirus, the late promoter of SV40 adenovirus, the lac system, the trp system, the TAC system, the TRC system, the major operator and promoter regions of phage ⁇ , the control regions of fd coat protein, the promoter for 3-phosphoglycerate kinase, the promoters of acid phosphatase, and the promoters of the yeast c-mating factors; a vector which includes a regulatory element which directs tissue-specific expression; a vector which includes a reporter gene; a vector which includes a reporter gene selected from the group selected from the
  • the invention also features antibodies, e.g., monoclonal antibodies, that selectively binds to a polypeptide of the invention (Tango-78, Tango-79, or Tango-81) .
  • the invention also features a method for diagnosing a disorder associated with aberrant expression of Tango-78 the method including obtaining a biological sample from a patient and measuring Tango-78 expression in the biological sample, wherein increased or decreased Tango-78 expression in the biological sample compared to a control indicates that the patient suffers from a disorder associated with aberrant expression of Tango-78.
  • the invention also features a method for 5 diagnosing a disorder associated with aberrant expression of Tango-79, the method including obtaining a biological sample from a patient and measuring Tango-79 expression in the biological sample, wherein increased or decreased Tango-79 expression in the biological sample compared to 0 a control indicates that the patient suffers from a disorder associated with aberrant expression of Tango-79.
  • the invention also features a method for diagnosing a disorder associated with aberrant expression of Tango- 81, the method including obtaining a biological 5 sample from a patient and measuring Tango-81 expression in the biological sample, wherein increased or decreased Tango- 81 expression in the biological sample compared to a control indicates that the patient suffers from a disorder associated with aberrant expression of Tango- 81.
  • the invention encompasses isolated nucleic acid molecules encoding Tango-78, Tango-79, or Tango- 81 or a polypeptide fragment thereof; vectors containing these nucleic acid molecules; cells harboring recombinant DNA encoding Tango-78, Tango-79, or Tango-81; fusion proteins 5 which include Tango-78, Tango-79, or Tango-81; transgenic animals which express Tango-78, Tango-79, or Tango-81; recombinant knock-out animals which fail to express Tango-78, Tango-79, or Tango-81.
  • the invention encompasses nucleic acids that have
  • a nucleic acid sequence which is substantially identical to a given reference nucleic acid sequence is hereby defined as a nucleic acid having a sequence that has at least
  • the invention encompasses polypeptides that have a sequence that is substantially identical to the amino acid sequence of Tango-78, Tango-79, or Tango-81.
  • a polypeptide which is "substantially identical" to a given reference polypeptide is a polypeptide having a sequence that has at least 85%, preferably 90%, and more preferably 95%, 98%, 99% or more identity to the sequence of the given reference polypeptide sequence, e.g., the amino sequence of SEQ ID NO : 2 , SEQ ID NO: 4, or SEQ ID NO: 6.
  • the nucleic acid molecules of the invention can be inserted into vectors, as described below, which will facilitate expression of the insert.
  • the nucleic acid molecules and the polypeptides they encode can be used directly as diagnostic or therapeutic agents, or (in the case of a polypeptide) can be used to generate antibodies that, in turn, are therapeutically useful. Accordingly, expression vectors containing the nucleic acid molecules of the invention, cells transfected with these vectors, the polypeptides expressed, and antibodies generated (against either the entire polypeptide or an antigenic fragment thereof) are among the preferred embodiments.
  • a transformed cell is any cell into which (or into an ancestor of which) has been introduced, by means of recombinant DNA techniques, a nucleic acid encoding a polypeptide of the invention (e.g., a Tango-78, Tango-79, or Tango- 81 polypeptide) .
  • a polypeptide of the invention e.g., a Tango-78, Tango-79, or Tango- 81 polypeptide
  • An isolated nucleic acid molecule is a nucleic acid molecule that is separated from the 5' and 3' coding sequences with which it is immediately contiguous in the naturally occurring genome of an organism.
  • Isolated nucleic acid molecules include nucleic acid molecule which are not naturally occurring, e.g., nucleic acid molecules created by recombinant DNA techniques.
  • polypeptides of the invention can be prepared by recombinant gene expression, chemically synthesized, or purified from tissues in which they are naturally expressed using standard biochemical methods of purification.
  • a functional polypeptide is also considered within the scope of the invention if it serves as an antigen for production of antibodies that specifically bind to Tango-78, Tango-79, or Tango- 81. In many cases, functional polypeptides retain one or more domains present in the naturally-occurring form of the polypeptide .
  • the functional polypeptides may contain a primary amino acid sequence that has been modified from those disclosed herein. Preferably these modifications consist of conservative amino acid substitutions, as described herein.
  • the terms "protein” and "polypeptide” are used herein interchangably to describe any chain of amino acids, regardless of length or post-translational modification (for example, glycosylation or phosphorylation).
  • purified refers to a nucleic acid or peptide that is substantially free of cellular material, viral material, or culture medium when produced by recombinant DNA techniques, or chemical precursors or other chemicals when chemically synthesized.
  • Polypeptides or other compounds of interest are said to be “substantially pure” when they are within preparations that are at least 60% by weight (dry weight) the compound of interest.
  • the preparation is at least 75%, more preferably at least 90%, and most preferably at least 99%, by weight the compound of interest . Purity can be measured by any appropriate standard method, for example, by column chromatography, polyacrylamide gel electrophoresis, or HPLC analysis.
  • a particular polypeptide or nucleic acid molecule is said to have a specific percent identity to a reference polypeptide or nucleic acid molecule of a defined length, the percent identity is relative to the reference polypeptide or nucleic acid molecule.
  • a peptide that is 50% identical to a reference polypeptide that is 100 amino acids long can be a 50 amino acid polypeptide that is completely identical to a 50 amino acid long portion of the reference polypeptide. It might also be a 100 amino acid long polypeptide which is 50% identical to the reference polypeptide over its entire length.
  • many other polypeptides will meet the same criteria. The same rule applies for nucleic acid molecules .
  • non-identical positions are preferably, but not necessarily, conservative substitutions for the reference sequence.
  • Conservative substitutions typically include substitutions within the following groups: glycine and alanine; valine, isoleucine, and leucine; aspartic acid and glutamic acid; asparagine and glutamine; serine and threonine; lysine and arginine; and phenylalanine and tyrosine .
  • Sequence identity can be measured using sequence analysis software (for example, the Sequence Analysis Software Package of the Genetics Computer Group, University of Wisconsin Biotechnology Center, 1710 University Avenue, Madison, WI 53705) , with the default parameters as specified therein.
  • the invention also features antibodies, e.g., monoclonal, polyclonal, and engineered antibodies, which specifically bind Tango-78, Tango-79, or Tango-81.
  • specifically binds is meant an antibody that recognizes and binds to a particular antigen, e.g., a Tango-78, Tango-79, or Tango-81 polypeptide of the invention, but which does not substantially recognize or bind to other molecules in a sample, e.g., a biological sample, which includes the polypeptide.
  • the invention also features antagonists and agonists of Tango-78, Tango-79, or Tango-81 that can inhibit or enhance, respectively, one or more of the biological activities of Tango-78, Tango-79, or Tango- 81.
  • Suitable antagonists can include small molecules (i.e., molecules with a molecular weight below about 500) ; large molecules (i.e., molecules with a molecular weight above about 500) , antibodies that bind and "neutralize" Tango- 78, Tango-79, or Tango-81 (as described below) ; polypeptides which compete with a native form of Tango- 78, Tango-79, or Tango-81 for binding to a functional binding partner of the native protein; and nucleic acid molecules that interfere with transcription of Tango-78, Tango-79, or Tango-81 (for example, antisense nucleic acid molecules and ribozymes).
  • Agonists of Tango-78, Tango-79, or Tango-81 also include small and large molecules, and antibodies other than neutralizing antibodies.
  • the invention also features molecules which can increase or decrease the expression of Tango-78, Tango- 79, or Tango-81 (e.g., by influencing transcription or translation).
  • Small molecules i.e., molecules with a molecular weight below about 500
  • large molecules i.e., molecules with a molecular weight above about 500
  • nucleic acid molecules that can be used to inhibit the expression of Tango-78, Tango-79, or Tango-81 (for example, antisense and ribozyme molecules) or to enhance their expression (for example, molecules that bind to a Tango-78, Tango-79, or Tango-81 transcription regulatory sequence and increase transcription.
  • the invention encompasses methods for treating disorders associated with aberrant expression or activity of a protein of the invention (i.e., Tango-78, Tango-79, or Tango-81) .
  • the invention includes methods for treating disorders associated with excessive expression or activity of the protein. Such methods entail administering a compound which decreases the expression of the protein.
  • the invention also includes methods for treating disorders associated with insufficient expression or activity of a protein of the invention. These methods entail administering a compound which increases the expression or activity of the protein.
  • the nucleic acid molecules can be used as primers for diagnostic PCR analysis for the identification of gene mutations, allelic variations and regulatory defects in the Tango-78, Tango-79, or Tango-81 gene.
  • the present invention further provides for diagnostic kits for the practice of such methods.
  • the invention features methods of identifying compounds that modulate the expression or activity of a protein of the invention by assessing the expression or activity of the protein in the presence and absence of a selected compound. A difference in the level of expression or activity of the protein in the presence and absence of the selected compound indicates that the selected compound is capable of modulating expression or activity of the protein. Expression can be assessed either at the level of gene expression (e.g., by measuring mRNA) or protein expression by techniques that are well known to skilled artisans.
  • the isolated nucleic acid molecules of the invention encompass fragments that are not found as such in the natural state.
  • the invention encompasses recombinant molecules, such as those in which a nucleic acid molecule (for example, an isolated nucleic acid molecule encoding Tango-78, Tango-79, or Tango-81) is incorporated into a vector (for example, a plasmid or viral vector) or into the genome of a heterologous cell (or the genome of a homologous cell, at a position other than the natural chromosomal location) .
  • a nucleic acid molecule for example, an isolated nucleic acid molecule encoding Tango-78, Tango-79, or Tango-81
  • a vector for example, a plasmid or viral vector
  • Recombinant nucleic acid molecules and uses therefor are discussed further below.
  • the cDNA sequences described herein can be used to identify these nucleic acids, which include, for example, nucleic acids that encode homologous polypeptides in other species, and splice variants of the Tango-78, Tango-79, or Tango-81 gene in humans or other mammals. Accordingly, the invention features methods of detecting and isolating these nucleic acid molecules. Using these methods, a sample (for example, a nucleic acid library, such as a cDNA or genomic library) is contacted (or "screened") with a Tango-78, Tango-79, or Tango- 81-specific probe. The probe will selectively hybridize to nucleic acids encoding related polypeptides (or to complementary sequences thereof) .
  • a sample for example, a nucleic acid library, such as a cDNA or genomic library
  • the probe will selectively hybridize to nucleic acids encoding related polypeptides (or to complementary sequences thereof) .
  • nucleic acid sequence that can be used as a probe to screen a nucleic acid library and thereby detect nucleic acid molecules (within the library) that hybridize to the probe.
  • One single-stranded nucleic acid is said to hybridize to another if a duplex forms between them. This occurs when one nucleic acid contains a sequence that is the reverse and complement of the other (this same arrangement gives rise to the natural interaction between the sense and antisense strands of DNA in the genome and underlies the configuration of the "double helix") .
  • Complete complementarity between the hybridizing regions is not required in order for a duplex to form; it is only necessary that the number of paired bases is sufficient to maintain the duplex under the hybridization conditions used.
  • a second set of conditions that are considered “stringent conditions” are those in which hybridization is carried out at 50 °C in Church buffer (7% SDS, 0.5% NaHP0 4 , 1 M EDTA, 1% BSA) and washing is carried out at 50°C in 2X SSC.
  • the nucleic acid can form part of a hybrid gene encoding additional polypeptide sequences, for example, sequences that function as a marker or reporter.
  • marker or reporter genes include j ⁇ -lactamase, chloramphenicol acetyltransferase (CAT) , adenosine deaminase (ADA) , aminoglycoside phosphotransferase (neo r , G418 r ) , dihydrofolate reductase (DHFR) , hygromycin-B-phosphotransferase (HPH) , thymidine kinase (TK) , lacZ (encoding /3-galactosidase) , and xanthine guanine phosphoribosyltransferase (XGPRT) .
  • CAT chloramphenicol acetyltransferase
  • ADA adenosine deaminase
  • the expression systems that may be used for purposes of the invention include, but are not limited to, microorganisms such as bacteria (for example, E. coli and B . subtilis) transformed with recombinant bacteriophage DNA, plasmid DNA, or cosmid DNA expression vectors containing the nucleic acid molecules of the invention; yeast (for example, Saccharomyces and Pichia) transformed with recombinant yeast expression vectors containing the nucleic acid molecules of the invention; insect cell systems infected with recombinant virus expression vectors (for example, baculovirus) containing the nucleic acid molecules of the invention; plant cell systems infected with recombinant virus expression vectors (for example, cauliflower mosaic virus (CaMV) and tobacco mosaic virus (TMV) ) or transformed with recombinant plasmid expression vectors (for example, Ti plasmid) containing Tango-78, Tango-79, or Tango-81 nucleotide sequences; or mammalian cell systems
  • nucleic acid molecules of the invention are useful for diagnosis of disorders associated with aberrant expression of Tango-78, Tango-79, or Tango-81.
  • Tango-78, Tango-79, and Tango-81 nucleic acid molecules are also useful in genetic mapping and chromosome identification.
  • the invention also encompasses polypeptides that are functionally equivalent to Tango-78, Tango-79, or Tango-81. These polypeptides are equivalent to Tango-78, Tango-79, or Tango-81 in that they are capable of carrying out one or more of the functions of Tango-78, Tango-79, or Tango-81 in a biological system. Preferred Tango-78, Tango-79, or Tango-81 polypeptides have 20%, 40%, 50%, 75%, 80%, or even 90% of one or more of the biological activities of the full-length, mature human form of Tango-78, Tango-79, and Tango-81. Such comparisons are generally based on an assay of biological activity in which equal concentrations of the polypeptides are used and compared. The comparison can also be based on the amount of the polypeptide required to reach 50% of the maximal stimulation obtainable.
  • nucleic acid molecules of the invention can be made to generate variant genes that are better suited for expression in a selected host cell. For example, N-linked glycosylation sites can be altered or eliminated to achieve, for example, expression of a homogeneous product that is more easily recovered and purified from yeast hosts which are known to hyperglycosylate N-linked sites.
  • polypeptides of the invention can be chemically synthesized (for example, see Creighton, "Proteins: Structures and Molecular Principles,” W.H. Freeman & Co., NY, 1983), or, perhaps more advantageously, produced by recombinant DNA technology as described herein.
  • skilled artisans may consult Ausubel et al . ( supra) , Sambrook et al . ("Molecular Cloning, A Laboratory Manual,” Cold Spring Harbor Press, Cold Spring Harbor, NY, 1989) , and, particularly for examples of chemical synthesis Gait, M.J. Ed. ("Oligonucleotide Synthesis," IRL Press, Oxford, 1984) .
  • the present invention provides for transgenic animals that carry a Tango-78, Tango-79, or Tango-81 transgene in all their cells, as well as animals that carry a transgene in some, but not all of their cells. That is, the invention provides for mosaic animals.
  • the transgene can be integrated as a single transgene or in concatamers, e.g., head-to-head tandems or head-to-tail tandems.
  • the transgene can also be selectively introduced into and activated in a particular cell type (Lasko et al . , Proc . Natl . Acad. Sci . USA 89:6232, 1992).
  • the transgene also can be selectively introduced into a particular cell type, thus inactivating the endogenous Tango-78, Tango-79, or Tango-81 gene in only that cell type (Gu et al . , Science 265:103, 1984).
  • the regulatory sequences required for such a cell -type specific inactivation will depend upon the particular cell type of interest, and will be apparent to those of skill in the art. These techniques are useful for preparing "knock outs" lacking a functional gene.
  • Anti-Tango-78 , Tango-79, or Tango-81 Antibodies Human Tango-78, Tango-79, and Tango-81 polypeptides can be used to raise antibodies useful in the invention; such polypeptides can be produced by recombinant techniques or synthesized (see, for example, "Solid Phase Peptide Synthesis," supra ; Ausubel et al . , supra) .
  • the peptides can be coupled to a carrier protein, such as KLH, as described in Ausubel et al . , supra, mixed with an adjuvant, and injected into a host mammal.
  • Antibodies can be purified by peptide antigen affinity chromatography.
  • Monoclonal antibodies which are homogeneous populations of antibodies to a particular antigen, can be prepared using the Tango-78, Tango-79, or Tango-81 polypeptides described above and standard hybridoma technology (see, for example, Kohler et al . , Nature 256:495, 1975; Kohler et al . , Eur. J. Immunol . 6:511, 1976; Kohler et al . , Bur. J “ . Immunol. 6:292, 1976; Hammerling et al . , "Monoclonal Antibodies and T Cell
  • monoclonal antibodies can be obtained by any technique that provides for the production of antibody molecules by continuous cell lines in culture such as described in Kohler et al . , Nature 256:495, 1975, and U.S. Patent No. 4,376,110; the human B-cell hybridoma technique (Kosbor et al . , Immunology Today 4:72, 1983; Cole et al . , Proc . Natl . Acad . Sci . USA 80:2026, 1983), and the EBV-hybridoma technique (Cole et al . , "Monoclonal Antibodies and Cancer Therapy, " Alan R. Liss, Inc., pp. 77-96, 1983).
  • Such antibodies can be of any immunoglobulin class including IgG, IgM, IgE, IgA, IgD and any subclass thereof.
  • the hybridoma producing the mAb of this invention may be cultivated in vi tro or in vivo .
  • the ability to produce high titers of mAbs in vivo makes this a particularly useful method of production.
  • polyclonal or monoclonal antibodies are tested for specific Tango-78, Tango-79, or Tango-81 recognition by Western blot or immunoprecipitation analysis by standard methods, e.g., as described in Ausubel et al . , supra .
  • Antibodies that specifically recognize and bind to Tango-78, Tango-79, or Tango-81 are useful in the invention.
  • such antibodies can be used in an immunoassay to monitor the level of
  • chimeric antibodies In addition, techniques developed for the production of "chimeric antibodies" (Morrison et al . , Proc . Na tl . Acad . Sci . USA, 81:6851, 1984; Neuberger et al., Nature, 312:604, 1984; Takeda et al . , Nature, 314:452, 1984) by splicing the genes from a mouse antibody molecule of appropriate antigen specificity together with genes from a human antibody molecule of appropriate biological activity can be used.
  • a chimeric antibody is a molecule in which different portions are derived from different animal species, such as those having a variable region derived from a murine mAb and a human immunoglobulin constant region.
  • Antibodies to Tango-78, Tango-79, or Tango- 81 can, in turn, be used to generate anti-idiotype antibodies that resemble a portion of the protein using techniques well known to those skilled in the art (see, e.g.,
  • anti-Tango- 78, Tango-79, or Tango-81 antibodies may be employed, for example, by utilizing pre-packaged diagnostic kits comprising at least one specific Tango- 78, Tango-79, or Tango-81 antibody reagent described herein, which may be conveniently used, for example, in clinical settings, to diagnose patients exhibiting symptoms disorders associated with abberent expression of Tango-78, Tango-79, or Tango-81.
  • Antisense Nucleic Acids Treatment regimes based on an "antisense" approach involve the design of oligonucleotides (either DNA or RNA) that are complementary to Tango-78, Tango-79, or Tango-81 mRNA.
  • Oligonucleotides that are complementary to the 5' end of the message should work most efficiently at inhibiting translation.
  • sequences complementary to the 3' untranslated sequences of mRNAs recently have been shown to be effective at inhibiting translation of mRNAs as well (Wagner, Nature 372:333, 1984).
  • Oligonucleotides complementary to either the 5' or 3 ' non-translated, non-coding regions of the gene could be used in an antisense approach to inhibit translation of endogenous mRNA.
  • Oligonucleotides complementary to the 5' untranslated region of the mRNA should include the complement of the AUG start codon.
  • control oligonucleotide is of approximately the same length as the test oligonucleotide and that the nucleotide sequence of the oligonucleotide differs from the antisense sequence no more than is necessary to prevent specific hybridization to the target sequence .
  • the invention also features polypeptides which interact with Tango-78, Tango-79, or Tango-81.
  • Any method suitable for detecting protein-protein interactions may be employed for identifying transmembrane proteins, intracellular, or extracellular proteins that interact with Tango-78, Tango-79, or Tango- 81.
  • traditional methods which may be employed are co-immunoprecipitation, cross-linking and co-purification through gradients or chromatographic columns of cell lysates or proteins obtained from cell lysates and the use of Tango-78, Tango-79, or Tango-81 to identify proteins in the lysate that interact with Tango- 78, Tango-79, or Tango-81.
  • Liquid preparations for oral administration may take the form of, for example, solutions, syrups or suspensions, or they may be presented as a dry product for constitution with water or other suitable vehicle before use.
  • Such liquid preparations may be prepared by conventional means with pharmaceutically acceptable additives such as suspending agents (for example, sorbitol syrup, cellulose derivatives or hydrogenated edible fats) ; emulsifying agents (for example, lecithin or acacia) ; non-aqueous vehicles (for example, almond oil, oily esters, ethyl alcohol or fractionated vegetable oils) ; and preservatives (for example, methyl or propyl- p-hydroxybenzoates or sorbic acid) .
  • the preparations may also contain buffer salts, flavoring, coloring and sweetening agents as appropriate.
  • Preparations for oral administration may be suitably formulated to give controlled release of the active compound.
  • the compounds may also be formulated in rectal compositions such as suppositories or retention enemas, for example, containing conventional suppository bases such as cocoa butter or other glycerides .
  • the compounds may also be formulated as a depot preparation.
  • Such long acting formulations may be administered by implantation (for example subcutaneously or intramuscularly) or by intramuscular injection.
  • the compounds may be formulated with suitable polymeric or hydrophobic materials (for example as an emulsion in an acceptable oil) or ion exchange resins, or as sparingly soluble derivatives, for example, as a sparingly soluble salt .
  • administration can be parenteral, intravenous, subcutaneous, intramuscular, intracranial , intraorbital , opthalmic, intraventricular, intracapsular, intraspinal, intracisternal, intraperitoneal, transmucosal, or oral.
  • the modulatory compound can be formulated in various ways, according to the corresponding route of administration.
  • liquid solutions can be made for ingestion or injection; gels or powders can be made for ingestion, inhalation, or topical application. Methods for making such formulations are well known and can be found in, for example, "Remington's Pharmaceutical Sciences.” It is expected that the preferred route of administration will be intravenous.

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Abstract

L'invention concerne des polypeptides Tango-78, Tango-79 et Tango-81, des molécules d'acide nucléique codant Tango-78, Tango-79 et Tango 81, et l'utilisation de ces derniers.
PCT/US1998/016241 1997-08-04 1998-08-04 Molecules d'acide nucleique tango-78, tango-79 et tango-81 WO1999006427A1 (fr)

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Application Number Priority Date Filing Date Title
CA002299276A CA2299276A1 (fr) 1997-08-04 1998-08-04 Molecules d'acide nucleique tango-78, tango-79 et tango-81
JP2000505183A JP2001512003A (ja) 1997-08-04 1998-08-04 Ｔａｎｇｏ−７８、Ｔａｎｇｏ−７９およびＴａｎｇｏ−８１ポリペプチド、Ｔａｎｇｏ−７８、Ｔａｎｇｏ−７９およびＴａｎｇｏ−８１をコードする核酸分子ならびにそれらの使用
EP98939212A EP1001964A4 (fr) 1997-08-04 1998-08-04 Molecules d'acide nucleique tango-78, tango-79 et tango-81
AU87687/98A AU8768798A (en) 1997-08-04 1998-08-04 Tango-78, tango-79, and tango-81 nucleic acid molecules and polypeptides

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US5464597P 1997-08-04 1997-08-04
US60/054,645 1997-08-04

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WO2000066778A1 (fr) * 1999-04-30 2000-11-09 Human Genome Sciences, Inc. Genes et polypeptides de pituitrone
WO2002016579A2 (fr) * 2000-08-24 2002-02-28 Eli Lilly And Company Acides nucleiques, vecteurs, cellules hotes, polypeptides et utilisations de ces derniers
WO2002083914A2 (fr) * 2001-04-17 2002-10-24 Pe Corporation (Ny) Proteines humaines secretees isolees, molecules d'acide nucleique codant des proteines humaines secretees et utilisations associees
EP1254269A1 (fr) * 2000-02-03 2002-11-06 Hyseq Inc. Procedes et matieres lies aux polypeptides et aux polynucleotides du type molecule de guidage neuronal (du type ngm)
EP1255771A1 (fr) * 2000-02-14 2002-11-13 Smithkline Beecham Corporation Nouveaux composes
US7034132B2 (en) 2001-06-04 2006-04-25 Anderson David W Therapeutic polypeptides, nucleic acids encoding same, and methods of use
US7223558B2 (en) * 2001-07-11 2007-05-29 Bristol-Myers Squibb Company Polynucleotides encoding three novel human cell surface proteins with leucine rich repeats and immunologobulin folds, BGS2, 3, and 4 and variants thereof
US7785829B2 (en) 2003-03-19 2010-08-31 Biogen Idec Ma, Inc. Nogo receptor binding protein
US8058406B2 (en) 2008-07-09 2011-11-15 Biogen Idec Ma Inc. Composition comprising antibodies to LINGO or fragments thereof
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WO2002016579A3 (fr) * 2000-08-24 2002-11-28 Lilly Co Eli Acides nucleiques, vecteurs, cellules hotes, polypeptides et utilisations de ces derniers
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WO2002083914A2 (fr) * 2001-04-17 2002-10-24 Pe Corporation (Ny) Proteines humaines secretees isolees, molecules d'acide nucleique codant des proteines humaines secretees et utilisations associees
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US7705134B2 (en) * 2001-07-11 2010-04-27 Bristol-Myers Squibb Company Antibodies that bind to BGS-4
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US8551476B2 (en) 2005-07-08 2013-10-08 Biogen Idec Ma Inc. SP35 antibodies and uses thereof
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US8128926B2 (en) 2007-01-09 2012-03-06 Biogen Idec Ma Inc. Sp35 antibodies and uses thereof
US8058406B2 (en) 2008-07-09 2011-11-15 Biogen Idec Ma Inc. Composition comprising antibodies to LINGO or fragments thereof
US8425910B2 (en) 2008-07-09 2013-04-23 Biogen Idec Ma Inc. Composition comprising antibodies to LINGO or fragments thereof
US9745375B2 (en) 2008-07-09 2017-08-29 Biogen Ma Inc. Compositions comprising antibodies to LINGO or fragments thereof
US9796780B2 (en) 2012-05-14 2017-10-24 Biogen Ma Inc. LINGO-2 antagonists for treatment of conditions involving motor neurons
US10435467B2 (en) 2015-01-08 2019-10-08 Biogen Ma Inc. LINGO-1 antagonists and uses for treatment of demyelinating disorders

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EP1001964A1 (fr) 2000-05-24
JP2001512003A (ja) 2001-08-21
CA2299276A1 (fr) 1999-02-11
AU8768798A (en) 1999-02-22
EP1001964A4 (fr) 2003-04-23

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